Oxytocin Receptor Gene DNA Methylation: A Biomarker of Treatment Response in Obsessive-Compulsive Disorder?

INTRODUCTION: Obsessive-compulsive disorder (OCD) is associated with high chronicity and treatment resistance, indicating the need for early therapy response markers enabling fast and personalized treatment adaptations. Although epigenetic mechanisms such as DNA methylation of the oxytocin receptor (OXTR) gene have previously been linked to OCD pathogenesis, epigenetic markers as predictors of treatment success have not yet been investigated in OCD. OBJECTIVE: For the first time, this therapyepigenetic study aimed to investigate the role of OXTR methylation as a treatment response marker in OCD. METHODS: In total, 113 inpatients with OCD (57 females) were compared to 113 age- and sex-matched healthy controls. Patients were investigated over a 10-week course of standardized, OCD-specific cognitive-behavioral psychotherapy. Clinical response was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline, before in vivo exposure, and after therapy. OXTR exon III methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. RESULTS: Relative OXTR hypermethylation was observed in OCD patients compared to healthy controls. In OCD, higher baseline OXTR methylation was found to predict impaired treatment response at both categorical (responders vs. nonresponders) and dimensional (relative Y-BOCS reduction) levels, whereas lower baseline methylation was related to treatment response and greater symptom improvements. Analysis of Y-BOCS subdimensions revealed that the association between OXTR hypermethylation with impaired treatment response applied especially to symptoms related to obsessions, but not compulsions. CONCLUSIONS: OXTR hypermethylation may constitute a predictive marker of impaired treatment response in OCD and thus carries great potential for future personalized treatment efforts in OCD.

Monoamine Oxidase A Hypomethylation in Obsessive-Compulsive Disorder: Reversibility By Successful Psychotherapy?

BACKGROUND: Epigenetic markers such as DNA methylation of the monoamine oxidase A (MAOA) gene have previously been shown to be altered in anxiety- and stress-related disorders and to constitute a potential mechanism of action of psychotherapeutic interventions such as cognitive behavioral therapy in these disorders. The present study for the first time, to our knowledge, investigated MAOA methylation in patients with obsessive-compulsive disorder applying a longitudinal psychotherapy-epigenetic approach. METHODS: The present sample comprised 14 unmedicated female patients with primary obsessive-compulsive disorder and 14 age- and sex-matched healthy controls. MAOA promoter methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from whole blood before and after an 8- to 10-week semi-standardized, obsessive-compulsive disorder-specific cognitive behavioral therapy. Clinical response was assessed by means of the Yale-Brown Obsessive Compulsive Scale. RESULTS: Significantly lower MAOA promoter methylation was discerned in obsessive-compulsive disorder patients relative to healthy controls. Data were available for 12 patients with obsessive-compulsive disorder and 14 controls. Furthermore, following cognitive behavioral therapy, clinical improvement, i.e., decreases in obsessive-compulsive disorder symptoms as indicated by lower scores on the Yale-Brown Obsessive Compulsive Scale was found to be significantly correlated with increases in MAOA methylation levels in patients (data available for n = 7). CONCLUSIONS: The present pilot data suggest MAOA hypomethylation as a potential risk marker of obsessive-compulsive disorder and an increase in MAOA methylation levels as a possible mechanistic correlate of response to cognitive behavioral therapy in obsessive-compulsive disorder.

Structural alterations in patients with obsessive-compulsive disorder: a surface-based analysis of cortical volume, surface area and thickness.

BACKGROUND: Mounting evidence indicates the presence of structural brain alterations in individuals with obsessive-compulsive disorder (OCD). Findings are, however, rather heterogeneous, which may be partly because of differences in methodological approaches or clinical sample characteristics. The aim of the present study was to analyze the whole brain cortical volume, surface area and thickness in a large sample of patients with OCD compared with age- and sex-matched healthy controls. METHODS: We conducted whole brain surface-based analyses of grey matter measures using the automated FreeSurfer software in patients with OCD and matched controls. Group analyses were performed and corrected for multiple testing using Monte Carlo simulations (p < 0.05). Altered brain regions and their average morphological values were associated to symptom severity and type (Yale-Brown Obsessive Compulsive Scale scores). RESULTS: We included 75 patients and 75 controls in our analyses. Patients with OCD showed decreases in both volume and surface area compared with healthy controls in inferior-superior parieto-occipital regions. In addition, the precuneus, posterior cingulate areas, middle frontal and orbitofrontal areas, and middle inferior temporal areas extending to the fusiform gyrus were characterized by a reduced surface area only. There were no differences in grey matter thickness between the groups. LIMITATIONS: The presence of comorbidities, medication usage and the multisymptomatic feature of OCD could have influenced our results to a certain degree. CONCLUSION: Our results suggest decreased grey matter volume and surface area in several key regions in patients with OCD. Parietal regions showed reductions in both volume and surface area, which underlines the potential relevance of these regions for the pathophysiology of the disorder.

A retrospective classification of diagnoses in terms of DSM-5 for patients included in randomized controlled trials of Ginkgo biloba extract EGb 761(®).

When the early trials of Ginkgo biloba extract EGb 761(®) were conducted, different terms were used to denote ageing-associated neurocognitive disorders. With the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), a taxonomy covering dementia and pre-dementia stages of such disorders became available. DSM-5 diagnostic criteria for neurocognitive disorders (NCDs) were applied to patients with any type of ageing-associated cognitive impairment, including dementia, enrolled in randomized controlled clinical trials of EGb 761(®), taking into account the reported inclusion and exclusion criteria and patient characteristics at baseline. For 23 of 31 trials (74 %), the inclusion diagnoses could be classified as NCD in accordance with DSM-5. Thirteen trials enrolled patients with major NCD, four trials enrolled patients with mild NCD and six trials enrolled patients with NCD, who could not be classified unambiguously as having mild or major NCD. Although various terms were formerly used for neurocognitive disorders, the patients enrolled in the majority of clinical trials with EGb 761(®) could be classified retrospectively using modern DSM-5 diagnostic criteria.

Epigenome-wide DNA methylation in obsessive-compulsive disorder.

In adult patients with obsessive-compulsive disorder (OCD), altered DNA methylation has been discerned in several candidate genes, while DNA methylation on an epigenome-wide level has been investigated in only one Chinese study so far. Here, an epigenome-wide association study (EWAS) was performed in a sample of 76 OCD patients of European ancestry (37 women, age ± SD: 33.51 ± 10.92 years) and 76 sex- and age-matched healthy controls for the first time using the Illumina MethylationEPIC BeadChip. After quality control, nine epigenome-wide significant quantitative trait methylation sites (QTMs) and 21 suggestive hits were discerned in the final sample of 68 patients and 68 controls. The top hit (cg24159721) and four other significant QTMs (cg11894324, cg01070250, cg11330075, cg15174812) map to the region of the microRNA 12136 gene (MIR12136). Two additional significant CpG sites (cg05740793, cg20450977) are located in the flanking region of the MT-RNR2 (humanin) like 8 gene (MT-RNRL8), while two further QTMs (cg16267121, cg15890734) map to the regions of the MT-RNR2 (humanin) like 3 (MT-RNRL3) and MT-RNR2 (humanin) like 2 (MT-RNRL2) genes. Provided replication of the present findings in larger samples, the identified QTMs might provide more biological insight into the pathogenesis of OCD and thereby could in the future serve as peripheral epigenetic markers of OCD risk with the potential to inform targeted preventive and therapeutic efforts.

[Obsessive-compulsive disorder--clinical picture, diagnosis, and therapy]. / Die Zwangsstörung--Krankheitsbild, Diagnostik und Therapie.

This article reviews the present state of knowledge concerning obsessive-compulsive disorder (OCD) with respect to its classification, epidemiology, pathogenesis, and therapy. Epidemiological evidence has indicated that OCD may be one of the most prevalent and disabling psychiatric disorders. There is also a high comorbidity with depression and anxiety disorders. OCD is characterized by repetitive, intrusive thoughts and images, and/or by repetitive, ritualistic physical or mental acts performed to reduce the attended anxiety. OCD is relatively common, affecting 1-3% of both adult and paediatric samples. OCD is clinically a heterogeneous condition in that two different patients with clear OCD can display completely distinct symptom patterns. Furthermore, neurobiological and psychological models concerning OCD as well as the present state of therapy are presented in detail.

Serotonin transporter gene promoter hypomethylation in obsessive-compulsive disorder - Predictor of impaired response to exposure treatment?

Treatment resistance is common in obsessive-compulsive disorder (OCD) and associated with a significant burden for the individual patient. Accordingly, the identification of biomarkers as early predictors of the clinical response has become a central goal in the search for more efficacious and personalized treatments. Epigenetic mechanisms such as DNA methylation of the serotonin transporter gene (SLC6A4) have been suggested to predict therapy outcome in mental disorders closely related to OCD, but have not yet been investigated as such in OCD. The present therapy-epigenetic study therefore sought to address the potential role of SLC6A4 promoter methylation in the prediction of treatment response for the first time in OCD. Overall, 112 patients with primary OCD were investigated over the course of 8-10-week OCD-specific, cognitive behavioral therapy (CBT) comprising exposure and response prevention/management (phase I) and in vivo exposure exercises ('flooding', phase II). OCD symptoms were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline as well as before and after the in vivo exposure phase. SLC6A4 promoter methylation at baseline was analyzed via pyrosequencing of sodium bisulfite-treated DNA extracted from blood cells. Lower baseline SLC6A4 promoter methylation predicted impaired treatment response (defined as reduction in Y-BOCS scores) in phase II (but not phase I) of CBT (ß = -0.359, p = .002). SLC6A4 methylation may thus constitute a potential early biomarker predicting biologically mediated clinical changes elicited specifically by exposure treatment. These results carry promise for clinical application and in the future could aid in early treatment modification and personalized treatment efforts.

On the Relationship of Interoceptive Accuracy and Attention: A Controlled Study With Depressed Inpatients and a Healthy Cohort.

OBJECTIVE: Previous research has shown reduced interoceptive accuracy (IAcc) in depression. Attention deficit represents a key symptom of depression. Moreover, IAcc is positively correlated with attention. There is no study that investigates the effect of depression on IAcc and attention. The aim of this study is to examine the mediating effect of IAcc on depression and attention. METHODS: Thirty-six depressed patients from the Psychosomatic Clinic in Windach were matched with 36 healthy controls according to age and sex and were assessed at Ulm University. All participants completed the Beck Depression Inventory-II, the heartbeat perception task to examine IAcc, and the d2 test assessing selective attention. RESULTS: Depressed patients showed attention deficits-both for general visual attention and IAcc-compared to healthy controls. The mediation analyses revealed that the relationship between depression and attention is not mediated via IAcc. Furthermore, depression predicts IAcc and attention, but these effects are direct and largely unaffected by the respective other variable. DISCUSSION: The results of the present study highlight both interoceptive as well as attention deficits in depressed patients. No clear mediation between these variables could be shown in this study. More elaborative research is needed to clarify whether different approaches to improve IAcc are effective for these deficits in depressed patients and could therefore be of importance as an additional aspect of therapy in depression.

Predicting therapy outcome in patients with early and late obsessive-compulsive disorder (EOCD and LOCD).

BACKGROUND: Increasing attention has been given to subtyping OCD with respect to different clinical profiles, response to drug treatments, comorbidity and age of onset. There are a number of studies looking at predictors of treatment outcome in OCD, but so far not for OCD subtypes. METHOD: Prediction of outcome after cognitive-behavioural therapy was evaluated in 63 inpatients with early obsessive-compulsive disorder (EOCD < or = 12 years of age) and 191 patients with late obsessive-compulsive disorder (LOCD > 15 years of age). RESULTS: For EOCD patients factors predicting a good outcome included high motivation and high initial Y-BOCS scores. Factors associated with a bad outcome were higher age at assessment, a longer duration of psychiatric inpatient treatment before assessment and a low level of social functioning (BSS). For LOCD patients living in a stable relationship, high motivation and completing treatment predicted a favourable therapy outcome, while a low level of psychological functioning (BSS) and a longer duration of inpatient psychiatric treatment before assessment were associated with an undesirable therapy outcome. CONCLUSIONS: Subtyping OCD patients according to age of onset seems to be a promising avenue towards improving and developing more specified treatment programs.

[The effectiveness of psychosomatic inpatient treatment - results of a multicenter follow-up study]. / Effektivität stationärer psychosomatischer Krankenhausbehandlung - Ergebnisse einer multizentrischen Katamnesestudie.

OBJECTIVES: This multicenter follow-up study examines the effectiveness of psychosomatic inpatient treatment under the conditions of routine practice. METHODS: We chose a naturalistic design with one pre- and two postmeasurements: admission, discharge, and 1-year follow-up with a follow-up sample of 935 patients from five psychosomatic hospitals.We assessed the effectiveness of inpatient psychosomatic treatments with the Global Severity Index (GSI) of the SCL-90-R at admission (M = 1.20, SD = 0.68), discharge (M = 0.67, SD = 0.58), and 1-year follow-up (M = 0.83, SD = 0.68) as well as with the Veränderungsfragebogen des Erlebens und Verhaltens (VEV-K) at discharge (M = 125.42, SD = 27.27) and follow-up (M = 115.50, SD = 31.16). RESULTS: Significant improvements were shown in the GSI from admission to discharge (F = 802.70, df = 1, p

Interoceptive deficits in patients with obsessive-compulsive disorder in the time course of cognitive-behavioral therapy.

Interoception is impaired in different psychiatric disorders and is also associated with emotions. Only one study could show a higher interoceptive accuracy (IAcc) in patients with obsessive-compulsive disorder (OCD). Based on the predictive coding system we assume contrary results, indicating a decreased IAcc in patients with OCD. So far, there is no study investigating the effect of cognitive-behavioral therapy on IAcc in patients with OCD. Therefore, we hypothesize that patients with OCD improve their IAcc during the time course of therapy compared to healthy controls. Twenty-six patients with OCD from the Psychosomatic Clinic in Windach were examined in the time course of cognitive-behavioral therapy. They were compared to 26 matched healthy controls. IAcc via the heartbeat perception task as well as questionnaire data (OCD-, depression- and anxiety symptoms) were assessed. Results showed that IAcc, OCD-, depression- and anxiety symptoms were attenuated in patients with OCD. Patients recovered in the time course of therapy regarding OCD-, depression- and anxiety symptoms. Interoceptive deficits did not change in the time course of cognitive-behavioral therapy. We demonstrated that IAcc is affected in patients with OCD and this deficit does not change during the time course of a standardized therapy. Future studies should investigate, whether an inaccuracy in perceiving one's bodily signals constitutes a risk factor for relapse. Further, it could be examined if IAcc can be increased via self- and body focus interventions in patients with OCD.

Electrophysiological evidence for cortical abnormalities in obsessive-compulsive disorder - a replication study using auditory event-related P300 subcomponents.

Neuroimaging studies in recent years suggest that cortical hyperactivity associated with more aroused cognitive processes and overfocussed attention is involved in the pathogenesis of obsessive-compulsive disorder (OCD), which was electrophysiologically supported by an own pilot-study in a small sample of stabilized OCD patients. To replicate this first finding, the hypothesis of cortical hyperactivity was studied by measuring auditory event-related P300 subcomponents, especially the amplitude of the P3a and P3b subcomponent, in a large sample of acutely ill and unmedicated patients with OCD. The P300 of 63 patients with OCD (30 males, 33 females, 33.7+/-10.2 years old; 25.4+/-5.4 points at Yale-Brown-Obsessive-Compulsive-Scale (Y-BOCS)) was separated with dipole source analysis (BESA) into their subcomponents P3a and P3b, and compared to the P300 subcomponents of 63 gender and age matched healthy controls. No difference in the amplitude of P3a was found, but OCD patients had significantly larger amplitudes of P3b than the healthy controls, which replicates the results of the pilot study. Once again, our findings point to a hyperactivated cortical state also of temporo-parietal and hippocampal regions in OCD.

[Development of the "ICD-10-Symptom-Rating"(ISR) questionnaire]. / Entwicklung des Fragebogens "ICD-10-Symptom-Rating" (ISR).

OBJECTIVES: Construction of the newly developed "ICD-10 Symptom Rating" (ISR) is presented together with some statistical data. This questionnaire is founded on the well-known ICD-10, according to which symptoms are relevant for assessing psychological disorders. The ISR aims at a comprehensive evaluation of the severity of psychological disorders. The ISR 2.0 has 29 items and six syndrome scales: Depression, Anxiety, Obsessive/Compulsive, Somatoform, Eating Disorders, and the Supplementary Scale, which covers a variety of syndromes, as well as a total score. METHODS AND RESULTS: In a first cross-validation with 108 patients, some rather high correlations were found between the SCL-90-R and the ISR. They ranged from r = 0.78 to 0.37 for the individual syndrome scales, and amounted to r = 0.78 for the GSI versus the total score.

Mild cognitive impairment.

Mild cognitive impairment is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. Prevalence in population-based epidemiological studies ranges from 3% to 19% in adults older than 65 years. Some people with mild cognitive impairment seem to remain stable or return to normal over time, but more than half progress to dementia within 5 years. Mild cognitive impairment can thus be regarded as a risk state for dementia, and its identification could lead to secondary prevention by controlling risk factors such as systolic hypertension. The amnestic subtype of mild cognitive impairment has a high risk of progression to Alzheimer's disease, and it could constitute a prodromal stage of this disorder. Other definitions and subtypes of mild cognitive impairment need to be studied as potential prodromes of Alzheimer's disease and other types of dementia.

Measuring cognitive change in older adults: reliable change indices for the SIDAM.

BACKGROUND: In clinical settings, neuropsychological tests and screening instruments are often used to measure cognitive change over time. However, the interpretation of changes in test scores is often difficult. For most instruments there is no information how much change occurs normally in cognitively healthy individuals. AIM: To examine what is a reliable change for a widely used screening instrument for cognitive impairment and dementia. METHODS: A Sample of 119 cognitively normal elderly individuals aged 75 and over participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants have been tested six times at 1.5 year intervals with the test part of the SIDAM over a mean period of 7.1 years. Reliable change indices (RCI) were computed for a common confidence interval (90%). It is demonstrated how to compute RCI for individual patients. RESULTS: In repeated assessments with 1.5 year intervals, a change in SIDAM score of at least 4 to 7 points (dependent on which of the six assessments were compared) indicates a reliable change at the 90% confidence level. Smaller changes can be interpreted only with high uncertainty. CONCLUSION: The interpretation of changes in test scores in older adults should account for potential practice effect, normal decline and regression to the mean.

Functional and structural connectivity of the amygdala in obsessive-compulsive disorder.

BACKGROUND: The amygdala is known to be involved in anxiety processing, but its role in the psychopathology of obsessive-compulsive disorder (OCD) is still unclear. AIMS: In this MRI study we investigated potential alterations in structural and functional connectivity of the amygdala in 42 adult patients with OCD and 37 healthy subjects. METHOD: Psychophysiological interaction analysis was used to explore amygdala functional connectivity during a negative affective task. Probabilistic tractography was then employed to study structural connectivity and integrity of underlying white matter fiber tracts. RESULTS: Compared to controls, OCD patients showed a significantly increased functional connectivity of the left amygdala with mostly parieto-occipital regions during task. No structural connectivity differences could be found between the groups. In addition, only patients showed a significant association between functional and structural connectivity of these regions. Moreover, symptom severity was negatively associated with structural integrity of the underlying white matter tracts. CONCLUSIONS: Present results emphasize the relevance of the amygdala for OCD and may reflect that neuronal alterations in structural connectivity could be associated with functional connectivity alterations in broader networks.

Symptom-specific EEG power correlations in patients with obsessive-compulsive disorder.

Neurophysiological studies in patients with obsessive-compulsive disorder (OCD) consistently revealed frontal alterations of cortical activity but otherwise showed inhomogeneous results, conceivably due to variable subgroups with diverse pathomechanisms involved. The aim of this study was to investigate quantitative electroencephalography (EEG) in patients with OCD as compared to healthy controls and to correlate neurophysiological data with clinical variables. EEGs were digitally recorded from 18 unmedicated patients (8 male, mean age 32.4+/-11.8 years, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 15.3+/-7.9) and 18 matched healthy controls, and analysed quantitatively. The mean frequency of EEG background activity and absolute power in delta, theta, alpha and beta frequency bands were calculated. Mean frequency of background activity was significantly lower in patients as compared to controls (-1.44/s, p<0.01), predominantly for the frontal electrode positions. Power spectra revealed increased delta- and decreased alpha-/beta-power in the group of patients (p<0.05, patients vs. controls). Correlation analyses showed significant positive correlations of EEG-power with the Y-BOCS sub-scores "obsessions", and negative correlations with the sub-scores "compulsions" (Spearman's correlations, r(s)=+0.48 to +0.70, and -0.47 to -0.6, respectively, p<0.05). The data provide evidence of a dysfunction of frontal cortical activity in patients with OCD. The opposite correlations of neurophysiological data and clinical features, i.e. obsessions and compulsions, are suggestive of pathophysiological differences based on the presence of the respective cardinal symptoms of OCD.

Interoceptive Processes in Anorexia Nervosa in the Time Course of Cognitive-Behavioral Therapy: A Pilot Study.

OBJECTIVE: Previous studies report reduced interoceptive abilities in anorexia nervosa (AN) using various methods. Recent research suggests that different levels of interoceptive processes aiming at different subdomains of interoceptive abilities must be further distinguished as these levels can be differentially affected. Two important levels refer to interoceptive accuracy (IA) derived from objective performance tasks such as the heartbeat detection task and interoceptive sensibility (IS) as assessed by self-report. There is a lack of studies investigating both IA and IS in AN and examining them in the time course of therapy. The aim of this pilot study was to evaluate the different interoceptive processes - especially IA and IS - in the time course of therapy. METHODS: Fifteen patients with AN (restricting type) from the Psychosomatic Clinic in Windach were investigated three times (T1, T2, T3) during a standardized cognitive-behavioral therapy and compared with 15 matched healthy controls assessed at Ulm University in a comparable design. All participants performed the heartbeat detection task examining IA and completed standard psychological assessments including an assessment of IS. RESULTS: Patients with AN showed a significantly decreased weight, higher levels of depression, and both reduced IA and IS compared to healthy controls at T1. Following therapy, patients recovered in terms of weight and depression symptomatology. A descriptive trend for recovering from IA and IS was observed. DISCUSSION: Our findings suggest that interoceptive deficits are present in recovered patients. Therefore, further investigations are needed with more patients, differentiating between relapsed and recovered patients, and more specific training methods to improve interoceptive processes.

Atypical Self-Focus Effect on Interoceptive Accuracy in Anorexia Nervosa.

Background: Interoceptive abilities are known to be affected in anorexia nervosa (AN). Previous studies could show that private self-focus can enhance interoceptive accuracy (IAcc) in healthy participants. As body dissatisfaction is high in AN, confrontation with bodily features such as the own face might have a directly opposed effect in AN. Whether patients with AN can benefit from self-focus in their IAcc and whether this pattern changes over the time-course of cognitive behavioral therapy was investigated in this study. Methods: Fifteen patients with AN from the Psychosomatic Clinic in Windach were assessed three times in the time course of a standardized cognitive-behavioral therapy. They were compared to 15 controls, recruited from Ulm University and tested in a comparable setting. Both groups performed the heartbeat perception task assessing IAcc under two conditions either enhancing ("Self") or decreasing ("Other") self-focused attention. Furthermore, body dissatisfaction was assessed by a subscale of the Eating Disorder (ED) Inventory 2. Results: Patients with AN scored higher in IAcc when watching others' faces as compared to one's own face while performing the heartbeat perception task. The opposite pattern was observed in controls. IAcc remained reduced in AN as compared to controls in the time-course of cognitive-behavioral therapy, while body-dissatisfaction improved in AN. High body dissatisfaction was related to poorer IAcc in the "Self" condition. Conclusions: Our findings suggest that using self-focused attention reduces IAcc in AN while the opposite pattern was observed in controls. Confronting anorexic patients with bodily features might increase body-related avoidance and therefore decrease IAcc. The current study introduces a new perspective concerning the role of interoceptive processes in AN and generates further questions regarding the therapeutic utility of methods targeting self-focus in the treatment of AN.

Implicit sequence learning in obsessive-compulsive disorder: further support for the fronto-striatal dysfunction model.

BACKGROUND: Obsessive-compulsive disorder (OCD) is conceived as a disease that implicates dysfunctions in fronto-striatal brain systems. According to this model, performance deficits observed in patients with lesions in these brain areas are hypothesized to be present also in OCD patients. Implicit procedural learning, which refers to the acquisition of motor or nonmotor skills by practice, is one candidate function to test this prediction. METHODS: The serial reaction time task was used to assess implicit sequence learning of 33 patients with a diagnosis of OCD and 27 healthy control participants. In addition, explicit (i.e., conscious) knowledge of the sequence was determined. A subgroup of 24 patients was reassessed after intensive cognitive-behavioral psychotherapy. RESULTS: Implicit sequence learning was significantly reduced in the OCD group by 41%, while explicit learning and verbal abilities were unaffected. The deficit remained stable across time, although symptoms remitted substantially. Depressive symptoms did not account for the finding. Partial explicit knowledge of the sequence was not a predictor of the amount of implicit learning. CONCLUSIONS: Reduced implicit learning appears to be a dissociable trait of OCD patients. The results confirm previous findings and add supportive evidence for the fronto-striatal dysfunction model of OCD.