Femke de Geus

Dysfunctional Reward Circuitry in Obsessive-Compulsive Disorder

BACKGROUND Obsessive-compulsive disorder (OCD) is primarily conceived as an anxiety disorder but has features resembling addictive behavior. Patients with OCD may develop dependency upon compulsive behaviors because of the rewarding effects following reduction of obsession-induced anxiety. Reward processing is critically dependent on ventral striatal-orbitofrontal circuitry and brain imaging studies in OCD have consistently shown abnormal activation within this circuitry. This is the first functional imaging study to investigate explicitly reward circuitry in OCD. METHODS Brain activity during reward anticipation and receipt was compared between 18 OCD patients and 19 healthy control subjects, using a monetary incentive delay task and functional magnetic resonance imaging. Reward processing was compared between OCD patients with predominantly contamination fear and patients with predominantly high-risk assessment. RESULTS Obsessive-compulsive disorder patients showed attenuated reward anticipation activity in the nucleus accumbens compared with healthy control subjects. Reduced activity of the nucleus accumbens was more pronounced in OCD patients with contamination fear than in patients with high-risk assessment. Brain activity during reward receipt was similar between patients and control subjects. A hint toward more dysfunctional reward processing was found in treatment-resistant OCD patients who subsequently were successfully treated with deep brain stimulation of the nucleus accumbens. CONCLUSIONS Obsessive-compulsive disorder patients may be less able to make beneficial choices because of altered nucleus accumbens activation when anticipating rewards. This finding supports the conceptualization of OCD as a disorder of reward processing and behavioral addiction.

Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder

BACKGROUND Despite growing evidence for involvement of the dopaminergic system in obsessive-compulsive disorder (OCD), the functional anatomy of the dopaminergic system in the basal ganglia has been investigated sparsely. METHODS Dopamine D(2) receptor binding was assessed in 10 medication-free OCD patients and 10 healthy control subjects, matched for age, gender, and handedness. The binding potential was measured with single photon emission computerized tomography (SPECT) and infusion of the D(2) receptor radiotracer [(123)I] iodobenzamide. With magnetic resonance imaging as reference, regions of interest (caudate and putamen) were delineated for each hemisphere and coregistered with the corresponding SPECT scans. RESULTS Dopamine D(2) receptor binding in the left caudate nucleus was significantly lower in the patients with OCD than in healthy control subjects [F(1,18) = 7.0, p =.016]. In addition, an interhemispheric difference was observed in the patient sample. Both the D(2) receptor binding potential (df = 9, p =.012), and the volume (df = 9, p =.029) of the left caudate nucleus were statistically significantly reduced relative to the right caudate nucleus. CONCLUSIONS This study provides in vivo evidence for abnormalities in the binding potential of the dopamine D(2) receptor, which suggest the direct involvement of the dopaminergic system in the pathophysiology of OCD.

Axis I and II comorbidity in a large sample of patients with obsessive–compulsive disorder

BACKGROUND No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. OBJECTIVE To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD). METHOD 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. RESULTS Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. LIMITATIONS A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. CONCLUSION Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Use of factor analysis to detect potential phenotypes in obsessive-compulsive disorder.

This study aimed to identify symptom dimensions in obsessive-compulsive disorder (OCD) in order to reveal distinct clinical phenotypes. Factor analysis of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist on item level was performed on data from 335 outpatients with primary OCD. The relationship of demographic and clinical characteristics to the resulting factor scores was examined. A principal component analysis identified the following five consistent symptom dimensions: (1) contamination and cleaning, (2) aggressive, sexual and religious obsessions, (3) somatic obsessions and checking, (4) symmetry and counting/arranging compulsions and (5) high-risk assessment and checking. We observed significant differences in sex distribution, age of onset, Y-BOCS scores and familial prevalence of OCD in relation to the symptom dimensions. These findings provide further evidence for distinct clinical phenotypes in OCD.

Attention and cognition in patients with obsessive–compulsive disorder

Abstract  Although a dysfunctional prefrontal‐striatal system is presupposed in obsessive–compulsive disorder (OCD), this is not sustained by neuropsychological studies. The aim of this study was twofold: (i) to investigate the cognitive deficits in patients with OCD compared to matched healthy controls; and (ii) to relate cognitive performance to clinical characteristics in patients with OCD. In this study, 39 patients with primary OCD according to Diagnostic and Statistical Manual, fourth edition criteria were compared to 26 healthy control subjects on a battery measuring verbal memory and executive functioning. Patients with OCD showed slowed learning on the verbal memory task and made more errors on the Wisconsin Card Sorting Test. Errors were failures to maintain set, which were related to severity of OCD symptomatology. The results show that patients with OCD have cognitive deficits. The authors hypothesize that these deficits may be interpreted by attentional deficits caused by a dysfunctional anterior cingulate cortex.

Symptom dimensions in obsessive-compulsive disorder: Factor analysis on a clinician-rated scale and a self-report measure

Although obsessive-compulsive disorder (OCD) is regarded as a unitary nosological entity, it encompasses a rich variety of heterogeneous mental and behavioural phenomena. The identification of clinical subtypes within this broad concept has been a focus of attention in recent years. In the present study, we administered a clinician-rated scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with the Y-BOCS Symptom Checklist (Y-BOCS CL), as well as a self-report questionnaire, the Padua Inventory revised (PI-R), to 150 outpatients with OCD. A principal component analysis on the Y-BOCS CL, along with the PI-R, identified 6 consistent symptom clusters: (1) contamination obsessions and cleaning compulsions, (2) sexual/religious/somatic obsessions and checking, (3) high risk assessment and checking, (4) impulses and fear of loss of control, (5) need for symmetry and exactness, and ordering and counting compulsions, and finally (6) rumination. The Y-BOCS CL and PI-R showed great overlap and consistency regarding content and severity of the OCD symptoms. On inspection of items with identical content, only half of the items showed significant agreement. Both inventories have unique factors: rumination is represented solely in the PI-R, somatic obsessions and checking solely in the Y-BOCS CL. This means that the use of both clinician-administered and self-report measures is recommended, so that the entire spectrum of symptoms is represented.

A score for predicting response to pharmacotherapy in obsessive-compulsive disorder.

Although there have been many attempts to find predictors of therapeutic response to antidepressant treatment of obsessive–compulsive disorder (OCD), few reports have evaluated the joint predictive value of a number of clinical characteristics. This study aimed to identify clinical predictors of outcome in OCD, and to develop an easily applicable method to predict response to drug treatment. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week, double-blind, comparison trial with a selective serotonin reuptake inhibitor (paroxetine), and a serotonin-noradrenaline reuptake inhibitor (venlafaxine). The primary efficacy parameter was the Yale–Brown obsessive–compulsive scale (Y-BOCS) score, and response to treatment was prospectively defined as a ≥ 35% decrease from the beginning. A stepwise multivariate analysis was used to identify predictors. The absence of previous therapies, moderate baseline severity of obsessive–compulsive symptoms (Y-BOCS score < 23), and low Hamilton Depressive Rating Scale scores (6–15) were found to be prognostic determinants of good response to pharmacotherapy. The prognostic ability of the prediction model to discriminate between responders and non-responders was quantified as the area under the receiver operating/operator characteristic curve (ROC area), which was 0.71 (95% confidence interval 0.63–0.8), demonstrating a reasonable discriminatory power. This study is the first to present a model that can estimate by the use of prediction rules the probability of treatment response to antidepressants in patients with OCD.