Introdução: O Transtorno Obsessivo-Compulsivo (TOC) é reconhecido como um transtorno heterogêneo. Esta heterogeneidade dificulta a interpretação dos resultados dos estudos. A descrição de grupos de pacientes mais homogêneos pode facilitar a identificação desta busca, já que pode identificar fenótipos que sejam hereditários e válidos do ponto de vista genético. A abordagem categorial e dimensional são estratégias reconhecidas para a identificação de subgrupos mais homogêneos de pacientes. Dentro da abordagem categorial, o subgrupo de pacientes com início precoce dos sintomas obsessivo-compulsivo (SOC), e o subgrupo de TOC associado a transtorno de tiques apresentam características clínicas semelhantes, com evidências de sobreposição destas características entre os dois grupos. Os objetivos deste estudo foram: investigar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) e TOC de início tardio (GT); e pesquisar características demográficas e clínicas dos pacientes com TOC de início precoce (GP) com tiques e pacientes com TOC de início precoce (GP) sem tiques. Metodologia: Trezentos e trinta pacientes com diagnóstico de TOC de acordo com o DSM-IV foram avaliados diretamente com os seguintes instrumentos: Entrevista Clínica Estruturada para o DSM-IV - Transtornos do Eixo I; Escala Yale-Brown de Sintomas Obsessivo-Compulsivos - Y-BOCS; Escala Dimensional para Avaliação de Presença e Gravidade de Sintomas Obsessivo-Compulsivos DY-BOCS; Escala de Avaliação Global de Tiques desenvolvida pelo Yale Child Study Center - YGTSS. Foi considerado TOC de início precoce se os sintomas dos pacientes tiveram início até os 10 anos de idade (160 pacientes). Os pacientes com início de sintomas entre 11 e 17 anos (95 pacientes) foram denominados grupo intermediário, enquanto aqueles após os 17 anos foram chamados grupo de início tardio (75 pacientes). Resultados: os pacientes do GP se diferenciaram dos pacientes do GT por apresentar maior freqüência do sexo masculino; maior freqüência de história familiar de SOC em familiares de primeiro grau; maiores escores da escala Y-BOCS para compulsões e Y-BOCS total; maior chance de ter obsessões de contaminação; maior chance de ter compulsões de repetição, colecionismo, diversas e compulsões do tipo tic-like; menor chance de ter compulsões de contagem; maior chance de apresentar sintomas da dimensão de \"colecionismo\"; maior gravidade nas dimensões de \"agressão/violência\", \"diversas\" e escore global da escala DY-BOCS; maior número médio de comorbidades; maior probabilidade de ocorrência de transtorno de ansiedade de separação, fobia social, transtorno dismórfico corporal e transtorno de tiques; menor chance de apresentar transtorno de estress pós-traumático; e maior chance de ter redução de 35% dos sintomas na escala Y-BOCS. O GP com tiques se diferenciou do GP sem tiques por apresentar maior prevalência de fenômenos sensoriais; menor chance e menor gravidade de ter a dimensão de \"contaminação/limpeza\" e menor gravidade no escore global da escala DY-BOCS; menor chance de apresentar transtorno de humor, transtorno unipolar, transtornos ansiosos, fobia social e skin picking, e maior a chance de apresentar diminuição de 35% dos sintomas na escala Y-BOCS. Os resultados sugeriram que as diferenças encontradas entre os grupos precoce, intermediário e tardio foram devidas à própria idade de início, e outras diferenças foram devidas à presença de tiques. / Introduction: Obsessive-compulsive disorder (OCD) is recognized as a heterogeneous condition. This heterogeneity obscures the interpretation of the results of the studies. The description of more homogeneous groups of patients can facilitate the identification of this search, since it can identify phenotypes that are hereditary and valid to the genetic point of view. Categorical and dimensional approaches are recognized strategies for the identification of more homogeneous subgroups of patients. Regarding the categorical approach, the subgroup of patients with early age at onset of the obsessive-compulsive symptoms (OCS), and the tic-related-OCD subgroup present similar clinical characteristics, with evidences of an overlap of these characteristics between the two groups. The aims of this study were: to investigate clinical and demographic characteristics of the early age at onset subgroup (EO), compared to the late onset subgroup (LO); and to investigate demographic and clinical characteristics of early age at onset OCD patients, with and without comorbid tic disorders. Methodology: Three hundred and thirty patients with the diagnosis of OCD according to the DSM-IV were directly assessed with the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition - SCID-I/P; Yale-Brown Obsessive-Compulsive Scale - Y-BOCS; Dimensional Yale-Brown Obsessive-Compulsive Scale - DY-BOCS and Yale Global Tics Severity Scale - YGTSS. We considered early age at onset when OCS began before the age of 10 (160 patients). Patients with age at onset between 11 and 17 years old were termed intermediate group (95 patients), whereas those with age at onset after 17 years old were designated as late onset OCD (75 patients). Results: EO patients differed from LO patients in terms of presenting higher frequency of the male gender; higher frequency of a family history of OCS; higher Y-BOCS for compulsions and total Y-BOCS scores; higher chance of presenting contamination obsessions, repeating, hoarding, miscellaneous and tic-like compulsions; lower chance of having counting compulsions; higher probability of presenting symptoms of \"hoarding\" dimension; higher severity in \"aggression/violence\" and \"miscellaneous\" dimensions and global DY-BOCS scale score; higher mean number of comorbidities; higher probability of presenting separation anxiety disorder, social phobia, body dysmorphic disorder and tic disorders; lower chance of presenting posttraumatic stress disorder; and a higher chance of having a 35% reduction on the Y-BOCS scale. The EO subgroup with tic disorders differed from the EO without tics for presenting higher chance of having sensory phenomena, somatic obsessions; lower chance and lower score in the DY-BOCS scale; lower chance of presenting mood disorder, depressive disorder, anxiety disorders, social phobia and skin picking; higher chance of having a 35% reduction on the Y-BOCS scale. Results suggested that the differences found among early, intermediated and late onset groups with early onset were secondary to the own age at onset, and other differences were secondary to the presence of tics.

Até o momento, são escassos os estudos que se propuseram a investigar o funcionamento cognitivo das crianças e adolescentes com Transtorno Obsessivo-Compulsivo (TOC). Os estudos disponíveis apontam que essa população apresenta pior desempenho nos testes neuropsicológicos que avaliam as funções executivas, a memória não-verbal, o funcionamento visuoespacial e a velocidade de processamento, em comparação aos sujeitos saudáveis. Mesmo com esses achados, poucos autores averiguaram a influência dos tratamentos de primeira linha para o TOC [Terapia Cognitivo- Comportamental (TCC) e inibidores de recaptura de serotonina (IRS)] na cognição. Vale ressaltar que tais estudos expressam resultados divergentes, não havendo um consenso sobre a melhora ou manutenção dos déficits no desempenho dos jovens após o tratamento. Diante deste contexto, o presente estudo teve como objetivos: A) Comparar as características sociodemográficas e clínicas e o funcionamento cognitivo de uma amostra pediátrica com TOC e sujeitos saudáveis; B) Verificar as modificações no funcionamento cognitivo do grupo TOC após 14 semanas de tratamento farmacológico ou psicoterápico. Para isso, foram avaliados 82 crianças e adolescentes com TOC e 82 controles saudáveis, com idades entre 6-17 anos, com questionários para avaliação de sintomas psiquiátricos e uma bateria de testes neuropsicológicos. Todos os participantes do estudo foram submetidos às avaliações na linha de base. Os pacientes, após randomização para TCC em grupo ou fluoxetina (FLX), foram reavaliados findadas 14 semanas de tratamento. A análise dos dados indicou que os pacientes apresentam desempenho cognitivo global pior que os controles, havendo diferenças significativas no QI de execução, nas habilidades visuoconstrutivas, na memória episódica não verbal e na flexibilidade mental. Variáveis clínicas, como idade de início dos sintomas, gravidade dos sintomas do TOC, dimensões dos sintomas obsessivo-compulsivos e comorbidades, não correlacionaram com o pior desempenho dos pacientes nos diferentes testes neuropsicológicos. Após 14 semanas de tratamento, embora os pacientes tenham apresentado melhora clínica dos sintomas obsessivo-compulsivos, o mesmo não ocorreu com as diferentes funções neuropsicológicas, mesmo naquelas que estavam prejudicadas na linha de base. De acordo com os resultados do presente estudo, as crianças e adolescentes com TOC apresentam pior desempenho cognitivo global em provas neuropsicológicas quando comparados aos controles saudáveis. O fato da melhora dos sintomas não ser acompanhada da melhora do desempenho neuropsicológico dos pacientes, sugere que as alterações cognitivas observadas no grupo TOC sejam relacionadas à própria neurobiologia do transtorno, independentemente da gravidade dos sintomas. Futuros estudos longitudinais serão necessários para aumentar a compreensão do funcionamento cognitivo dos jovens com TOC e as implicações do tratamento na sua cognição no longo prazo / To date, only a few studies have investigated the cognitive functioning of children and adolescents with Obsessive-Compulsive Disorder (OCD). These studies indicate that youth with OCD present a worse performance in neurocognitive tests that assess the executive functions, nonverbal memory, visuospatial functioning and processing speed. Despite these findings, only a few authors have investigated the influence of Cognitive-Behavioral Therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) on the cognition of youth with OCD. It is worth noting that these studies express divergent results, and there is no consensus on the improvement or maintenance of the cognitive deficits after treatment. In this context, the present study aimed: A) To compare the sociodemographic/ clinical characteristics and the cognitive functioning of youth with OCD and healthy controls; B) To verify the changes in cognitive functioning of children and adolescents with OCD after 14 weeks of randomized pharmacological or cognitive-behavioral treatment. Eighty-two children and adolescents with OCD and 82 healthy controls, aged between 6 and 17 years, were evaluated by means of structured questionnaires and a battery of neuropsychological tests. All participants underwent assessments at baseline. The OCD group, after being randomized to group CBT or Fluoxetine (FLX), was re-evaluated after 14 weeks of treatment. Data analyses indicated that patients presented a worse cognitive performance when compared to the healthy controls, with significant differences in performance IQ, visuoconstructive skills, nonverbal memory, and mental flexibility. Clinical variables, such as age of onset, severity of OCD symptoms, OCD dimensions and comorbidities, did not correlate with poorer performance on neuropsychological tests. Although patients had clinical improvement after 14 weeks of treatment, the same did not occur with the cognitive performance, even in those functions which were impaired at baseline. According to the results of the present study, youth with OCD present a worse cognitive performance when compared to controls. The fact that the improvement of the symptoms is not followed by the improvement of the neuropsychological performance suggests that the cognitive deficits observed in the OCD group may be related to the neurobiology of the disorder, regardless of the symptom severity. Future longitudinal studies will be needed to further clarify the cognitive functioning of youth with OCD and the implications of treatment on their cognition in the long run

Das Gefühl die eigenen Handlungen selbst zu verursachen und deren Konsequenzen zu kontrollieren, ist ein wesentlicher Bestandteil unserer Selbstwahrnehmung und wird als Erleben von Urheberschaft oder Autorenschaft bezeichnet. Die zugrunde liegenden neurokognitiven Mechanismen sind bislang nur unzureichend verstanden. In zwei Experimenten zur Handlungswahrnehmung wurde bei gesunden Probanden mittels Elektroenzephalogramm (EEG) die Hirnaktivität auf visuelles Handlungsfeedback erfasst. Reduzierte neuronale Aktivität (sensorische Attenuierung) auf selbst versus extern generiertes Feedback wurde als implizites Maß für das Erleben von Urheberschaft verwendet. Die Ergebnisse zeigten, dass das Ausmaß der neuronalen Attenuierung stärker von der Präsenz einer Handlung sowie vorausgehenden Hinweisreizen abhing, als von präzisen Vorhersagen durch spezifische Kontingenzregeln. Die explizite Beurteilung der eigenen Urheberschaft dagegen beruhte primär auf hoher Kontingenz von Handlung und Feedback, während externe Hinweisreize nur in Kontexten herangezogen wurden, in denen Kontingenzinformationen nicht ausreichten. Eine dritte EEG Studie untersuchte Patienten mit Zwangsstörung, welche durch abweichendes Erleben der Vollendung und Urheberschaft für Handlungsergebnisse gekennzeichnet ist. Die Ergebnisse zeigten eine fehlende neuronale Attenuierung selbst generierter Handlungskonsequenzen bei Zwangspatienten. Verkörperte Signale wurden dabei weniger stark genutzt für Vorhersagen des Handlungsfeedbacks. Zusammenfassend trägt die vorliegende Arbeit zur Validierung der sensorischen Attenuierung als implizites Maß des Erlebens von Urheberschaft bei. Die Ergebnisse zeigen, dass das Erleben von Urheberschaft auf einer Integration multipler verkörperter und externer, kontextueller Hinweisreize beruht. Dieser Integrationsmechanismus scheint bei Zwangspatienten gestört zu sein und führt möglicherweise zu dem mangelnden Gefühl von Handlungsabschluss und Urheberschaft. / The experience of causing and controlling one s own actions and their consequences is a major aspect of our self-awareness, which has been termed sense of agency or experience of authorship. The underlying neural and cognitive mechanisms are still not well understood. In two consecutive experiments on action awareness, the electroencephalogram (EEG) of healthy participants was recorded to measure brain activity related to the perception of visual feedback. Reduced neuronal activity (sensory attenuation) in response to self- versus externally generated feedback was taken as an implicit measure for the sense of agency. The results showed that the amount of sensory attenuation was primarily determined by the mere presence of an action and external cues independent of highly precise predictions based on specific contingency rules. Explicit judgments of agency, in contrast, were mainly determined by high degrees of contingency between action and feedback, and external cues had an influence only in ambiguous contexts where contingency information was not reliable enough. A third EEG study investigated patients suffering from obsessive-compulsive disorder (OCD). OCD is characterized by lacking a sense of completion and agency for action outcomes. The results of this study revealed that OCD patients fail to suppress the consequences of their own action. Embodied signals were used less by patients for making specific predictions of the action feedback. In conclusion, the present work offers validation of sensory attenuation as an implicit measure of non-conceptual agency experience, and provides evidence that the sense of agency is based on an optimal integration of multiple embodied and external, contextual cues. Moreover, the present research reveals for the first time, to our knowledge - reduced gating of extracorporeal sensory action consequences in patients suffering from OCD, which may explain aberrant feelings of action completion and agency in these patients.

O transtorno obsessivo-compulsivo (TOC) é uma condição clínica crônica e associada a prejuízo funcional. Esse transtorno é caracterizado pela ocorrência de obsessões e/ou compulsões. Alguns fatores ambientais relacionados ao TOC são as experiências adversas na infância e adolescência (EAIA), as quais podem ter efeitos no desenvolvimento cognitivo, socioemocional e comportamental. Além disso, há outros processos envolvidos como a resiliência, a esquiva experiencial e as experiências dissociativas, que podem ser potenciais mediadores. Apesar de ser reconhecida essa importância, há poucos estudos que tenham investigado conjuntamente as EAIA e esses processos em pacientes com TOC, irmãos discordantes para TOC e controles. Diante disso, o presente estudo teve como objetivos: 1a) comparar os três grupos quanto a EAIA, resiliência, esquiva experiencial, experiências dissociativas e investigar se essas variáveis são preditoras de qual grupo o participante pertence; 1b) caracterizar e comparar a trajetória das EAIA nos três grupos. 2a) verificar se EAIA, esquiva experiencial, resiliência e experiências dissociativas predizem desfechos clínicos (número de transtornos psiquiátricos, gravidade de sintomas obsessivo-compulsivos, depressivos e ansiosos); 2b) verificar se a relação entre EAIA e sintomas obsessivo-compulsivos, de ansiedade e depressão é mediada por processos de esquiva experiencial, resiliência e experiências dissociativas. A amostra foi composta por 72 participantes divididos em 24 trios (paciente, irmão sem TOC e controle). Do ponto de vista estatístico, para a comparação entre os grupos foram feitos testes de Kruskal-Wallis/Wilcoxon, modelos de regressão multinomiais e modelos de equações de estimação generalizadas. Para os desfechos de relação entre as variáveis foram feitos modelos de regressão de Poisson e lineares e modelos de mediação. Os instrumentos utilizados foram: escala de cronologia de exposição ao abuso e aos maustratos; escala de resiliência para adultos; questionário de aceitação e ação II; questionário multidimensional de esquiva experiencial; e escala de experiências dissociativas; além dos dados clínicos. Em relação às EAIA, observou-se maior frequência de abuso emocional entre pares no grupo de pacientes comparados a controles. Os pacientes tiveram menores escores de resiliência e maiores de esquiva experiencial que os demais grupos. No entanto, os irmãos não se diferenciaram dos controles. A esquiva experiencial foi a melhor variável para diferenciar tanto os grupos pacientes de não pacientes quanto irmãos de controles. As variáveis preditoras de desfechos clínicos foram as experiências dissociativas e as EAIA na amostra de pacientes. Parte da relação entre as EAIA (e dentre esses destacou-se o abuso emocional entre pares) e os sintomas depressivos foi mediada pela resiliência e pela esquiva experiencial. Os achados do presente estudo destacaram a importância da mensuração dos EAIA, sobretudo de escalas que contemplem o abuso emocional entre pares. Destacou-se a importância do estudo de processos como a resiliência, a esquiva experiencial e as experiências dissociativas como variáveis preditoras e mediadoras de desfechos psicopatológicos. Espera-se que os dados do presente estudo motivem estudos futuros que tratem da importância da prevenção dos EAIA e do desenvolvimento de habilidades sociais e fatores de proteção relacionados à resiliência e seu impacto no desenvolvimento / Obsessive-compulsive disorder (OCD) is a chronic clinical condition and associated with functional impairment. This disorder is characterized by the occurrence of obsessions and/or compulsions. Some environmental factors related to OCD are adverse experiences in childhood and adolescence (AECA), which may have effects on cognitive, behavioral and emotional development. In addition, there are other processes involved such as resilience, experiential avoidance, and dissociative experiences, which may be potential mediators. Although this importance is recognized, there are few studies that have investigated jointly the AECA and these processes in patients with OCD, siblings without OCD and controls. The objective of this study was 1a) to compare the three groups with regard to AECA, resilience, experiential avoidance, dissociative experiences, and to investigate whether these variables are predictors of which group belongs to 1b) to characterize and compare the trajectory of AECA in all three groups. 2a) to verify if AECA, experiential avoidance, resilience and dissociative experiences predict clinical outcomes (number of psychiatric disorders, severity of obsessive-compulsive, depressive and anxious symptoms); 2b) to verify if the relationship between AECA and obsessivecompulsive symptoms, of anxiety and depression is mediated by processes of experiential avoidance, resilience and dissociative experiences. The sample consisted of 72 participants divided into 24 trios (patient, sibling without OCD and control). The statistical analyzes used were Kruskal-Wallis/Wilcoxon tests, multinomial regression models and generalized estimation equation models to compare the groups. Poisson and linear regression models and mediation models were used for the relationship outcomes between the variables. The instruments used were: maltreatment and abuse chronology of exposure; resilience scale for adults; acceptance and action questionnaire II; multidimensional experiential avoidance questionnaire; dissociative experiences scale; in addition to clinical data. In relation to AECA, a higher frequency of peer emotional abuse was observed in the group of patients compared to controls. Patients had lower resilience scores and higher experiential avoidance than the other groups. However, the siblings did not differ from controls. Experiential avoidance was the best variable to differentiate both patient and non-patient groups and siblings from controls. Predictors of clinical outcomes were dissociative and AECA in the patient sample. Part of the relationship between AECA (among which was peer emotional abuse) and depressive symptoms was mediated by resilience and experiential avoidance. The findings of the present study emphasized the importance of measuring AECA, especially, scales that contemplate emotional abuse between peers. The importance of the study of processes such as resilience, experiential avoidance and dissociative experiences as predictors and mediators of psychopathological outcomes was highlighted. The data from the present study are expected to motivate future studies that address the importance of AECA prevention and the development of social skills and protection factors related to resilience and its developmental impact

Trotz zahlreicher Untersuchungen lässt sich bei der Zwangsstörung noch kein einheitliches, alle Befunde integrierendes Krankheitsmodell formulieren. Die Verarbeitung von emotionalen Reizen könnte bei Personen mit Zwangsstörungen verändert sein. Dies trägt möglicherweise zur Entwicklung und Aufrechterhaltung der Störung bei. Das Ziel der vorliegenden Arbeit war es, spezifische Komponenten dieser Verarbeitung zu untersuchen. Zuerst wurde in zwei unterschiedlichen Studien überprüft, ob die Orientierung der Aufmerksamkeit zu neuen Reizen bei Patienten mit Zwangsstörungen verstärkt ist. Zu diesem Zweck wurden durch neue Reize evozierte Potentiale im Elektroenzephalogramms (EEG) gemessen. Anschließend wurde in einer Studie überprüft, ob das Verhältnis der Aktivierungen von dem Vermeidungs- zum Annäherungssystem bei den Betroffenen verändert ist. Dies lässt sich an Hand der Ermittlung der hemisphärischen Verteilung von Alpha-Wellen in frontalen Hirnregionen feststellen. Die Ergebnisse der ersten beiden Studien ergaben, dass Patienten unabhängig vom emotionalen Kontext eine stärkere Aufmerksamkeitshinwendung zu neuen Reizen zeigen (Studie 1), was allerdings nicht beobachtet wurde, wenn die neuen Reize innerhalb des Aufmerksamkeitsfokus lagen (Studie 2). Dieses Ergebnis wurde als überaktives Gefahrenerkennungssystem bei Patienten interpretiert. Weiterhin ließ sich feststellen, dass Patienten im Vergleich zu gesunden Kontrollen in frontalen Hirnregionen eine Verlagerung der Alpha Asymmetrie zur linken Gehirnhemisphäre aufwiesen (Studie 3). Dieser Befund wurde unabhängig von einer Stimulierung durch emotionale Reize gemacht. Er lässt sich als stärkere Aktivierung des Vermeidungs- im Verhältnis zum Annäherungssystem deuten. Zusammengefasst zeigte sich bei Patienten mit Zwangsstörungen eine veränderte Verarbeitung von emotionalen Reizen. Aus diesen Befunden können spezifische Empfehlungen für die Behandlung der Störung abgeleitet werden. / It is so not possible to formulate a disease model of obsessive-compulsive disorder (OCD) that integrates all the results of the many studies carried out. The neural processing of emotional stimuli might be altered in people with OCD. This might play an important role in the development and maintenance of OCD. The present work aimed to investigate specific components of the neural processing of emotional stimuli. The first two studies examined if the orienting of attention towards novel stimuli is enhanced in patients with OCD. For this purpose the event-related brain potentials evocated by novel stimuli in the electroencephalogram were recorded. The third study tested if the relationship between the withdrawal-avoidance mode and the approach mode of the motivational brain system is altered in OCD patients. This can be assessed by the hemispheric distribution of alpha power in frontal brain regions. The results of the first two studies showed that the orienting of attention towards novel stimuli is enhanced in patients with OCD independently of the emotional context condition (study 1), which could not be observed if the novel stimuli were listened to in active attentional mode (study 2). This was interpreted as a hypersensitive threat detection system. Further, it was found that patients showed a shift of frontal alpha activity to the left hemisphere compared to healthy control subjects (study 3). This result was independent of the viewing of emotional stimuli. It can be concluded that the avoidance mode is relatively increased in patients with OCD. Taken together, patients showed an altered neural processing of emotional stimuli. Specific recommendations for he treatment of the disorder can be drawn out of them.

Patienten mit Zwangserkrankung (OCD) weisen selektive Defizite in der Verarbeitung komplexer visueller Informationen sowie im Bereich der Exekutivfunktionen auf, welche sich teilweise auch bei depressiv erkrankten Patienten finden. Das Ziel der Untersuchung bestand darin, kognitive Defizite bei OCD-Patienten zu identifizieren, die ein spezifisches Korrelat der Zwangssymptomatik in Abgrenzung zu Patienten mit unipolarer Depression (MD) darstellen. Vierzig OCD-Patienten, 20 MD-Patienten sowie 40 gesunde Kontrollprobanden wurden hinsichtlich sieben kognitiver Domänen neuropsychologisch untersucht. Innerhalb der OCD-Stichprobe wurden die Leistungen von hoch- und niedrigdepressiven OCD-Patienten nach BDI-Mediansplit (MedianBDI = 15,5) sowie von Patienten mit vs. ohne familiäre Häufung der Erkrankung einander gegenübergestellt. Die OCD-Patienten zeigten Beeinträchtigungen gegenüber Gesunden in allen untersuchten Bereichen bis auf die Domäne „Verbales Gedächtnis“. Die Defizite in den Domänen „Visuelle Organisation“ und „Problemlösen/Arbeitsgedächtnis“ erwiesen sich spezifische Korrelate der Zwangssymptomatik. Die MD-Patienten wiesen ein mit den OCD-Patienten überlappendes Defizit in der Domäne „Verbale Flüssigkeit“ auf. In der OCD-Gruppe korrelierte die Schwere der Zwangsgedanken negativ mit der Domäne „Visuelle Organisation“. Das Ersterkrankungsalter korrelierte negativ mit der Domäne „Visuomotorik/Aufmerksamkeitswechsel“. Es bestand kein bedeutsamer Einfluss der depressiven Begleitsymptomatik sowie der familiären Häufung von OCD auf die kognitiven Leistungen. Anhand dieser Arbeit wurde belegt, dass es sich bei den Defiziten der OCD-Patienten hinsichtlich der visuellen Gestalterfassung sowie der mentalen Manipulation komplexer visueller Information um spezifische Merkmale der Zwangserkrankung in Abgrenzung zu milden Formen unipolarer Depression handelt. Eine leichte depressive Begleitsymptomatik mindert die kognitiven Leistungen von OCD-Patienten nicht zusätzlich. / Patients suffering from Obsessive Compulsive Disorder (OCD) show selective deficits both in the processing of complex visual information and regarding executive functions. Patients with Major Depression (MD) were found to have, in parts, similar impairments. The aim of the present study was to identify those cognitive deficits in OCD patients which are a correlate specific to OCD, as opposed to MD patients. We also looked at the influence of the following factors on the cognitive functions of OCD patients: concomitant depression, severity of the disorder, age at onset, and the occurrence of OCD symptoms among immediate family. Forty OCD patients, 20 MD patients, and 40 healthy controls underwent neuropsychological assessment and were compared across seven cognitive domains. For the OCD sample, results of highly and slightly depressive OCD patients, according to BDI median split (medianBDI = 15.5) were compared, as were those of patients with and without a family history of the disorder. OCD patients showed impairments across all domains, not including “Verbal Memory”. The deficits in the domains “Visual Organisation” and “Problem Solving/Working Memory” were found to be specific correlates of obsessive-compulsive symptoms. MD patients had a deficit in “Verbal Fluency” similar to that of OCD patients. Within the OCD group, we found a negative correlation between the current severity of obsessive thoughts and the domain “Visual Organisation”. Age at onset correlated negatively with “Visual Motor Speed/Attentional Set-Shifting”. Neither concomitant depression nor a family history of OCD symptoms influenced cognitive performance significantly. The study proved that the deficits of OCD patients concerning visual organisation and mental manipulation of complex, visually coded information are features specific to this disorder, in delimitation from mild forms of major depression. Concomitant mild forms of depression do not further impair cognitive functions in OCD-patients.

Les Troubles Obsessionnels et Compulsifs (TOC) sont un trouble mental sévère et fréquemment résistant. La physiopathologie du trouble se caractérise par des anomalies au sein des boucle cortico-striato-thalamo-cortical entrainant une hyper-activité du cortex orbito-frontal, du cortex cingulaire antérieur, du putamen. Au cours des dernières années, des anomalies structurales et fonctionnelles du cervelet ont de plus été mise en évidence dans les TOC venant compléter le modèle existant.Nous avons mise au point un protocole de traitement par tDCS ciblant le cortex orbito-frontal gauche et le cervelet droit pour les TOC résistants. Dans une première étude, nous avons étudié la faisabilité de ce protocole de traitement dans une étude ouverte. Cette étude a mis en évidence une réduction significative des symptômes dans une population de patient à haut niveau de résistance. Dans une deuxième étude, nous avons évaluer l’effet de ce traitement dans un protocole randomisé, contrôlé et parallèle contre placebo. Cette étude n’a pas confirmé l’efficacité de ce protocole de traitement. Dans cette même population, nous avons au cours du protocole mesuré les paramètres d’excitabilité corticale au niveau du cortex moteur par stimulation magnétique transrânienne. Nous avons ainsi mis en évidence que la tDCS provoquait une augmentation significative des processus d’inhibition (Short Interval Cortical Inhibition : SICI ) et une diminution non significative des processus de facilitation (Intra Cortical Facilitation : ICF). L’étude des effets cliniques et électro-physiologiques de cette approche thérapeutique novatrice dans les TOC résistants n’a pas permis de confirmer son intérêt clinique malgré un impact de ce protocole sur les modifications de l’excitabilité corticale inhérentes aux troubles. Ces données ont été mise en relation avec la littérature afin de proposer des perspectives d’évolution dans l’utilisation de la tDCS dans les TOC résistants / Obsessive-compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Neurobiological models of OCD are based on an imbalance between the direct (excitatory) and indirect (inhibitory) pathway within this cortico-striato-thalamo-cortical loops, which causes hyperactivation in the orbito-frontal cortex, the cingular anterior cortex, the putamen. More recently, the role of cerebellum in the OCD physiopathology has been brought to light by studies showing structural and functional abnormalities. We proposed to use tDCS as a therapeutic tool for resistant OCD by targeting the hyperactive left orbito-frontal cortex with cathodal tDCS (assumed to decrease cortical excitability) coupled with anodal cerebellar tDCS. In a first study, we studied the feasibility of this treatment protocol in an open-trial. This study found a significant reduction in symptoms in a population with a high level of resistance. In a second study, we evaluated the effect of this treatment in a randomized-controlled trial. This study did not confirm the effectiveness of this intervention. We have assessed motor cortex cortical excitability parameters by transcranial magnetic stimulation. We thus demonstrated that the tDCS caused a significant increase of inhibition processes (Short Interval Cortical Inhibition: SICI) and a nonsignificant decrease in the facilitation processes (Intra Cortical Facilitation (ICF)). In addition, clinical improvement assessed by Clinical Global Impression at the end of the follow-up period (3 months) was positively correlated with SICI at baseline.tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum decreased hyper-excitability in the motor cortex but was not significantly effective in SSRI- resistant OCD patients. These works were discussed in light of the available literature to create future prospect in the field of tDCS treatment for OCD resistant patients

A execução de movimentos voluntários é precedida por processos preparatórios que manifestam-se eletrofisiologicamente como um potencial elétrico lento denominado Bereitschaftspotential. As investigações sobre o significado fisiológico desses potenciais mostram-se muitas vezes inconclusivas devido à dificuldade de isolamento dos fatores ambientais e endógenos que os influenciam. Dentre essas variáveis, a expressão consciente do ato motor tem sido negligenciada por grande parte dos pesquisadores. O presente trabalho consiste em uma série de estudos eletrofisiológicos que visam demonstrar a influência do controle consciente sobre os processos preparatórios motores. Parte-se do desenvolvimento de protocolos comportamentais que modulam o envolvimento consciente sobre processos motores. Desse modo, verificamos que grande parte do Bereitschaftspotential comumente observado durante a geração de movimentos espontâneos estão associados com a escolha deliberada de agir. Em seguida, são investigadas como a variável em questão pode afetar os processos relacionados com a livre escolha de movimentos. Nossos resultados indicam que processos relacionados ao controle consciente afetam nitidamente a expressão de livre escolha sobre os potenciais preparatórios motores. Por fim, nós demonstramos como a influência do controle consciente nos processos motores pode estar afetada em pacientes com transtorno obsessivo-compulsivo / The execution of voluntary movements is preceded by preparatory processes that electrophysiologically are manifested as a slow electric potential called Bereitschaftspotential. Investigations on the physiological significance of these potentials are often inconclusive due to the difficulty of isolating the environmental or endogenous factors that influence them. Among these factors, the conscious expression of the motor act has been neglected by most researchers. The present work consists of a series of electrophysiological studies aimed at demonstrating the influence of conscious control on preparatory motor processes. Firstly, behavioral protocols that modulate the conscious involvement in motor control are proposed. Using these methods, we found that great part of the Bereitschaftspotential commonly observed during the generation of spontaneous movements is associated with the deliberate choice to act. Next, we investigated how this factor variable affects the processes related to the free mode of movement selection. Our results indicate that processes related to conscious control clearly affect the manifestations of free choice in preparatory motor potentials. Finally, we here demonstrated how the influence of conscious control on the motor processes can be affected in the obsessive-compulsive disorder

INTRODUÇÃO: Testes provocativos com drogas serotonérgicas não apresentaram resultados consensuais em pacientes com TOC, sugerindo que a atividade serotonérgica seja heterogênea neste transtorno. É possível que a disfunção serotonérgica se relacione à resistência ao tratamento com inibidores de recaptura de serotonina (IRS) neste transtorno. O objetivo deste estudo foi comparar a atividade serotonérgica em pacientes com TOC resistente e responsivo ao tratamento com IRS e voluntários normais através de teste provocativo com citalopram. MÉTODOS: Foram estudados 30 pacientes com TOC resistente a IRS (RT), 30 pacientes com TOC respondedor (RP) e 30 voluntários sem transtorno mental (CN) pareados por sexo e idade. Cada indivíduo recebeu 20 mg de citalopram intravenoso. Foram dosados: prolactina, cortisol, hormônio de crescimento no plasma e serotonina em plasma rico em plaquetas nos seguintes tempos: -20, 0, 20, 40, 60, 80, 100, 120, 140 e 160 minutos. Como medidas da variação hormonal foram comparadas a variação percentual máxima (delta%) e a área sob a curva da variação. RESULTADOS: O citalopram não induziu sintomas ansiosos ou piora dos sintomas obsessivo-compulsivos nos pacientes. Também não houve mudanças significativas na concentração periférica de serotonina e na concentração de GH. A droga induziu um pico de secreção de prolactina no grupo controle (delta%=65,76 ± 105,1) maior que nos grupos RT e RP (RT delta%=17,41 ± 31,06; RP delta%=15,87 ± 31,71; p<0,05 em relação ao grupo controle). A secreção de cortisol mostrou-se atenuada apenas no grupo RT: (RT delta%=20,98 ± 58,14; RP delta%= 47,69 ± 66,94; CN delta%= 63,58 ± 88,4; p<0,05). CONCLUSÕES: Tanto pacientes resistentes como respondedores ao tratamento com IRS apresentaram resposta atenuada de prolactina ao citalopram em comparação a voluntários saudáveis, mas apenas pacientes resistentes apresentaram também resposta atenuada de cortisol, sugerindo maior disfunção serotonérgica neste grupo. / INTRODUCTION: Serotonergic pharmacological challenge tests have failed to produce consensual results in patients with OCD diagnosis, suggesting a heterogeneous 5-HT activity in this disorder. It is possible that serotonergic dysfunction is related with inadequate response to treatment with serotonin reuptake inhibitors (SRI). The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in serotonin reuptake inhibitors treatment resistant and responders OCD patients and healthy volunteers. Methods: Thirty OCD resistant patients, 30 responders patients and 30 healthy volunteers, age and sex matched, were included. Each subject received 20 mg of intravenous citalopram. Prolactin, cortisol, growth hormone and serotonin were determined at the following times after the onset of citalopram infusion: -20, 0, 20, 40, 60, 80, 100, 120, 140 and 160 minutes. The maximal percentage variation (delta%) and area under the curve were compared as measures of hormonal variation. RESULTS: Citalopram has not induced any worsening of anxious or obsessive-compulsive symptoms among patients. No significant changes were observed either at platelet rich plasma serotonin concentration or at plasma growth hormone concentration. Citalopram has induced an increase in prolactin secretion in the control group (delta%=65.76 ± 105.1) while RT and RP groups showed blunted prolactin response (RT delta%=17.41 ± 31.06; RP delta%=15.87 ± 31.71; p<0.05). The cortisol response to citalopram was attenuated only in the RT group: (RT delta%=20.98 ± 58.14; RP delta%= 47.69 ± 66.94; CN delta%= 63.58 ±88.4; p<0.05). CONCLUSIONS: We concluded that either treatment resistant as responders patients have blunted prolactin response to citalopram, but only resistant patients also show an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group.

A execução de movimentos voluntários é precedida por processos preparatórios que manifestam-se eletrofisiologicamente como um potencial elétrico lento denominado Bereitschaftspotential. As investigações sobre o significado fisiológico desses potenciais mostram-se muitas vezes inconclusivas devido à dificuldade de isolamento dos fatores ambientais e endógenos que os influenciam. Dentre essas variáveis, a expressão consciente do ato motor tem sido negligenciada por grande parte dos pesquisadores. O presente trabalho consiste em uma série de estudos eletrofisiológicos que visam demonstrar a influência do controle consciente sobre os processos preparatórios motores. Parte-se do desenvolvimento de protocolos comportamentais que modulam o envolvimento consciente sobre processos motores. Desse modo, verificamos que grande parte do Bereitschaftspotential comumente observado durante a geração de movimentos espontâneos estão associados com a escolha deliberada de agir. Em seguida, são investigadas como a variável em questão pode afetar os processos relacionados com a livre escolha de movimentos. Nossos resultados indicam que processos relacionados ao controle consciente afetam nitidamente a expressão de livre escolha sobre os potenciais preparatórios motores. Por fim, nós demonstramos como a influência do controle consciente nos processos motores pode estar afetada em pacientes com transtorno obsessivo-compulsivo / The execution of voluntary movements is preceded by preparatory processes that electrophysiologically are manifested as a slow electric potential called Bereitschaftspotential. Investigations on the physiological significance of these potentials are often inconclusive due to the difficulty of isolating the environmental or endogenous factors that influence them. Among these factors, the conscious expression of the motor act has been neglected by most researchers. The present work consists of a series of electrophysiological studies aimed at demonstrating the influence of conscious control on preparatory motor processes. Firstly, behavioral protocols that modulate the conscious involvement in motor control are proposed. Using these methods, we found that great part of the Bereitschaftspotential commonly observed during the generation of spontaneous movements is associated with the deliberate choice to act. Next, we investigated how this factor variable affects the processes related to the free mode of movement selection. Our results indicate that processes related to conscious control clearly affect the manifestations of free choice in preparatory motor potentials. Finally, we here demonstrated how the influence of conscious control on the motor processes can be affected in the obsessive-compulsive disorder