Enfermedades autoinmunes y manifestaciones psiquiátricas

42

Transcript of Enfermedades autoinmunes y manifestaciones psiquiátricas

Page 1: Enfermedades autoinmunes y manifestaciones psiquiátricas

Enfermedades autoinmunes

Enfermedades del tejido conectivo

Sistemas y oacuterganos

Siacutentomas psiquiaacutetricos y neuroloacutegicos

Una de las causas mas comunes son tipo vascular (cambios inflamatorios tromboacuteticos) inmunoloacutegicos y ateroescleroacuteticos

Forma de siacutendrome ndash diferente presentacioacuten

Resultados de enfermedad o tratamiento (esteroides o agentes bioloacutegicos)

Manifestaciones psiquiaacutetricas Mas comunes

Cambios de comportamiento

Suentildeo

Inestabilidad emocional

Siacutentomas neuropsiquiaacutetricos son mas vistos en LES (hasta 80 ) sobre todo cuando coexiste con siacutendrome antifosfoliacutepidos

Autoanticuerpos

Problema cliacutenico separado

Au

toan

ticu

erp

os

Lupus inducido por drogas

Tra

tam

ien

toe

nfe

rmed

ad Primario

Secundario

La prevalencia de los siacutentomas psiquiaacutetricos depende y difiere del involucro del SNC SNP y autonoacutemico

Maacutes comunes disfuncioacuten cognitiva progresiva inestabilidad emocional trastornos del suentildeo y del afecto deacuteficits en memoria despersonalizacioacuten desrealizacioacuten depresioacuten ansiedad alucinaciones y delirios de referencia

Una de las principales afecciones primarias causales es de tipo vascular de patogeacutenesis multifactorial principalmente tromboinflamatoria e inmuneinflamatoria

Involucro vascular

bull Inflamacioacuten croacutenica (aa)

bull Lesiones subcliacutenicasateroescleroacuteticas

AutoanicuerposCitocinas

proinflamatorias

Ateroesclerosis acelerada

LES (30-40)

Stroke en 20a 30 de AI Complicacioacuten mas seria y una de las principales causas de muerteStroke isqueacutemicos raros silentes no especiacuteficos deterioro cognitivo progresivo

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 2: Enfermedades autoinmunes y manifestaciones psiquiátricas

Manifestaciones psiquiaacutetricas Mas comunes

Cambios de comportamiento

Suentildeo

Inestabilidad emocional

Siacutentomas neuropsiquiaacutetricos son mas vistos en LES (hasta 80 ) sobre todo cuando coexiste con siacutendrome antifosfoliacutepidos

Autoanticuerpos

Problema cliacutenico separado

Au

toan

ticu

erp

os

Lupus inducido por drogas

Tra

tam

ien

toe

nfe

rmed

ad Primario

Secundario

La prevalencia de los siacutentomas psiquiaacutetricos depende y difiere del involucro del SNC SNP y autonoacutemico

Maacutes comunes disfuncioacuten cognitiva progresiva inestabilidad emocional trastornos del suentildeo y del afecto deacuteficits en memoria despersonalizacioacuten desrealizacioacuten depresioacuten ansiedad alucinaciones y delirios de referencia

Una de las principales afecciones primarias causales es de tipo vascular de patogeacutenesis multifactorial principalmente tromboinflamatoria e inmuneinflamatoria

Involucro vascular

bull Inflamacioacuten croacutenica (aa)

bull Lesiones subcliacutenicasateroescleroacuteticas

AutoanicuerposCitocinas

proinflamatorias

Ateroesclerosis acelerada

LES (30-40)

Stroke en 20a 30 de AI Complicacioacuten mas seria y una de las principales causas de muerteStroke isqueacutemicos raros silentes no especiacuteficos deterioro cognitivo progresivo

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 3: Enfermedades autoinmunes y manifestaciones psiquiátricas

Autoanticuerpos

Problema cliacutenico separado

Au

toan

ticu

erp

os

Lupus inducido por drogas

Tra

tam

ien

toe

nfe

rmed

ad Primario

Secundario

La prevalencia de los siacutentomas psiquiaacutetricos depende y difiere del involucro del SNC SNP y autonoacutemico

Maacutes comunes disfuncioacuten cognitiva progresiva inestabilidad emocional trastornos del suentildeo y del afecto deacuteficits en memoria despersonalizacioacuten desrealizacioacuten depresioacuten ansiedad alucinaciones y delirios de referencia

Una de las principales afecciones primarias causales es de tipo vascular de patogeacutenesis multifactorial principalmente tromboinflamatoria e inmuneinflamatoria

Involucro vascular

bull Inflamacioacuten croacutenica (aa)

bull Lesiones subcliacutenicasateroescleroacuteticas

AutoanicuerposCitocinas

proinflamatorias

Ateroesclerosis acelerada

LES (30-40)

Stroke en 20a 30 de AI Complicacioacuten mas seria y una de las principales causas de muerteStroke isqueacutemicos raros silentes no especiacuteficos deterioro cognitivo progresivo

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 4: Enfermedades autoinmunes y manifestaciones psiquiátricas

La prevalencia de los siacutentomas psiquiaacutetricos depende y difiere del involucro del SNC SNP y autonoacutemico

Maacutes comunes disfuncioacuten cognitiva progresiva inestabilidad emocional trastornos del suentildeo y del afecto deacuteficits en memoria despersonalizacioacuten desrealizacioacuten depresioacuten ansiedad alucinaciones y delirios de referencia

Una de las principales afecciones primarias causales es de tipo vascular de patogeacutenesis multifactorial principalmente tromboinflamatoria e inmuneinflamatoria

Involucro vascular

bull Inflamacioacuten croacutenica (aa)

bull Lesiones subcliacutenicasateroescleroacuteticas

AutoanicuerposCitocinas

proinflamatorias

Ateroesclerosis acelerada

LES (30-40)

Stroke en 20a 30 de AI Complicacioacuten mas seria y una de las principales causas de muerteStroke isqueacutemicos raros silentes no especiacuteficos deterioro cognitivo progresivo

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 5: Enfermedades autoinmunes y manifestaciones psiquiátricas

Involucro vascular

bull Inflamacioacuten croacutenica (aa)

bull Lesiones subcliacutenicasateroescleroacuteticas

AutoanicuerposCitocinas

proinflamatorias

Ateroesclerosis acelerada

LES (30-40)

Stroke en 20a 30 de AI Complicacioacuten mas seria y una de las principales causas de muerteStroke isqueacutemicos raros silentes no especiacuteficos deterioro cognitivo progresivo

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 6: Enfermedades autoinmunes y manifestaciones psiquiátricas

Siacutentomas neuropsiquiaacutetricos

ES (siacutentomas SNP)

AR (Disfuncioacuten)

LES (Criteriosimagen

cliacutenica)

Casi todas AI

Inmunosupresioacuten

Autoinmunizacioacuten

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 7: Enfermedades autoinmunes y manifestaciones psiquiátricas

Articulaciones deformidades

05-1

AR

bull Muerte temprana

bull Disfuncioacuten progresiva

bull Manifestaciones extra-articulares y sisteacutemicas

bull 2x-3x en mujeres

bull 4 y 5 deacutecada

bull AIinflamatoria

bull Mas comuacuten de articulaciones

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 8: Enfermedades autoinmunes y manifestaciones psiquiátricas

Cambios neuroloacutegicos

bull SNP

bull Compresioacuten

bull Inflamacioacuten

bull Paresia

Factores psicosociales

bull Adaptacioacuten negativa de cronicidad

bull Depresioacuten y ansiedad (14 a 42)

bull Estresores

bull Suentildeo

Depresioacuten

bull Fem AR con suicidio (90 depresioacuten)

bull AR mayor PG

bull Depresioacuten (dolor articulaciones pobre funcioacuten)

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 9: Enfermedades autoinmunes y manifestaciones psiquiátricas

Estresores por AR croacutenica

Limitacioacuten actividadfuncional Econoacutemicos (peacuterdida $costos ) Cambios apariencia

Relaciones sociales alteradas (50) (comunicacioacutencomportamiento)

Relacioacuten pareja (empeore o module)

Incremento estresores (rigidez dolor global y respuesta AI alterada)

Eje HPA (estresores y actividad de AR)

Distorsiones cognitivas (impotencia aprendida)

Estrategias coping(educacioacutenhabilidades)

(lidiarprevenir)

Modificadores bioloacutegicos de la enfermedad ($$$ remisioacuten eficacia calidad problemas psicosociales)

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 10: Enfermedades autoinmunes y manifestaciones psiquiátricas

LES

AI

bull Amplio espectro de manifestaciones cliacutenicas

bull Prevalencia 51 por 100000 en USA

Poblacioacuten

bull F 91 H

bull Ancianos serositis involucro pulmonar sicca manifestacionesmuacutesculo esqueleacuteticas

Muerte

bull 90 viven maacutes de 5 antildeos

bull Etapas tempranas infecciones

bull Etapas tardiacuteas complicaciones cardiovasculares por ateroesclerosis

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 11: Enfermedades autoinmunes y manifestaciones psiquiátricas

American College of Rheumatology

19 de SNC y SNP

Trastornos psiquiaacutetricos agudos ocurren dentro de los 2 antildeos del diagoacutestico

SNC

Meningitis aseacuteptica enfermedad cerebrovascular siacutendrome desmielinizante

cefalea trastorno del movimiento mieloptiacutea epilepsia confuscioacuten ansiedad

cognitivo psicosis y afecto

Neuropsiquiaacutetricos LES (NPSLE)

LES criterios

Diagnoacutestico de exclusioacuten Otras causas de los siacutentomas infeccioacuten electroliacuteticas renales medicamentos masas embolia psiquiaacutetrico primaria

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 12: Enfermedades autoinmunes y manifestaciones psiquiátricas

Cerebritis luacutepica

Base orgaacutenicaAnticuerpos antineurona

Anticuerpos antirribosoma

(psicosis y depresioacuten)

Siacutentomas neuropsiquiaacutetricos

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 13: Enfermedades autoinmunes y manifestaciones psiquiátricas

Prevalencia de manifestaciones neuropsiquiaacutetricas

+-

bull Cognitiva cefalea afecto enfermedad cerebrovascular convulsiones polineuropatiacutea ansiedad y psicosis

Psicosis

bull Orgaacutenica 35-5 en LES en el primer antildeo

bull Pensamiento bizarro con alucinaciones y delirios y puede ser fluctuante sobre todo en PM

bull Otros sx atencioacuten agitacioacuten comportamiento agresivo

bull Pueden ser por esteroides (auditivas) o por LES SNC (taacutectiles y visuales)

bull Psicosis por LES reponde bien a esteroides 2-3 semanas citotoacutexicos

bull Mientras tx con antipsicoacuteticos

Procesos psicoloacutegicos funcionales

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 14: Enfermedades autoinmunes y manifestaciones psiquiátricas

Disfuncioacuten cognitivabull Memoria a corto y largo plazo

bull Juicio abstraccioacuten afasia apraxia

bull Agnosia y cambios personalidad

Siacutendrome orgaacutenico mental

bull 21 al 80

bull Anticuerpos relacioacuten SNC

bull Condiciones asociadas hipertensioacuten o muacuteltiples infartos

bull Maacutes comuacuten e pacientes con LES activo en tx con esteroides

bull Asociada a historia de dantildeo en SNC

bull Asociada a actividad de enfermedad (efecto de SNC difuso y transitorio)

Memoria

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 15: Enfermedades autoinmunes y manifestaciones psiquiátricas

Tratamiento cognitivo Basado en la etiologiacutea

Medicamentos disminuir o quitar

Ab antifosfoliacutepidos anticoagulantes

Ab antineurona esteroides pocas semanas

Reentrenamiento y soporte psicosocial

Aspirina en ancianos y riesgo casdiovascular

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 16: Enfermedades autoinmunes y manifestaciones psiquiátricas

Demencia Memoria

Abstraccioacuten

Tareas diarias

Decisioacuten e impulsividad

Asocia a pequentildeos strokes muacuteltiples por anticueposantifosfoliacutepidos

Antipalpudicos pueden tener efecto protector

Pueden ser por lesiones vasculares isqueacutemicas por ateroesclerosis temprana

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 17: Enfermedades autoinmunes y manifestaciones psiquiátricas

Parestesiascefalea

Cambios aacutenimo

Maniacutea

Ansiedaddepresioacuten

Agorafobiafobia social

Fobia

Cognitivo (memoriaafasiaorientacioacuten

espacial)

Manifestaciones psiquiaacutetricas secundarias

Depresioacuten

Ansiedad

Comportamiento maniacutea

like

Funcionales

Interaccioacuten px-meacutedicoFrustracioacuten por proceso dx largo

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 18: Enfermedades autoinmunes y manifestaciones psiquiátricas

Depresioacuten Manifestacioacuten psiquiaacutetrica maacutes comuacuten

Usualmente comienzan de manera aguda como reaccioacuten a cronicidad y limitaciones en estilo de vida

Despueacutes de una exacerbacioacuten aguda algunos pacientes pueden presentar siacutentomas de ansiedad junto o en vez de los depresivos

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 19: Enfermedades autoinmunes y manifestaciones psiquiátricas

Ansiedad Por las posibles consecuencias de la enfermedad

Manifestada como siacutentomas somaacuteticos

Puede deteriorar en comportamiento TOC like fobia hipocondriacutea insomnio y aislamiento

Raramente se desarrolla maniacutea o trastorno orgaacutenico de la personalidad (altas dosis)

Labilidad emocional desinhibicioacuten sexual verborrea religiosidad y agresividad

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 20: Enfermedades autoinmunes y manifestaciones psiquiátricas

Siacutendrome antifosfoliacutepidos Siacutentomas neuropsiquiaacutetricos similares a LES

Ab antifosfoliacutepidos hasta 50 en LES

SAP primario trombofilia adquirida mas comuacuten trombosis arterial y venosa abortos espontaacuteneos y otras complicaciones embarazo

Ab antifosfoliacutepidos Anticoagulante luacutepico anticardiolipina y anti glicoproteiacutena I beta 2

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 21: Enfermedades autoinmunes y manifestaciones psiquiátricas

SNC

bull Stroke

bull Corea

bull Mielitis transversa

bull Demencia progresiva

Psiquiaacutetricos

bull Cognitivos

bull Amnesia generalizada

bull Lesiones vasculares en sustancia blanca

bull Coexistir con liacutevedoreticularis

EM

bull Algunos pude haber AB AF

bull Difiacutecil diferenciar de EM lesiones

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 22: Enfermedades autoinmunes y manifestaciones psiquiátricas

bull Sicca

bull Sx psiquiaacutetricos parecidos a EM

bull Anti-Ro

bull Ansiedad 48

bull Depresioacuten 23Sjoumlgren

bull Rara lesiones en piel tejido subcutaacuteneo u oacuterganos internos

bull Morfologiacutea de vasos (Raynaud hipertensioacuten pulmonar arterial)

bull Siacutentomas neuropsiquiaacutetricos son raros (SNP)(depresioacuten por cronicidad)

Esclerosis sisteacutemica

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 23: Enfermedades autoinmunes y manifestaciones psiquiátricas

Vasculitis sisteacutemicas

bullSNP

bullVasculitis necroacutetica granulomatosa

bullAsma bronquial y eosinofilia perifeacuterica

bullPsicosis y orientacioacuten

bullDiversa

bullTamantildeo de vasos

bullGrupo heterogeacuteneo

bullRaras

bullPrimarias o secundarias

bullPsicosis en joacutevenes

bullSNC por hipertensioacuten arterial

bull70 sx neuroloacutegicos neuropatiacutea perifeacuterica

bullVasculitis av

bullPersonalidad depresioacuten y demencia

bull20 meningitis y encefalitis aseacuteptica Arteritis y trombosis senos venosos

BehccediletPoliarteritis

nodosa

Churg-StraussSintomatologiacutea

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 24: Enfermedades autoinmunes y manifestaciones psiquiátricas

Complicaciones psiquiaacutetricas debido al tratamiento

bull Prolongado altas dosis

bull Reversibles y moderadas al disminuir o quitar

Esteroides

bull Maniacutea hipomaniacutea

bull Labilidaddepresioacuten

bull Psicosisdelirium

bull Confusioacutendesorientacion

bull Cognitivosmemoria

Psiquiaacutetricasbull Suentildeo (dosis divididas)

bull Acatisia

bull Ancianos (riesgo)

bull Inicio (agitacioacuten euforia hipomaniacutea)

Depresioacuten despueacutes de terapia larga sobre todo en historia familiar de esta y OHMayor severidad a pocos diacuteas con dosis superiores a 20mg de prednisona10 necesidad de reduccioacuten y antipsicoacuteticosPsicosis aumenta en LES con hipoalbuminemia

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 25: Enfermedades autoinmunes y manifestaciones psiquiátricas

Esteroides Psicosis diferenciar de glucocorticoide vs LES en altas

dosis

Bajas dosis memoria riesgo elevado ancianos

1 alteraciones cognitivas persistentes

Riesgo suicida elevado

Pseudotumor cerebri raro

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 26: Enfermedades autoinmunes y manifestaciones psiquiátricas

Antipaluacutedicos

Cloroquina e hidroxicloroquina

Moderados y transitorios

Cefalea mareo

Raros labilidad agitacioacuten insomnio pesadillas ansiedad fatiga delirios y alucinaciones

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 27: Enfermedades autoinmunes y manifestaciones psiquiátricas

Faacutermacos Siacutentesis de autoanticuerpos por faacutermacos

Mayor parte no desarrolla enfermedad autoinmune

Lupus inducido por faacutermacos sujetos sin historia de LES que desarrollan ab antinucleares + sintomas de LES despues de exposicioacuten adecuada a medicamento sintomas se resuelven al descontinuar

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 28: Enfermedades autoinmunes y manifestaciones psiquiátricas

Fiebre Rash

Artritis Mialgias

SerositisHematoloacutegicasrenalesSNC

raras

An antihistonas en 95Hipocomplementenemia y ab anti-DNA son poco comunes

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 29: Enfermedades autoinmunes y manifestaciones psiquiátricas

Medicamentos

bull Riesgo bajo

bull Clorpromazina

bull Perfenazina

bull Litio

Tratamiento

bull Descontinuar

bull Antipaluacutedicos

bull Glucocorticoides

bull Aines

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 30: Enfermedades autoinmunes y manifestaciones psiquiátricas

Hipertiroiddismo Graveacutes AI

Causa mas comuacuten de hipertiroidismo

Oftalmopatiacutea psiquiaacutetricos

Hiperactividad del sistema adreneacutergico

Antagonistas beta adreneacutergicos y antitiroideos

Faacutermacos psicotroacutepicos Necesarios = eutiroideos

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 31: Enfermedades autoinmunes y manifestaciones psiquiátricas

Manifestaciones psiquiaacutetricas del hipertiroidismo

Robert Graves

1835

Bocio palpitaciones disfuncioacuten nerviosa y siacutentomas oculares

Discretos trastornos psiquiaacutetricos no psicoacuteticos

SecundarioTP antes de Graveacutes

(comoacuterbido)

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 32: Enfermedades autoinmunes y manifestaciones psiquiátricas

Hipertiroidismo y siacutentomas psiquiaacutetricos Depresioacuten

Ansiedad

Hipertiroidismo subcliacutenico (similar escalas)

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 33: Enfermedades autoinmunes y manifestaciones psiquiátricas

The presence of antithyroid antibodies in patientswith affective and nonaffective psychiatricdisorders

John J Haggerty Jr 1 Dwight L Evans1 2 Robert N Golden1 Cort A Pedersen1 Jeffrey S Simon3 Charles B Nemeroff4

Biological Psychiatry

Volume 27 Issue 1 1 January 1990 Pages 51ndash60

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 34: Enfermedades autoinmunes y manifestaciones psiquiátricas

Abstract We determined the frequency of antihyroglobulin and antimicrosomal

antibodies in 173 consecutively admitted psychiatric inpatients (We found antihydroid antibodies in 8 (565) of patients with DSM-III major depression 13 (431) with bipolar disorder and in 0 (04) of those with schizoaffective disorder) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole The overall frequency of positive antihydroid antibody titers in patients with DSM-III affective disorder 9 (999) did not differ from that in patients with nonaffective disorders 10 (768) However patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder even in the absence of lithium exposure However as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 35: Enfermedades autoinmunes y manifestaciones psiquiátricas

disordersMuumlller N Ackenheil M

1 Parallel to the current rapid development of new immunological methods immune mechanisms are gaining more importance for our understanding of psychiatric disorders The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system 2 The topical literature dealing with the interactions of immune system neurotransmitters psychological processes and psychiatric disorders especially in relation to cytokines is reviewed 3 An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described Cytokines actively transported into the CNS play a key role in this immune activation It was recently observed that cytokines activate astrocytes and microglia cells which in turn produce cytokines by a feedback mechanism Moreover they strongly influence the dopaminergic noradrenergic and serotonergic neurotransmission 4 There are indications that the cascade of cytokines can be activated by neuronal processes These findings close a theoretical gap between stress and its influence on immunity Psychomotor sickness behavior and sleep are related to IL-1 disturbances of memory and cognitive impairment are to IL-2 in part also to TNF-alpha The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia and IL-6 on depressive disorders 5 Although single cytokines most likely do not have a specificity for certain psychiatric disorders a characteristic pattern of cytokine actions in the CNS including influences of the cytokines on the blood-brain barrier seems to play a role in psychiatric disorders This may have therapeutic implications for the future

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 36: Enfermedades autoinmunes y manifestaciones psiquiátricas

Volume 51 Issue 4 15 February 2002 Pages 305ndash311

Abstract Background We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and

thyroid failure in outpatients with bipolar disorder compared with two control groups Methods The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226) a

population control group (n = 252) and psychiatric inpatients of any diagnosis (n = 3190) were measured Thyroid failure was defined as a raised thyroid stimulating hormone level previously diagnosed hypothyroidism or both Subjects were compared with attention to age gender and exposure to lithium

Results The TPO-Abs were more prevalent in bipolar patients (28) than population and psychiatric controls (3ndash18) The presence of TPO-Abs in bipolar patients was associated with thyroid failure but not with age gender mood state rapid cycling or lithium exposure Thyroid failure was present in 17 of bipolar patients and more prevalent in women It was associated with lithium exposure especially in the presence of TPO-Abs but not with current rapid cycling although an association may have been masked by thyroid hormone replacement

Conclusions Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment These variables appear to be independent risk factors for the development of hypothyroidism especially in women with bipolar disorder

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 37: Enfermedades autoinmunes y manifestaciones psiquiátricas

nelli Aa middot Fiore Eb middot Chiovato Lb middot Perugi Ga middotMarazziti Da

Abstract Several studies have underlined the high prevalence of psychiatric

symptoms and disorders in thyroid diseases The aim of this study was to evaluate the prevalence of psychiatric disorders in 93 inpatients affected by different thyroid diseases during their lifetimes by means of a standardized instrument ie the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised Upjohn Version (SCID-UP-R) The results showed higher rates of panic disorder simple phobia obsessive-compulsive disorder major depressive disorder bipolar disorder and cyclothymia in thyroid patients than in the general population These findings would suggest that the co-occurrence of psychiatric and thyroid diseases may be the result of common biochemical abnormalities

Neuropsychobiology 199838222ndash225

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65

Page 38: Enfermedades autoinmunes y manifestaciones psiquiátricas

with bipolar disorderRoos C Padmosa

Background In a previous study we reported an increased prevalence of thyroperoxidase antibodies (TPOA) in

patients with bipolar disorder Here we report the prevalence of other organ-specific autoantibodies HK adenosine triphosphatase (ATPA) glutamic acid decarboxylase-65 (GAD65A) and GAD-67 (GAD67A)

Methods ATPA GAD65A and GAD67A were determined (via a commercially available enzyme linked

immunosorbent assay for ATPA and a standardized radio immunoassays for GAD65A and GAD67A)in the sera of 239 patients with DSM-IV bipolar disorder in 74 patients with DSM-IV schizophrenia and in 220 healthy control subjects

Results The positivity prevalences for ATPA and GAD65A (but not GAD67A) were elevated in bipolar patients

compared with those in healthy control subjects (117 vs 61 and 113 vs 26 respectively p lt05) Schizophrenia patients did not show such statistically higher prevalence The elevated prevalence of ATPA and GAD65A in bipolar disorder was associated with neither rapid cycling nor the use of lithium Interestingly the presence of GAD65A (and not that of TPOA and ATPA) tended to be associated with the activity of bipolar disorder The level of TPOA was negatively correlated with the serum level of sIL-2R a measure of T cell activation

Conclusion Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO HK ATPase

and GAD65