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

Modelos experimentais do transtorno obsessivo compulsivo (TOC) com humanos mostram que uma forma de evocar comportamentos de checagem é apresentar instruções que especificam consequências aversivas para o comportamento inefetivo na execução de tarefas. Atualmente há na área somente um estudo experimental com delineamento de sujeito único. Os presentes dois experimentos com 16 participantes verbalmente habilidosos tiveram o objetivo de testar se instruções com especificação de consequência aversiva ou apetitiva poderiam ter o efeito de produzir respostas de checagem. Em um restaurante experimental, as instruções foram apresentadas durante uma tarefa de separação de sementes misturadas. No Experimento 1, cinco de oito participantes apresentaram maiores porcentagens de checagens sob especificação de consequência aversiva. No Experimento 2, sete de oito participantes apresentaram maiores porcentagens sob especificação de consequência apetitiva. Concluiu-se que determinadas instruções alteraram a função discriminativa e/ou motivadora dos estímulos envolvidos na tarefa experimental. Sugere-se que o presente delineamento pode permitir a formulação de análises funcionais do fenômeno comportamental normalmente envolvido em alguns casos de TOC / Experimental models of obsessive compulsive disorder (OCD) with humans show that a way to evoke checking behaviors is to provide instructions that specify aversive consequences for behavior ineffective in performing tasks. Currently there is only one experimental study with a single subject design in this area. The present study presents two experiments with 16 verbally skilled participants tested whether instructions specifying the appetitive or aversive consequence could have the effect of producing checking behaviors. In an experimental restaurant, the instructions were presented during a task of separation of mixed seeds. In Experiment 1, five of eight participants showed higher percentages of checks under specification of aversive consequence. In Experiment 2, seven of eight participants had higher percentages under specification of appetitive consequence. It was concluded that certain instructions alter the discriminative and motivate function of the stimuli involved in experimental task. It is suggested that this design may allow the formulation of functional analysis of behavioral phenomenon normally involved in some cases of OCD

Estudos prévios avaliando domínios neuropsicológicos, especialmente funções executivas, indicam a presença de déficits em portadores do Transtorno Obsessivo Compulsivo (TOC). No entanto, achados neste sentido são muitas vezes contraditórios. Estas divergências podem, em parte, ser explicadas a partir de limitações metodológicas como pareamento inadequado de pacientes e controles e o uso de medicamentos no momento da avaliação neuropsicológica. Este estudo teve os seguintes objetivos: 1) verificar o funcionamento neuropsicológico, especialmente das funções executivas, de pacientes portadores de TOC sem tratamento prévio comparados a controles normais; 2) identificar fatores neuropsicológicos preditivos de resposta a tratamento com terapia cognitivo-comportamental em grupo (TCCG) ou fluoxetina. Pacientes portadores de TOC (n=50) foram pareados com controles saudáveis (n=35) por gênero, idade, escolaridade, nível socioeconômico e lateralidade manual. Estes foram avaliados a partir de uma bateria neuropsicológica investigando: quociente intelectual, funções executivas, memória verbal e não verbal, habilidades sociais e funções motoras. Os pacientes portadores de TOC foram alocados em dois subgrupos: 26 foram submetidos a tratamento medicamentoso com fluoxetina e 24 foram submetidos a um protocolo de TCCG por 12 semanas. Encontramos déficits nos pacientes portadores de TOC quando comparados a controles saudáveis quanto à flexibilidade cognitiva (segundo teste de Hayling), funções motoras (pelo teste de Grooved pegboard) e habilidades sociais (pelo inventário de Del Prette). Algumas medidas neuropsicológicas foram preditivas de melhor resposta a ambos os tratamentos: maior número de respostas corretas no teste do California verbal learning test (CVLT) (Trials 1-5); maior rapidez na parte D 14 (Dots) do Victoria stroop test (VST); maior lentidão na parte W (Word) no VST e menor número de erros na parte C (Colors) do VST (principalmente à TCCG). Maior quociente intelectual (QI) verbal se associou com melhor resposta à TCCG. Menor número de respostas perseverativas no CVLT se associou com melhor resposta à TCCG e pior resposta à medicação. Concluindo, neste estudo portadores de TOC apresentaram déficits na flexibilidade mental, habilidades sociais e funções motoras. Medidas neuropsicológicas como QI verbal, memória verbal e controle inibitório foram preditivas de resposta ao tratamento. Padrões específicos das habilidades verbais e perserveração se associaram de forma diferenciada á resposta a TCCG ou à fluoxetina. Assim, a avaliação neuropsicológica, pode auxiliar não só na indicação do melhor tratamento, mas também alertar o clínico para aqueles pacientes com maiores chances de não resposta ao tratamento de primeira escolha, nos quais medidas adicionais devem ser associadas. / Previous studies assessing neuropsychological domains, especially executive functions, indicate the presence of deficits in patients with Obsessive Compulsive Disorder (OCD). However, findings in this sense are often contradictory. These discrepancies may partly be explained by methodological limitations such as inadequate matching of patients and controls and use of medication at the time of neuropsychological assessment. This study had two aims: 1) to assess the neuropsychological functioning, especially in executive functions in OCD patients without prior treatment compared with healthy controls and 2) to identify neuropsychological predictors of response to treatment with fluoxetine or cognitivebehavioral therapy in group (CBTG). Patients with OCD (n=50) were matched with healthy controls (n=35) by gender, age, education, socioeconomic status and handedness. Patients and controls were evaluated with a neuropsychological battery investigating: intellectual quotient (IQ), executive functions, motor functions, verbal memory and non-verbal, social skills and motor function. OCD patients were allocated into two subgroups: 24 were submitted to GCBT for 12 weeks and 26 underwent treatment with fluoxetine. We found deficits in OCD patients compared to healthy controls in cognitive flexibility (Hayling test), motor functions (Grooved pegboard test) and social skills (inventory of Del Prette). Some neuropsychological measures were predictive of a better response to both treatments: greater number of correct answers on the California verbal learning test (CVLT) (Trials 1-5); greater speed on board D (Dots) of the Victoria stroop test (VST); greater slowness on board W (Word) of VST and fewer errors on the board C (Colors) of VST (primarily in TCCG). Greater verbal IQ was associated with better response to CBTG. Fewer perseveration answers in the 17 CVLT was associated with better response to CBTG and worse response to fluoxetine. In conclusion, patients with OCD showed deficits in cognitive flexibility, social skills and motor functions compared to healthy controls. Neuropsychological measures such as verbal IQ, verbal memory and inhibitory control were predictive of treatment response. Specific patterns of verbal abilities and mental flexibility predicted different treatment response to GCBT or fluoxetine. Thus, neuropsychological assessment may provide important information for treatment choice in clinical settings and may alert clinicians to those patients that are most likely non-responders, in whom additional treatment modalities should be implemented.

Os transtornos mentais na infância são prevalentes e causam prejuízo para o indivíduo, família e sociedade. Informações acerca do custo dos transtornos mentais na infância são úteis para o planejamento do sistema de saúde, para auxiliar tomadas de decisão de gestores acerca de investimentos na área e para determinação de prioridades no orçamento público. No entanto, não há dados sobre o custo dos transtornos mentais na infância no Brasil. Já dados sobre o custo dos transtornos mentais na infância em nível subclínico são inexistentes na literatura nacional e internacional. Os objetivos centrais da presente tese de doutorado, dividida em Estudo I e Estudo 11, foram: estimar a média do custo do transtorno mental na infância em níveis subclínico e clínico, e estimar o custo total destes para o Brasil. O Estudo I teve como desfecho clínico qualquer diagnóstico de transtorno mental na infância; o Estudo 11, o transtorno obsessivo- compulsivo na infância (TOC), ambos em nível subclínico e clínico. A presente pesquisa é uma avaliação econômica de custo de doença de transtornos mentais na infância com utilização de método bottom-up retrospectivo. Foi baseada em dados de prevalência de um estudo populacional transversal de 2.512 estudantes de escolas públicas de Porto Alegre e São Paulo, selecionados por meio de duas técnicas: a) seleção aleatória de crianças e b) seleção de crianças com alto fiSCO para desenvolvimento de transtornos mentais (baseado no histórico psiquiátrico familiar). Para avaliação de transtornos mentais na infância, foi utilizado o instrumento Development and Well Being Assesment (DAWBA). Os custos de doença foram estimados a partir dos seguintes componentes: tratamentos em saúde mental (uso de medicamentos, psicoterapia, hospitalização), uso de serviços sociais (assistência social, conselho tutelar, medidas socioeducativas) e problemas escolares (suspensão, abandono e repetência escolar). A amostra final foi de 2.512 crianças, de 6-14 anos de idade. Resultados do Estudo I: o transtorno mental infantil em nível subclínico e clínico teve média de custo total ao longo da vida de $1.750,86 e $3.141,21, respectivamente (todos os valores em PPP, purchasing power parity). O custo nacional estimado do transtorno mental subclínico foi de $9,92 bilhões, enquanto do transtorno mental clínico foi de $11,65 bilhões (baseado nos dados de prevalência do presente estudo). Resultados do Estudo lI: o TOC subclínico e clínico apresentaram médias de custo total ao longo da vida de $1.651,81 e $3.293,38, respectivamente. O custo nacional do TOC subclínico foi de $6,71 bilhões, enquanto do TOC clínico foi de $2,02 bilhões (baseado nos dados de prevalência do presente estudo). Os dados apresentados nesta tese de doutorado fornecem evidências de que transtornos mentais subcltnicos e clínicos na infância têm grande impacto econômico na sociedade. O conhecimento acerca do grande impacto econômico dos transtornos mentais na infância pode informar gestores e políticos sobre a magnitude do problema, de forma que seja possível planejar um sistema efetivo de cuidados com programas de tratamento e prevenção. Recomenda-se que gestores públicos aumentem os recursos para os setores da saúde e educação no Brasil, para promover prevenção e assistência em saúde mental da infância / Child mental disorders are prevalent and impairing, negatively impacting families and society. lnformation on child mental disorders costs is important to plan the health system and to show policy makers how plan and prioritize budgets. However, there are no child mental disorders cost studies in Brazil. The main objectives of the present thesis were to estimate the mean costs of subthreshold and clinical mental disorders in children living in Brazil and to estimate its national costs. Outcome of Study I was any child mental disorder, outcome of Study II was child obsessive-compulsive disorder (OCD), both subthreshold and clinical. The present study it is cost-of-illness study of child mental disorders using a retrospective bottom-up methods, based on prevalence data from a cross-sectional study of children registered at public schools in Porto Alegre and Sao Paulo. A total of 8,012 families were interviewed, providing information about 9,937 children. From this pool, two subgroups were further investigated using random- selection (n=958) and high-risk group selection procedure (n=I,514), resulting in a total sample of 2,512 subjects 6-14 years old. Mental disorder assessment was made using the Development and Well-Being Assessment (DAWBA). The cost of child mental disorders was estimated from the following components: use of mental health services, social services and school problems. Costs were estimated for each child and the economic impact at the national levei was calculated. Study I results: subthreshold and clinical disorder showed lifetime mean total cost of $1,750.86 and $3,141.21, respectively. The national lifetime cost estimate of clinical mental disorders in Brazil was $11.65 billion, whereas for subthreshold mental disorder it was $19.92 billion (alI values in PPP, purchasing power parity). Study 11: subthreshold and clínical OCD showed lifetime mean total cost of $1,651.81 and $3,293.38, respectively. The national lifetime cost estimate of clinical OCD in Brazil was $2.03 billion, whereas for subthreshold OCD it was $6.71 bilIion. The present study provides evidence about the economic impact of child mental disorders. This knowledge can inform about the magnitude of the problem, so that policy makers can make adjustments to better address these problems with cost-effective programs of treatment and prevention. It is recommended that health and education budgets in Brazil should increase to enhance prevention and treatment of children with childhood mental disorders