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Le syndrome de Gilles de la Tourette (SGT), le trouble obsessionnel compulsif (TOC) et les comportements répétitifs centrés sur le corps (CRCC) sont trois troubles qui présentent de nombreuses similarités, autant d’ordre phénoménologique que neuroanatomique et fonctionnel. Toutefois, malgré une recension des écrits pointant vers un possible spectre incluant ces trois troubles, les études qui ont contrasté ceux-ci se font peu nombreuses. Étudier les processus cognitifs affectés dans chacune de ces conditions cliniques permettrait alors d’offrir une meilleure compréhension des différences et des similarités entre celles-ci. D’ailleurs, l’utilisation des potentiels évoqués comme technique d’imagerie cérébrale offre l’avantage de mesurer l’activité cérébrale avec une excellente résolution temporelle. Les composantes de potentiels évoqués permettent alors de refléter certains processus cognitifs, notamment les processus attentionnels et mnésiques, qui sont connus comme étant potentiellement affectés dans ces trois troubles. Notre objectif était donc de comparer l’amplitude de trois composantes (P200, N200 et P300) entre des groupes de participants atteints du SGT (n=24), du TOC (n=18) et des CRCC (n=16), qui ont tous été appariés à un groupe contrôle (n=59) dans une tâche de oddball visuelle cognitive. Nos résultats n’ont d’abord montré aucune différence intergroupe pour la P200 et la N200 lorsqu’on contrôle pour les symptômes anxio-dépressifs, ce qui laisse présager que les processus cognitifs reflétés par ces composantes sont intacts dans ces populations cliniques. En ce qui a trait à la composante P300, nos résultats ont montré une diminution de l’effet oddball P300 pour les groupes SGT et TOC comparativement au groupe contrôle, alors qu’un effet oddball intact a été observé pour le groupe CRCC. Les analyses de localisation de sources ont révélé des activations dans le gyrus lingual et le gyrus occipital moyen pour le groupe TOC, ce qui le distingue des deux autres groupes cliniques et du groupe contrôle. En effet, ceux-ci ont plutôt montré des activations dans le cortex cingulaire pour la génération de cet effet oddball. Ainsi, il semblerait que les groupes SGT et TOC présentent des déficits dans la mémoire de travail, tels que dégagés par les altérations de la composante P300, mais que des régions cérébrales différentes soient impliquées dans la génération de ces activations anormales. / Tourette Syndrome (TS), Obsessive-Compulsive Disorder (OCD) and Body-Focused Repetitive Behaviors (BFRB) are three disorders that share many similarities in terms of phenomenology, neuroanatomy and functionality. However, despite a literature review pointing towards a possible spectrum including these three disorders, only a few studies compared them in the same context. Studying the cognitive processes affected by these clinical conditions would provide a better understanding of their differences and similarities. Moreover, using EventRelated Potentials (ERP) as a brain imaging technique offers the advantage of measuring brain activity with excellent temporal resolution. The ERP components can then reflect specific cognitive processes, notably attentional and memory processes, which are known to be potentially affected in these three disorders. Our aim was, therefore, to compare the amplitude of three ERP components (P200, N200, and P300) across groups of participants with TS (n=24), OCD (n=18), and BFRB (n=16), all of whom were matched to a control group (n=59), in a cognitive visual oddball task. Our results initially showed no group differences for the P200 and N200 when controlling for anxiety and depressive symptoms, suggesting that the cognitive processes reflected by these components are intact in these clinical populations. Concerning the P300 component, our results showed a decrease in the P300 oddball effect for the SGT and OCD groups compared to the control group, whereas an intact oddball effect was observed for the BFRB group. Furthermore, source localization analyses revealed activations in the lingual and middle occipital gyrus for the OCD group, distinguishing it from the other two clinical groups and the control group. Indeed, these groups showed activations in the cingulate cortex to generate this oddball effect. Thus, it seems that the TS and OCD groups show deficits in working memory, as revealed by alterations in the P300 component, but those different brain regions are involved in generating these distinct activations.

Die Zwangsstörung ist durch sehr verschiedenartige Symptome charakterisiert. Diese Symptomheterogenität stellt Herausforderungen für die psychologische Diagnostik dar. Die Yale-Brown Obsessive Compulsive Scale (Y-BOCS) gilt als der Goldstandard bei der Messung von Zwangssymptomen. Mittels einer großen Stichprobe von Zwangspatienten hatte diese Arbeit drei Ziele zur Weiterentwicklungen psychometrischer Methoden: Erstens wurden die Messmodelle von Zwangssymptomen evaluiert und verbessert. Dabei fand eine umfassende Überarbeitung statt, wobei Bayesianische Messmodelle genutzt wurden. Zweitens wurde getestet, ob die Messeigenschaften der Y-BOCS über die Zeit und für weitere klinische relevante Variablen konstant sind. In einer breit angelegten Messinvarianzanalyse wurden nur wenige Verletzungen der Messinvarianz gefunden. Falls solche vorliegen, werden Gruppenvergleiche verzerrt und eventuell falsche Schlussfolgerungen gezogen. Für diese Situationen wurde drittens eine Erweiterung partieller Messinvarianzmodelle entwickelt und angewendet. Partielle Messinvarianzmodelle ermöglichen valide Gruppenvergleiche auch dann, wenn Messinvarianz nur für einige wenige Items hält. Es wurde eine Methode zur Modellmittelung entwickelt, die die Unsicherheit berücksichtigt, die in der Auswahl von Items für partielle Messinvarianz liegt. Das entwickelte Bayesianische Verfahren macht Analyseentscheidungen komplett sichtbar und damit diskutierbar. Die vorgelegten Studien dienen der Weiterentwicklung psychometrischer Analysen in der klinischen Diagnostik im Allgemeinen und stärken die Validität der Messung durch die Y-BOCS im Besonderen. Klinische Studien können vertrauenswürdige Ergebnisse nur aufbauend auf soliden Messverfahren erzielen. Außerdem werden weitere neuere Entwicklungen in der psychometrischen Theorie im Hinblick auf ihren Nutzen in der klinischen Diagnostik und dem Verständnis der Zwangsstörung diskutiert. / Obsessive-compulsive disorder (OCD) is characterized by heterogeneous symptoms. Like for many clinical phenomena, this heterogeneity in symptoms poses challenges to psychological assessment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) has developed into a gold standard within the past three decades. Using a large sample of patients suffering from OCD, we worked towards three goals in order to advance psychometric methods: First, evaluating and improving the measurement models associated with OCD symptoms by means of an exhaustive overhaul and the usage of Bayesian measurement modeling. Second, to test whether the Y-BOCS' measurement properties are stable across time and other features relevant to clinical research. In a broad analysis of measurement invariance (MI), we found only few instances where MI did not hold. Under such circumstances, group comparisons may be biased and conclusions could be misleading. For such situations, we thirdly derived and applied a procedure extending partial MI modeling. In partial MI models, group comparisons are still valid, even if MI holds only for a few items. We developed a model averaging approach that appropriately reflects the uncertainty stemming from choosing items for partial MI models. The developed Bayesian procedure makes decisions made during the analysis fully transparent and thus open to discussion. The presented studies form a research program that advances psychometrical analyses in clinical assessment and increases the validity of the assessment of OCD by means of the Y-BOCS. Clinical trials require such sound measurements in order to provide trustworthy conclusions. Furthermore, we discuss other recent advances in the field of psychometry and their usability for clinical research as a whole and the understanding of OCD specifically.

This is a habilitation thesis submitted to and accepted by the council of the faculty of life sciences at the Humboldt-Universität zu Berlin, Berlin, Germany. The thesis is written in English, but some formal parts (e.g., on the title page) and acknowledgements are written in German language. / Die Research-Domain-Criteria-Initiative und andere haben vorgeschlagen, zur Konzeption psychischer Störungen dimensionale psychologische Konstrukte zu verwenden. Die vorliegende Arbeit beschreibt mehrere Experimente, in denen mit Augenbewegungsaufgaben das Konstrukt der kognitiven Kontrolle evaluiert wurde. Die Studien sollten klären, welche kognitiven und neuronalen Mechanismen zu den bei Menschen mit Schizophrenie oder Zwangsstörung erhöhten Latenzen volitionaler Sakkaden beitragen. In drei Studien wurden Anforderungen der Antisakkadenaufgabe isoliert und funktionelle Magnetresonanztomographie angewendet. Die Ergebnisse legen nahe, dass die verlangsamte volitionale Sakkadengenerierung bei Schizophrenie durch eine dysfunktionale Aktivierung des lateralen präfrontalen Cortex und der supplementären Augenfelder vermittelt wird, was mit Defiziten in der proaktiven Handlungskontrolle verbunden sein könnte. Fünf weitere Experimente sollten Teilprozesse aufklären und haben gezeigt, dass die Defizite möglicherweise aus einer Beeinträchtigung der volitionalen Loslösung der Fixation und der motorischen Vorbereitung resultieren. Zwei weitere Studien legen nahe, dass auch die Zwangsstörung mit erhöhten Latenzen volitionaler Sakkaden assoziiert ist. Effekte experimenteller Variation haben jedoch gezeigt, dass diesen Defiziten wahrscheinlich eine Verlangsamung der Reaktionsauswahl zugrundeliegt. Die bei beiden Patientengruppen vermutlich betroffenen Mechanismen dienen zielgerichteten Verhaltensweisen. Man kann vermuten, dass die Defizite eine Störung auf der Ebene eines allgemeinen Faktors exekutiver Funktionen widerspiegeln. Die experimentellen Ergebnisse weisen jedoch auch auf störungsspezifische Funktionsbeeinträchtigungen hin. Zukünftige Forschung muss den Zusammenhang zwischen diesen Beeinträchtigungen und Symptomen besser aufzuklären, wenn Konzepte psychischer Störungen, die auf experimentell definierten psychologischen Konstrukten basieren, am Ende erfolgreich sein sollen. / The research domain criteria initiative and others have suggested to conzeptualize mental disorders on the basis of dimensional psychological constructs. The present work describes several experiments using eye movement tasks to evaluate the construct of cognitive control. The studies aimed at uncovering cognitive and neural mechanisms involved in increased latencies of volitional saccades as found in individuals with schizophrenia or obsessive-compulsive disorder. Three studies used functional magnetic resonance imaging and isolated different demands of the antisaccade task. The results suggest that slowed volitional saccade generation in schizophrenia is mediated by dysfunctional activation of the lateral prefrontal cortex and the supplementary eye fields, which may relate to deficits in proactive control of action. Five additional behavioral experiments aimed at specifying sub-processes and showed that the deficits might result from impairments in volitional fixation disengagement and motor preparation. Two studies in individuals with obsessive-compulsive disorder suggest that this disorder is also associated with increased latencies of volitional saccades. However, experimental variation revealed that these deficits may reflect a slowing in response selection. The mechanisms affected in both groups are serving goal-directed behaviors and may reflect a disturbance on the level of a common executive functions factor. However, the experimental results also suggest disorder specific functional impairment. Future research will have to improve our understanding of the relationship between these impairments and symptoms if concepts based on experimentally defined psychological constructs shall be successful in the end.

Il s'agit d'une hypothèse largement répandue que l’égo-dystonie et l’égo-syntonie caractérisent les obsessions dans les troubles des conduites alimentaires (TCA) et que ces facteurs sont cliniquement pertinents pour la conceptualisation et le traitement des TCA. Cependant, les résultats empiriques sur ce sujet sont rares. Compte tenu du chevauchement reconnu entre les TCA, notamment l'anorexie et la boulimie (BN), et le trouble obsessionnel-compulsif (TOC) dans la phénoménologie et les caractéristiques psychologiques, un programme de thérapie cognitive basée sur les inférences (TBI) de 24 semaines, démontré efficace dans le traitement des TOC, a été adapté pour traiter les TCA. La recherche sur le TOC suggère que la transformation des pensées intrusives en obsessions est liée à la mesure dans laquelle les pensées intrusives menacent des perceptions fondamentales du soi et de l’identité. Cette thèse a pour objectif d'examiner le lien entre l’égo-dystonie et les TCA. Pour se faire, nous avons exploré le lien entre la nature égo-dystone des obsessions chez les patients souffrant d'un TCA et la peur de l'image de soi. Nous avons également étudié la relation entre la sévérité des symptômes TCA et l’égo-dystonie dans les obsessions. En outre, nous avons investigué les différences dans la présence de pensées égo-dystones et de peur face à son identité entre des sujets non-cliniques et des personnes atteintes d’un TCA. Enfin, nous avons comparé le degré d’égo-dystonie dans les pensées de personnes atteintes d’un TCA à celui dans les pensées d’individus souffrant d’un TOC. L’égo-dystonie dans les pensées a été mesurée par l'Ego Dystonicity Questionnaire (EDQ) et le degré de peur face à l’identité a été mesuré par le Fear of Self Questionnaire (FSQ) d’une part dans un échantillon de femmes souffrant d’un TCA (n = 57) et d’autre part dans un échantillon de participantes non-cliniques (n = 45). Les résultats révèlent que l’égo-dystonie et la peur face à l’identité étaient fortement corrélées à la fois dans l’échantillon clinique et non-clinique. Les scores de l’EDQ n’étaient pas significativement corrélés à la sévérité des symptômes TCA à l'exception de la sous-échelle d’irrationalité de l’EDQ qui était fortement associée à la sévérité des comportements compulsifs compensatoires. Les participantes souffrant d'un TCA avaient des scores significativement plus élevés à l’EDQ et au FSQ que les sujets non-cliniques. Ensuite, une étude de cas décrit l’application du programme de thérapie cognitive TBI pour une femme de 35 ans avec un diagnostic de BN. La pathologie TCA s’est significativement améliorée au cours de la TBI et six mois suivant la thérapie. Cette étude de cas met en évidence l'importance de cibler les idées surévaluées, les doutes et le raisonnement face au soi et à l’identité dans le traitement psychologique pour les TCA. Enfin, l’objectif final de cette thèse était d’examiner les changements au niveau (1) des symptômes TCA, (2) du degré d’égo-syntonie dans les obsessions, et (3) des mesures de peur face à l’identité, de motivation, d’humeur et d’anxiété au cours de la TBI et au suivi post six mois. L’égo-dystonie, la peur face à l’identité, les symptômes TCA et le stade motivationnel ont été mesurés chez 15 femmes souffrant de BN au cours du traitement et six mois après la TBI. Quatre vingt pourcent de l’échantillon, soit 12 des 15 participantes, ont démontré une diminution cliniquement significative des symptômes TCA et 53% ont cessé leurs comportements compensatoires au suivi post six mois. Les retombées cliniques relatives au traitement des TCA sont discutées. / There is a widely held assumption that both ego-dystonicity and ego-syntonicity characterize obsessions in eating disorders (EDs), and these factors are clinically relevant to the conceptualization and treatment of EDs; however, empirical findings on this subject are scarce. Given the recognized overlap between EDs, particularly anorexia and bulimia nervosa (BN), and obsessive-compulsive disorder (OCD) in phenomenology and psychological characteristics, a 24-week cognitive inference-based therapy (IBT) program shown to be effective in treating OCD was adapted to treat EDs. OCD research has suggested that the transformation of intrusive thoughts into obsessions is linked to the degree to which intrusive thoughts threaten core perceptions of the self. The present thesis aims to examine the relationship between ego-dystonicity and EDs. To do so, we explored the link between the ego-dystonic nature of obsessions in patients suffering from an ED and fear of self concept. We also investigated the relationship between ED symptom severity and ego-dystonicity in obsessions. Moreover, we studied differences between non-clinical and eating-disordered individuals in the presence of ego-dystonic thoughts and extent of fear of self. Finally, we compared the degree of ego-dystonicity in individuals with EDs’ thoughts to those suffering from OCD. Ego-dystonicity in thoughts was measured by the Ego Dystonicity Questionnaire (EDQ) and degree of feared self was measured by the Fear of Self Questionnaire (FSQ) in both a clinical sample (n = 57 women with EDs) and a non-clinical female sample (n = 45). Ego-dystonicity and fear of self were highly correlated in both clinical and non-clinical samples. EDQ scores were not significantly correlated to overall ED symptom severity with the exception of the EDQ Irrationality subscale, which was related strongly to ED compulsion (ritual) severity. Participants suffering from an ED had significantly higher EDQ scores and FSQ scores compared to controls. Next, a case study describes the application of IBT treatment for a 35-year-old woman diagnosed with BN. ED pathology significantly decreased from pre-IBT to six-month follow-up. This case study highlights the importance of addressing overvalued ideas, fear of self and self-doubt in psychological treatment for EDs via a focus on self-cognitions and reasoning about self. Furthermore, the final objective of this thesis was to examine the change in (1) ED symptom severity, (2) the degree of ego-dystonicity in obsessions, and (3) fear of self, motivational, mood and anxiety measures from pre-IBT to six-month follow-up. Ego-dystonicity, fear of self, ED symptoms and motivational stage were assessed in 15 women with BN over the course of IBT and at follow-up. Eighty percent of the sample demonstrated a clinically significant reduction in ED symptoms and 53% ceased their compensatory behaviors at six-month follow-up. Clinical implications relevant to the treatment of EDs are discussed.

São cada vez mais freqüentes as queixas cosméticas na sociedade contemporânea objetivando a perfeição das formas do corpo e da pele. Os dermatologistas e cirurgiões plásticos são frequentemente consultados para avaliar e tratar essas queixas. Sendo assim é importante conhecer o Transtorno Dismórfico Corporal, inicialmente chamado de dismorfofobia que foi pouco estudado até recentemente. Esse transtorno é relativamente comum, por vezes incapacitante, e envolve uma percepção distorcida da imagem corporal caracterizada pela preocupação exagerada com um defeito imaginário na aparência ou com um mínimo defeito corporal presente. A maioria dos pacientes apresenta algum grau de prejuízo no funcionamento social e ocupacional e como resultado de suas queixas obsessivas com a aparência podem desenvolver comportamentos compulsivos, em casos mais graves há risco de suicídio. O nível de juízo crítico é prejudicado, não reconhecem que seu defeito é mínimo ou inexistente e freqüentemente procuram tratamentos cosméticos para um transtorno psíquico. A prevalência do transtorno na população geral é de 1 a 2% e em pacientes dermatológicos e de cirurgia cosmética de 2,9 a 16%. Neste estudo investigou-se a prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos. Entrevistadores treinados avaliaram com questionários e entrevistas semi-estruturadas (SCID) pacientes que procuravam tratamentos cosméticos clínicos e cirúrgicos (grupo Cosmiatria, n=150), que procuravam a dermatologia em geral (grupo Geral, n=150) e grupo controle de 50 pacientes. Três psiquiatras independentes fizeram a melhor estimativa diagnóstica (best estimate diagnosis). Foram diagnosticados 32 pacientes (Cosmiatria 14%; Geral 6,7%; Controle 2%). As diferenças entre as prevalências nos três grupos foram significativas, bem como entre o grupo da Cosmiatria e o Controle. A regressão logística mostrou maior prevalência na Cosmiatria do que no grupo Geral e Controle, em indivíduos solteiros e com menor índice de massa corpórea. A gravidade foi moderada (em escala validada) e as obsessões foram mais significativas no grupo da Cosmiatria do que no Geral. A aplicação de escala de avaliação de crenças mostrou que o nível de juízo crítico estava mais prejudicado nos pacientes do grupo da Cosmiatria. Nenhum paciente havia sido diagnosticado previamente. As comorbidades psiquiátricas foram freqüentes, principalmente o Transtorno Depressivo Maior e o Transtorno Obsessivo Compulsivo. A comparação de subgrupos de pacientes que tinham o Transtorno Dismórfico Corporal ou este associado ao Transtorno Obsessivo-Compulsivo não mostrou diferenças significativas quanto às variáveis demográficas, comorbidades psiquiátricas, gravidade do transtorno ou nível de juízo crítico. As queixas dermatológicas mais freqüentes, em média duas, foram: discromias, acne, quanto à forma do corpo e ao envelhecimento. No grupo Cosmiatria a maioria dos pacientes já havia se submetido a tratamentos ou cirurgias cosméticas com resultados insatisfatórios. Os achados desse estudo apontam para uma maior prevalência em pacientes dermatológicos, principalmente nos que procuram tratamentos cosméticos, sugerindo que possam ser mais obsessivos e ter pior nível de juízo crítico em relação aos seus sintomas. Considerando a alta prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos e que os tratamentos cosméticos raramente melhoram seus sintomas, o treinamento dos profissionais para a investigação sistemática, diagnóstico e encaminhamento para tratamento psiquiátrico parece fundamental / Cosmetic concerns are increasingly pervading the contemporary societies, focusing on body shape and the skin perfection. Dermatologists and plastic surgeons are frequently consulted to evaluate and treat these concerns. Therefore it is important to be aware of the Body Dysmorphic Disorder, also known as dysmorphophobia, little studied until recently. This disorder is relatively common sometimes causing impairment involving a distorted perception of the body image characterized by an excessive preoccupation with an imagined or minimal appearance defect. Most of the patients experience some degree of impairment in social or occupational functioning and as a result, their obsessive thoughts, may lead to repetitive behaviors and in severe cases, to attempted suicide. Most individuals have poor insight and they do not acknowledge the defect is minimal or inexistent and seek out cosmetic treatments for a psychiatric disorder. The prevalence of this disorder among general population ranges from 1 to 2 % and in dermatological and cosmetic surgery patients ranges from 2, 9 to 16%. This study assessed the prevalence of Body Dysmorphic Disorder in dermatological patients. Trained interviewers used questionnaires (BDDQ) and semi-structured clinical interviews (SCID) to access patients seeking clinical or surgical cosmetic treatments (Cosmetic group, n=150), seeking dermatology in general (General group, n=150) and a control group of 50 subjects. Three independent psychiatrists assigned the best estimate diagnosis and 32 patients were diagnosed with the disorder (Cosmetic 14%, General 6, 7% and Control 2%). Prevalence differences in the three groups were significant, also for Cosmetic and Control groups. In the logistic regression a higher prevalence has been noticed in the Cosmetic group (when compared with General and Control groups), in patients that are not currently married and with less body mass index. The severity of the symptoms assessed by a validated scale (BDD-YBOCS) was moderate and the obsessions were significantly higher in the Cosmetic group as compared to the General one. Beliefs were assessed by a scale (BABS) and insight were significantly poorer in the Cosmetic group. None of the patients had been previously diagnosed. Psychiatric co-morbidities were frequent, mostly Major Depressive Disorder and Obsessive-Compulsive Disorder. Comparing two patients subgroups with just Body Dysmorphic Disorder and patients with Obsessive-Compulsive Disorder as comorbidity show no differences according to demographic variables, Axis I psychiatric comorbidity, symptoms severity and level of insight. The most frequent dermatological concerns were dyschromias, acne, the shape of the body and ageing. In the Cosmetical group most of the patients have performed clinical or surgical cosmetic treatments with poor results. Our findings provide further support for higher prevalence of Body Dysmorphic Disorder in dermatological patients, mainly those seeking cosmetic treatments and suggests that those patients might be more obsessive and having poorer insight into their symptoms. Taking into account the high prevalence of Body Dysmorphic Disorder in dermatological patients and cosmetic treatments that rarely improve symptoms there are compelling reasons for training professionals to systematically investigate, diagnose and refer these patients to adequate psychiatric treatment

São cada vez mais freqüentes as queixas cosméticas na sociedade contemporânea objetivando a perfeição das formas do corpo e da pele. Os dermatologistas e cirurgiões plásticos são frequentemente consultados para avaliar e tratar essas queixas. Sendo assim é importante conhecer o Transtorno Dismórfico Corporal, inicialmente chamado de dismorfofobia que foi pouco estudado até recentemente. Esse transtorno é relativamente comum, por vezes incapacitante, e envolve uma percepção distorcida da imagem corporal caracterizada pela preocupação exagerada com um defeito imaginário na aparência ou com um mínimo defeito corporal presente. A maioria dos pacientes apresenta algum grau de prejuízo no funcionamento social e ocupacional e como resultado de suas queixas obsessivas com a aparência podem desenvolver comportamentos compulsivos, em casos mais graves há risco de suicídio. O nível de juízo crítico é prejudicado, não reconhecem que seu defeito é mínimo ou inexistente e freqüentemente procuram tratamentos cosméticos para um transtorno psíquico. A prevalência do transtorno na população geral é de 1 a 2% e em pacientes dermatológicos e de cirurgia cosmética de 2,9 a 16%. Neste estudo investigou-se a prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos. Entrevistadores treinados avaliaram com questionários e entrevistas semi-estruturadas (SCID) pacientes que procuravam tratamentos cosméticos clínicos e cirúrgicos (grupo Cosmiatria, n=150), que procuravam a dermatologia em geral (grupo Geral, n=150) e grupo controle de 50 pacientes. Três psiquiatras independentes fizeram a melhor estimativa diagnóstica (best estimate diagnosis). Foram diagnosticados 32 pacientes (Cosmiatria 14%; Geral 6,7%; Controle 2%). As diferenças entre as prevalências nos três grupos foram significativas, bem como entre o grupo da Cosmiatria e o Controle. A regressão logística mostrou maior prevalência na Cosmiatria do que no grupo Geral e Controle, em indivíduos solteiros e com menor índice de massa corpórea. A gravidade foi moderada (em escala validada) e as obsessões foram mais significativas no grupo da Cosmiatria do que no Geral. A aplicação de escala de avaliação de crenças mostrou que o nível de juízo crítico estava mais prejudicado nos pacientes do grupo da Cosmiatria. Nenhum paciente havia sido diagnosticado previamente. As comorbidades psiquiátricas foram freqüentes, principalmente o Transtorno Depressivo Maior e o Transtorno Obsessivo Compulsivo. A comparação de subgrupos de pacientes que tinham o Transtorno Dismórfico Corporal ou este associado ao Transtorno Obsessivo-Compulsivo não mostrou diferenças significativas quanto às variáveis demográficas, comorbidades psiquiátricas, gravidade do transtorno ou nível de juízo crítico. As queixas dermatológicas mais freqüentes, em média duas, foram: discromias, acne, quanto à forma do corpo e ao envelhecimento. No grupo Cosmiatria a maioria dos pacientes já havia se submetido a tratamentos ou cirurgias cosméticas com resultados insatisfatórios. Os achados desse estudo apontam para uma maior prevalência em pacientes dermatológicos, principalmente nos que procuram tratamentos cosméticos, sugerindo que possam ser mais obsessivos e ter pior nível de juízo crítico em relação aos seus sintomas. Considerando a alta prevalência do Transtorno Dismórfico Corporal em pacientes dermatológicos e que os tratamentos cosméticos raramente melhoram seus sintomas, o treinamento dos profissionais para a investigação sistemática, diagnóstico e encaminhamento para tratamento psiquiátrico parece fundamental / Cosmetic concerns are increasingly pervading the contemporary societies, focusing on body shape and the skin perfection. Dermatologists and plastic surgeons are frequently consulted to evaluate and treat these concerns. Therefore it is important to be aware of the Body Dysmorphic Disorder, also known as dysmorphophobia, little studied until recently. This disorder is relatively common sometimes causing impairment involving a distorted perception of the body image characterized by an excessive preoccupation with an imagined or minimal appearance defect. Most of the patients experience some degree of impairment in social or occupational functioning and as a result, their obsessive thoughts, may lead to repetitive behaviors and in severe cases, to attempted suicide. Most individuals have poor insight and they do not acknowledge the defect is minimal or inexistent and seek out cosmetic treatments for a psychiatric disorder. The prevalence of this disorder among general population ranges from 1 to 2 % and in dermatological and cosmetic surgery patients ranges from 2, 9 to 16%. This study assessed the prevalence of Body Dysmorphic Disorder in dermatological patients. Trained interviewers used questionnaires (BDDQ) and semi-structured clinical interviews (SCID) to access patients seeking clinical or surgical cosmetic treatments (Cosmetic group, n=150), seeking dermatology in general (General group, n=150) and a control group of 50 subjects. Three independent psychiatrists assigned the best estimate diagnosis and 32 patients were diagnosed with the disorder (Cosmetic 14%, General 6, 7% and Control 2%). Prevalence differences in the three groups were significant, also for Cosmetic and Control groups. In the logistic regression a higher prevalence has been noticed in the Cosmetic group (when compared with General and Control groups), in patients that are not currently married and with less body mass index. The severity of the symptoms assessed by a validated scale (BDD-YBOCS) was moderate and the obsessions were significantly higher in the Cosmetic group as compared to the General one. Beliefs were assessed by a scale (BABS) and insight were significantly poorer in the Cosmetic group. None of the patients had been previously diagnosed. Psychiatric co-morbidities were frequent, mostly Major Depressive Disorder and Obsessive-Compulsive Disorder. Comparing two patients subgroups with just Body Dysmorphic Disorder and patients with Obsessive-Compulsive Disorder as comorbidity show no differences according to demographic variables, Axis I psychiatric comorbidity, symptoms severity and level of insight. The most frequent dermatological concerns were dyschromias, acne, the shape of the body and ageing. In the Cosmetical group most of the patients have performed clinical or surgical cosmetic treatments with poor results. Our findings provide further support for higher prevalence of Body Dysmorphic Disorder in dermatological patients, mainly those seeking cosmetic treatments and suggests that those patients might be more obsessive and having poorer insight into their symptoms. Taking into account the high prevalence of Body Dysmorphic Disorder in dermatological patients and cosmetic treatments that rarely improve symptoms there are compelling reasons for training professionals to systematically investigate, diagnose and refer these patients to adequate psychiatric treatment

This thesis extends the understanding of the neural and neurochemical contributions to two forms of behavioural adaptation, reversal learning and contingency degradation, in which stimulus/action-reward contingencies are altered. The results are interpreted within the psychological framework of the compulsivity construct, and their implications for the pathological behaviour of obsessive-compulsive-disorder (OCD) are considered. The orbitofrontal cortex (OFC) and striatum are key brain structures involved in reversal learning, as are the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) within those respective regions. However, there has been little empirical evidence of how these two structures and neurochemical systems interact, especially in the functional context of reversal learning. In Chapter Three, the impact of experimentally-induced reductions of 5-HT in the anterior OFC on monoamine levels in subcortical structures such as the striatum and amygdala was determined, DA being found to be significantly up-regulated in the amygdala. Functionally, 5-HT depletion of the OFC has previously been shown to induce deficits in reversal learning. To determine the possible causal significance of amygdala dopamine up-regulation for said reversal learning deficit, the effects of blocking the upregulation with the infusion of intra amygdala DA receptor antagonists following bilateral OFC 5-HT depletion were investigated in a reversal learning paradigm. In Chapter Four, the differential roles of regions of striatum were examined in visual reversal learning. Two recent investigations in non-human primates highlighted the role of the striatum in reversal learning,but pinpointed the critical region to be either the ventromedial caudate or the putamen. Marmosets were trained on a serial reversal task that allowed multiple acute neural manipulations, and the ventromedial caudate and putamen were then reversibly inactivated using the GABAA agonist muscimol. Results indicated dose-related impairments specifically in reversal learning within the putamen, with sparing of discrimination retention. By contrast, similar reversible inactivation of the caudate nucleus produced marked deficits in visual discrimination performance (retention). In Chapter Five, the neural basis of action-outcome contingency knowledge was investigated by inactivating distinct regions of the PFC, the perigenual ACC (pgACC; area 32) and the anterior OFC, and determining response sensitivity to the degradation of action-outcome contingencies. In previous work, excitotoxic lesions of either the pgACC or the OFC had been found to induce insensitivity to contingency degradation in marmosets. However, the design of that experiment did not allow specification of whether stimulus- or action-outcome associations were disrupted, and a precise neural locus could not be determined for the behavioural effects as the OFC lesions included parts of the lateral and medial OFC. I therefore developed a novel contingency degradation paradigm that distinguished between stimulus- and action-outcome associations to enable the study of acute pharmacological manipulations in both brain regions. The pgACC and OFC were reversibly inactivated using GABAA-GABAB agonists (muscimol-baclofen). Whereas the pgACC inactivation produced selective deficits in sensitivity to action-outcome contingency degradation, OFC inactivation reduced the suppressive effect of noncontingent reward on responding more generally but left intact sensitivity to degradation of the contingencies. These results are discussed in terms of different theories of the functions of the pgACC and OFC. In the final discussion the findings on the neural substrates of reversal learning and contingency degradation are drawn together in terms of their significance for theories of PFC involvement in cognitive control, and for the understanding of OCD and other neuropsychiatric disorders.

O transtorno obsessivo-compulsivo (TOC) é um transtorno psiquiátrico que acomete cerca de 1 a 3,1% das pessoas ao longo da vida. Embora o seu modelo neurobiológico ainda não esteja completamente estabelecido, inúmeras evidências apontam para áreas relacionadas ao circuito córtico-estriado-pálido-talâmico-cortical (CEPTC). Em especial, o córtex órbito-frontal (COF) é uma região que desempenha um papel fundamental dentro da hipótese fisiopatológica do TOC. Paralelamente, esta região já foi associada, em sujeitos saudáveis, com a habilidade de utilização espontânea da estratégia de agrupamento semântico na memorização de palavras - o que facilita sua evocação posterior. Ao mesmo tempo, estudos neuropsicológicos evidenciaram que pacientes com TOC apresentam déficits na memória episódica verbal (MEV) e que tais déficits poderiam ser mediados por dificuldades em funções executivas ligadas ao planejamento, como utilização de estratégias. Portanto, para testar a hipótese de que há diferenças no correlato neural da codificação da MEV entre pacientes com TOC e controles saudáveis, foi utilizado um teste neuropsicológico adaptado para ressonância magnética funcional (RMf): o paradigma tinha apresentação em bloco. O objetivo do presente estudo foi investigar a etapa de codificação da MEV e a capacidade de agrupamento semântico espontâneo em crianças e adolescentes com TOC. Assim, o paradigma foi constituído por duas listas de palavras: uma, semanticamente relacionada (SR), na qual as palavras eram divididas em categorias semânticas e outra, não relacionada (NR), na qual não havia relação aparente entre as palavras. O contraste de maior interesse do estudo foi a diferença entre essas duas condições (SR > NR). O nível de agrupamento semântico foi quantificado por um índice semântico. Os grupos foram formados por 25 crianças e adolescentes com TOC e 25 controles saudáveis, pareados por sexo, idade, escolaridade, preferência manual e QI. Embora os grupos estivessem pareados por essas características, eles se diferiram em sintomas clínicos, tais como sintomas de depressão, ansiedade e necessidade de rotina por parte da criança/adolescente. Os resultados comportamentais do teste de MEV mostraram que os grupos não se diferenciaram: ambos evocaram a mesma quantidade de palavras e não apresentaram diferenças no índice semântico. Apesar disso, a comparação entre os grupos - controlada para variáveis clínicas - revelou menor ativação (sinal BOLD) nos pacientes em diversas regiões cerebrais: frontais, parietais e occipito-temporais. Por outro lado, a análise de interação psicofisiológica (PPI) revelou que os pacientes apresentaram um aumento da conectividade do COF com regiões temporais em relação aos controles. Isso ocorreu para três das quatro regiões de interesse que foram posicionadas no COF: lateral e medial de ambos os hemisférios. Além disso, o grupo de pacientes apresentou uma correlação positiva entre o índice semântico e o efeito BOLD no COF, o que não ocorreu para o grupo controle. Esses resultados indicam diferenças no funcionamento cerebral de crianças e adolescentes com TOC tanto em regiões que estão dentro do modelo neurobiológico proposto para o TOC (circuito CEPTC), como fora dele também. De acordo com os resultados do presente estudo, as diferenças de ativação e de conectividade poderiam ser consideradas como um déficit latente, uma vez que ambos os grupos apresentaram o mesmo desempenho no paradigma / The obsessive-compulsive disorder (OCD) is a psychiatric disorder that affects 1-3.1% of the general population (lifetime rate). Although its neurobiological model has not been completely establish, numerous evidences indicate that areas of the cortico-striatalpale- thalamic-cortical (CSPTC) circuit are engaged in the disease. In particular, the orbitofrontal cortex (OFC) is a region that plays a key role in the pathophysiological hypothesis of OCD. In parallel to this, in healthy controls this region has been associated with the ability of using spontaneous strategies of semantic clustering at the encoding of related words - in a way that facilitates the posterior retrieval of these words. At the same time, neuropsychological studies showed that OCD patients present verbal episodic memory (VEM) deficits, and that these deficits could be mediated by executive dysfunction - like planing and utilization of strategies. Thus, to investigate the hypothesis that there are differences at the neural correlates of VEM encoding between children and adolescents with OCD and healthy controls, we used a blocked design functional Magnetic Resonance Imaging (fMRI) paradigm to evaluate both groups. The main objective of the study was to investigate the VEM encoding and the ability to spontaneously organize words according to their semantic categories. In order to do this, the fMRI paradigm consisted of two kinds of word lists: a semantically related list (SR), in which words were divided into semantic categories and a unrelated list (UR), were there was no apparent relationship between the words. However, the contrast of most interest of this study, was the difference between the conditions (\'SR > UR\'). The semantic clustering level was quantified by a semantic clustering index. Groups were constituted by 25 children and adolescents with OCD and 25 healthy controls paired by gender, age, educational level, handedness and IQ. Although both groups were matched for these characteristics, they differed in clinical symptoms such as depression, anxiety and routines. Behavioral results showed that the groups were similar in terms of retrieved words and semantic index. Nevertheless, the comparison between groups - controlled for clinical variables - showed less activation (BOLD signal) in patients in several brain regions: frontal, parietal and occipito-temporal. On the other hand, the psychophysiological interaction analysis (PPI) revealed that patients have had an increase in the OFC connectivity with the temporal regions. This has occurred in three of the four regions of interest that were placed in the OFC: lateral and medial of both hemispheres. Also, the patients showed a positive correlation between the semantic index and the BOLD effect in the OFC, which was not observed in the control group. These results suggest that there are differences in brain functioning of children and adolescents with OCD in regions that are inside/outside of the neurobiological model for OCD (CSPTC circuit). In accordance with the present results, these differences in brain activation and connectivity could be regarded as a latent deficit, since both groups presented the same behavioral performance

本研究旨在探討「健康、性格、習慣量表(HPH)」的臨床效度。HPH最初是由柯永河教授(民84)編製，後來廣泛使用在國內臨床場域中。發展至今已有中上程度的信效度支持，但過去較缺乏臨床上區辨與構念效度的研究，因此本研究旨在探討HPH區辨不同疾患的能力，以及以臨床疾患為受試時量尺之構念效度。 本研究回顧國內外類似測驗─MMPI、KMHQ、MCMI─的發展軌跡，並參照前人作法來進行HPH的臨床區辨效度研究。初步以臨床場域中常見的精神分裂症、重鬱症、低落型情感疾患、焦慮疾患，共257名患者為受試。先以共變數分析(ANCOVA)探討控制人口與臨床變項後，不同疾患組別在HPH的A、B、D類量尺的影響。再進一步使用羅吉斯迴歸(logistic regression)探討哪些量尺及其組合可以區辨兩兩疾患間的差異。最後，本研究也進行HPH的探索性因素分析(exploratory factor analysis)，以檢驗其臨床上的因素結構。 本研究發現，精神分裂症(A1)、躁症傾向(A2)、憂鬱自殺類(A3、B4、A4)、心理功能與健康(D1、D3、D4、D5、D6)量尺在共變數分析上的差異情形與假設大致相符，後續討論分析也支持強迫症(B5)量尺效度。羅吉斯迴歸中，A1、A3、B4、B5能在兩兩疾患間區辨有顯著預測力。其中A1能在精神分裂症與其他三組疾患的兩兩區辨中預測，A3能在重鬱症與另外兩組(精神分裂症、焦慮症)的兩兩區辨中預測，B4能在低落型情感與精神分裂症的兩兩區辨中預測，B5能在強迫症與其他疾患間的兩兩區辨中預測。但是在重鬱症與低落型情感疾患間，以及低落型情感與焦慮疾患間，沒有量尺能在兩者的區辨中有顯著預測力。而各兩兩疾患間整體區辨效果有中至高度的關聯性，分類正確率也多有七成以上，顯示HPH量表在臨床上的區辨效度獲得支持。 構念效度部分，A、D類量尺因素結構與當初編製的每個量尺構念相近，B類量尺構念雖與原量尺略有不同，但仍不違背原量尺編製架構，因此構念效度亦獲得支持。不過各量尺仍有值得編修之處，討論一節中針對結果提出HPH後續編修之建議。 最後，本研究也將此結果之臨床實務應用於討論一節中詳述，以供後續研究與實務者參考。 / The purpose of this study is to examine the clinical validity of the Health, Personality, and Habit Test (HPH). The HPH was developed by Dr. Yung-Ho Ko in 1995, and has been widely used in clinical settings. The HPH has demonstrated appropriate reliability and validity, but little research has been done on its differential and construct validity in the clinical settings. Therefore, the aim of this study is to explore the HPH’s ability to differentiate between disorders and its construct validity in clinical context. This research reviewed the developments of similar tests, such as MMPI, KMHQ, and MCMI, and examined validity of the HPH with the same methods. Subjects were 257 patients who suffered from common disorders in clinical settings, including schizophrenia, major depression, dysthymia, and anxiety disorders. ANCOVA was first used to explore whether different disorders have an effect on category A, B, and D scales after controlling demographic and clinical variables. Next, logistic regression was used to clarify which scales and combinations can differentiate between two of four disorders. Finally, exploratory factor analysis was conducted to examine the structure of HPH in clinical setting. The results of ANCOVA showed that the differences of schizophrenia scale (A1), manic scale (A2), depression/suicide scales (A3, B4, & A4), obsessive-compulsive disorder (OCD) scale (B5), and psychological function and health scales (D1, D3, D4, D5, D6) were partly consistent with assumptions, supporting the differential validity of HPH. The results of logistic regression analysis also supported the validity of A1, A3, B4, and B5 scales. More specifically, A1 was able to differentiate schizophrenia from any other three disorders, A3 was able to differentiate MDD from schizophrenia and anxiety disorders, B4 was able to differentiate dysthymia from schizophrenia, and B5 was able to differentiate OCD from other disorders. However, none of the scales was able to differentiate MDD from dysthymia, nor were they able to differentiate dysthymia from anxiety disorders. Moreover, each of the logistic regression functions showed moderate to high correlations, and most of them achieved high overall hit rates (above 70%), providing support for the clinical differential validity of the HPH. As for construct validity, these factors in category A and D scales were essentially similar to original scales. Similarly, factors in category B scales were compatible to original scales though difference was found. In sum, these results lent support to the construct validity of the HPH in the clinical settings. However, refining of the scales is needed and suggestions are discussed. Finally, the practical uses of the findings were also discussed.