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Obsessive compulsive disorder (OCD) is one of the most disabling psychiatric disorder. About 10% of patients with OCD do not respond to pharmacological treatment. However, deep brain stimulation (DBS) has advanced as an alternative treatment. In 2002, two patients who suffered from co-morbidity of Parkinson’s disease (PD) and OCD were treated with DBS for their PD, with DBS-electrodes placed in the subthalamic nucleus (STN). Surprisingly, not only PD symptoms but also OCD symptoms were improved. This was the first time that patients with OCD were treated with DBS in STN and it was found to markedly improve their symptoms. When performing DBS in patients with OCD, as well as for treating PD, several side-effectshave been observed. The side-effects can be both physical and psychological. In this project,the aim is to investigate the efficiency and side-effects of DBS in OCD, correlated with the position of the electrode in, or near, the STN. To address the aim, 10 published reports were analysed. It was found that all electrode positions reported resulted in great improvement of OCD symptoms. In fact, 88% of patients had significant improvement. There was no clear correlation between position of the electrode and number or type of side-effect. However, there was a trend that patients with the electrode placed in associative/limbic STN suffered from more side-effects. In conclusion, this project demonstrates that there might be a correlation between target for electrode stimulation and side-effects. It would be interesting analyse this closer, including additional electrode target areas, but also consider other possible explanations for the variety of side-effects caused by DBS for OCD.

Obsessive-compulsive disorder (OCD) is heterogeneous. Clinical presentation of OCD differs by sex and age-of-onset and evidence supports classification based on these subtypes. The prevalence of OCD in the general population is 2%. However, it has been established that women tend to experience onset and exacerbation of OCD during reproductive milestones. In particular, the prevalence of postpartum OCD is between 4 to 9%. This study seeks to examine the effects of past childhood maltreatment and S/Lg-allele status of the 5-HTTLPR polymorphism on perinatal obsessive-compulsive symptoms and aberrant resting state functional connectivity in the postpartum period. Forty women participated in the first visit and sixteen women have been followed up with in the postpartum period. 5-HTTLPR genotype was determined from whole blood samples via polymerase chain reaction and a restriction fragment length digest. We used the Yale-Brown Obsessive-Compulsive Scale and Perinatal Obsessive-Compulsive scale to measure symptom severity. Resting state functional connectivity was determined from functional magnetic resonance imaging data. Obsessive-compulsive symptoms during late pregnancy are significantly predicted by 5-HTTLPR genotype, past history of total childhood maltreatment or childhood emotional neglect and trait anxiety symptoms. Whereas obsessive-compulsive symptoms during the postpartum period are predicted by poor sleep quality and childhood emotional maltreatment or 5-HTTLPR genotype, childhood emotional maltreatment and trait anxiety symptoms. Seed to region-of-interest analysis was employed to evaluate resting state functional connectivity differences between OCD patients and healthy controls in the postpartum period. Compared to healthy controls, OCD patients show greater connectivity between the caudate nucleus with the orbitofrontal cortex, the pars triangularis and the cingulate area. The insular cortex shows decreased connectivity between the right and left, the dorsal anterior cingulate area and the pars opercularis. The amygdala has increased connectivity with the cingulate area, the calcarine fissure, the supramarginal gyrus and decreased connectivity with the gyrus rectus. The above clinical and neuroimaging findings are in line with past work. However, this is the first study to show both 5-HTTLPR genotype and history of childhood maltreatment predict obsessive-compulsive symptoms in a perinatal population. Further, the resting state data replicates findings in the OCD literature but the study is the first to show this in postpartum women. This study serves as a platform for future work to further investigate both gene-environment interactions and distinct neuroimaging correlates in perinatal OCD. / Thesis / Master of Science (MSc)

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.

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.

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.

The study sought to explore the influence of gastrointestinal symptoms in female respondents with emetophobia disorder, panic disorder with agoraphobia and obsessive compulsive disorder. The research assessed a sample of sixty respondents which formed part of three groups which were recruited from clinical and online support groups. The age ranged from twenty to forty-five years. Non-probability quota sampling was employed. A non-experimental research design was implemented in order to make comparisons between these groups’ association of gastrointestinal symptoms and the occurrence of possible vomiting. The differential research strategy determined whether a statistically significant difference existed. The groups were assessed on the Gastrointestinal Symptom Score (2005) and the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (2004). The research aimed to determine whether empirical support exists for the Cognitive Behavioural Model of Emetophobia by Boschen (2007). / Psychology / M.A. (Psychology)

Transtornos psiquiátricos têm sido descritos com maior freqüência em pacientes com Coréia de Sydenham (CS) do que em pacientes com Febre Reumática(FR) sem CS. Os objetivos desse estudo forma o de verificar: se existe uma freqüência aumentada de transtornos psiquiátricos em pacientes com FR comparados a um grupo controle; se estes transtornos psiquiátricos apresentam freqüência aumentada em grupo de pacientes com Coréia de Sydenham, a manifestação da FR no Sistema Nervoso Central, comparado ao grupo de pacientes com FR sem CS; e, por fim, verificar a relação temporal entre o início destes diversos transtornos e o início da FR. Concluiu-se que a presença de FR está associada a uma maior freqüência de transtornos psiquiátricos, mesmo na ausência de CS. O TDHA e o TT, neste estudo, foram indicados como fatores de risco para o desenvolvimento de CS em pacientes com FR. / Psychiatric disorders have been described as more frequent in Sydenham’s Chorea patients SC) than in rheumatic fever without SC (RF). The aim of this study was to investigate it the prevalence of psychiatric disorders in RF is associated with the occurrence of SC. Furthermore, age of onset of the various symptoms was determined in order to clarify the temporal relationship between the presence of psychiatric symptoms and either rheumatic fever or Sydenham’s Chorea. Using semi-structured diagnostic interviews for DSM-IV and ratings scales, the authors assessed 22 SC patients, 20 RF patients and 20 pediatric controls. Statistical Analyses were performed using Pearson chi-square (Fischer’s exact test for 2x2 tables) for comparisons of categorial variables. Comparisons of continuous variables among groups were carried out using ANOVA and the Student t-test, when only groups were analyzed. In order to establish the risk for the development of SC and OCD given to presence of other co-morbid conditions, a logistic regression was applied. The level of significance adopted was 0.05. Both the SC and RF groups showed a greater prevalence of psychiatric disorders. The SC sample showed higher frequency of major depression disorder (MDD) (x2 = 19,1, df = 2, p = 0,00007), tic disorder (TD) (x2 = 21,1, df = 2, p = 0,00001) and attention-deficit hyperactivity disorder (ADHD) (x2-21,7, df = 2, p = 0,0002). Although Obsessive-Compulsive Disorder (OCD) was not statiscally higher in the SC and RF groups, Obsessive-Compulsive Symptoms were more frequent in both RF and SC groups compared to the controls (x2 = 7,3, df = 2, p = 0,025). The age of onset for both ADHD and TD predicted the risk for development of SC. The risk of development of OCD in SC children was also associated with the age of onset of ADHD. RF seems to confer increased risk to develop neuropsychiatric disorders even in patients without SC. In this sample, ADHD and TD was an important risk factor for the occurrence of co-morbid illnesses.

Transtornos psiquiátricos têm sido descritos com maior freqüência em pacientes com Coréia de Sydenham (CS) do que em pacientes com Febre Reumática(FR) sem CS. Os objetivos desse estudo forma o de verificar: se existe uma freqüência aumentada de transtornos psiquiátricos em pacientes com FR comparados a um grupo controle; se estes transtornos psiquiátricos apresentam freqüência aumentada em grupo de pacientes com Coréia de Sydenham, a manifestação da FR no Sistema Nervoso Central, comparado ao grupo de pacientes com FR sem CS; e, por fim, verificar a relação temporal entre o início destes diversos transtornos e o início da FR. Concluiu-se que a presença de FR está associada a uma maior freqüência de transtornos psiquiátricos, mesmo na ausência de CS. O TDHA e o TT, neste estudo, foram indicados como fatores de risco para o desenvolvimento de CS em pacientes com FR. / Psychiatric disorders have been described as more frequent in Sydenham’s Chorea patients SC) than in rheumatic fever without SC (RF). The aim of this study was to investigate it the prevalence of psychiatric disorders in RF is associated with the occurrence of SC. Furthermore, age of onset of the various symptoms was determined in order to clarify the temporal relationship between the presence of psychiatric symptoms and either rheumatic fever or Sydenham’s Chorea. Using semi-structured diagnostic interviews for DSM-IV and ratings scales, the authors assessed 22 SC patients, 20 RF patients and 20 pediatric controls. Statistical Analyses were performed using Pearson chi-square (Fischer’s exact test for 2x2 tables) for comparisons of categorial variables. Comparisons of continuous variables among groups were carried out using ANOVA and the Student t-test, when only groups were analyzed. In order to establish the risk for the development of SC and OCD given to presence of other co-morbid conditions, a logistic regression was applied. The level of significance adopted was 0.05. Both the SC and RF groups showed a greater prevalence of psychiatric disorders. The SC sample showed higher frequency of major depression disorder (MDD) (x2 = 19,1, df = 2, p = 0,00007), tic disorder (TD) (x2 = 21,1, df = 2, p = 0,00001) and attention-deficit hyperactivity disorder (ADHD) (x2-21,7, df = 2, p = 0,0002). Although Obsessive-Compulsive Disorder (OCD) was not statiscally higher in the SC and RF groups, Obsessive-Compulsive Symptoms were more frequent in both RF and SC groups compared to the controls (x2 = 7,3, df = 2, p = 0,025). The age of onset for both ADHD and TD predicted the risk for development of SC. The risk of development of OCD in SC children was also associated with the age of onset of ADHD. RF seems to confer increased risk to develop neuropsychiatric disorders even in patients without SC. In this sample, ADHD and TD was an important risk factor for the occurrence of co-morbid illnesses.

The study sought to explore the influence of gastrointestinal symptoms in female respondents with emetophobia disorder, panic disorder with agoraphobia and obsessive compulsive disorder. The research assessed a sample of sixty respondents which formed part of three groups which were recruited from clinical and online support groups. The age ranged from twenty to forty-five years. Non-probability quota sampling was employed. A non-experimental research design was implemented in order to make comparisons between these groups’ association of gastrointestinal symptoms and the occurrence of possible vomiting. The differential research strategy determined whether a statistically significant difference existed. The groups were assessed on the Gastrointestinal Symptom Score (2005) and the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (2004). The research aimed to determine whether empirical support exists for the Cognitive Behavioural Model of Emetophobia by Boschen (2007). / Psychology / M.A. (Psychology)