Neuroimaging studies of obsessive compulsive disorder.

In the last 5 years, there has been an explosion of neuroimaging studies of obsessive compulsive disorder. This work is now beginning to suggest dysfunctional brain regions and circuits that may mediate some of the symptoms of this classic neuropsychiatric illness.     

Neuroimaging communality between schizophrenia and obsessive compulsive disorder: a putative basis for schizo-obsessive disorder?

Four major brain regions have been repeatedly implicated in the pathophysiology of obsessive compulsive disorder (OCD) in in vivo neuroimaging studies: the caudate nucleus, the orbitofrontal cortex, the anterior cingulate gyrus and the mediodorsal thalamic nucleus. The present review describes the neuroimaging studies on schizophrenia, pertaining to these brain regions. Our working hypothesis is that such common brain regions, if dysfunctional in schizophrenic patients, would be candidates for a neural network subserving the newly emerging syndrome of schizo-obsessive disorder. Findings, though, are controversial. We conclude that further studies, aimed at specific monitoring of these brain regions, in patients suffering from the schizo-obsessive syndrome are warranted.     

Prefrontal tDCS and sertraline in obsessive compulsive disorder: a case report and review of the literature

Obsessive-compulsive (OC) disorder is a disabling disorder resulting in tremendous individual and social burden. It has a large overlap with depression and anxiety disorders and shows treatment resistance in a relevant proportion of patients. Since a couple of years, different noninvasive brain stimulation methods have been investigated to improve OC symptoms. The application of transcranial direct current stimulation (tDCS) has shown inconsistent results which can probably be attributed to a lack in randomized controlled trials with adequate sample size. Anodal stimulation of pre-supplementary motor areas has shown promising results, and there is also sparse data on orbitofrontal and prefrontal stimulation. Here, we provide the first report on a patient with treatment-refractory OC disorder treated with sertraline and an enhanced prefrontal tDCS protocol (twice per day, 10 days) with a classic left-anodal/right cathodal montage, experiencing a 22% reduction of OC symptoms as well as reduction in depression (?10%) and anxiety symptoms (?21%). Due to multifactorial origin of OC disorder and the variety of brain circuits involved, there are probably multiple approaches for brain stimulation regarding site, polarity, and frequency to be assessed in future studies.     

Increased orbital frontal gray matter volume after cognitive behavioural therapy in paediatric obsessive compulsive disorder

Abstract

Objectives. Identify differences in regional brain volume between medication-free pediatric OCD patients and controls and examine changes after cognitive behavioural therapy. Methods. We assessed 29 medication-free paediatric OCD patients (Age: M =?13.78 years; SD =?2.58; range 8.2–19.0) and 29 controls, matched on age and gender, with T1-weighted MR scans in a repeated measures, pre-post treatment design. Voxel based morphometry (VBM) following diffeomorphic anatomical registration through exponential lie algebra (DARTEL) was used to test voxel-wise for the effects of diagnosis and treatment on regional gray matter (GM) and white matter (WM) volumes. Results. After cognitive behavioural therapy, orbitofrontal GM and capsula externa WM increased in paediatric OCD relative to controls. In patients, changes in symptom severity (delta CY-BOCS) correlated positively with GM volume in the orbitofrontal cortex after treatment. Furthermore, before treatment, paediatric OCD patients, compared to the controls, showed larger GM volume in left frontal pole and left parietal cortex and larger WM volume in cingulum and corpus callosum. Conclusions. Our findings underscore the involvement of the ventral frontal-striatal circuit in paediatric OCD and the plasticity of this circuit in response to the modulatory effects of CBT. The possible relation to brain development is discussed.     

Current animal models of obsessive compulsive disorder: a critical review

During the last 30 years there have been many attempts to develop animal models of obsessive compulsive disorder (OCD), in the hope that they may provide a route for furthering our understanding and treatment of this disorder. The present paper reviews current genetic, pharmacological and behavioral animal models of OCD, and evaluates their face validity (derived from phenomenological similarity between the behavior in the animal model and the specific symptoms of the human condition), predictive validity (derived from similarity in response to treatment) and construct validity (derived from similarity in the underlying mechanisms--physiological or psychological).     

Single photon emission computerized tomography in obsessive compulsive disorder: a preliminary study.

Patterns of cerebral perfusion in patients with obsessive compulsive disorder were evaluated using single photon emission computerized tomography. Eleven patients, who satisfied the DSM-III-R criteria and Research Diagnostic Criteria for the disorder, were evaluated using the distribution of 99m-Tc-HMPAO as a radiotracer. The Yale-Brown Obsessive Compulsive Scale was administered to each patient to assess the severity of their symptoms. The images obtained were evaluated qualitatively and semi-quantitatively by a physician in nuclear medicine who was blind to the patients' diagnoses. Eight of the 11 patients demonstrated asymmetric perfusion of the basal ganglia; the left side showed impaired perfusion in six patients.     

Brain activation in paediatric obsessive compulsive disorder during tasks of inhibitory control

BACKGROUND: Obsessive-compulsive disorder (OCD) may be related to a dysfunction in frontostriatal pathways mediating inhibitory control. However, no functional magnetic resonance imaging (fMRI) study has tested this in children. AIMS: To test whether adolescents with OCD in partial remission would show abnormal frontostriatal brain activation during tasks of inhibition. METHOD: Event-related fMRI was used to compare brain activation in 10 adolescent boys with OCD with that of 9 matched controls during three different tasks of inhibitory control. RESULTS: During a 'stop' task, participants with OCD showed reduced activation in right orbitofrontal cortex, thalamus and basal ganglia; inhibition failure elicited mesial frontal underactivation. Task switching and interference inhibition were associated with attenuated activation in frontal, temporoparietal and cerebellar regions. CONCLUSIONS: These preliminary findings support the hypothesis that paediatric OCD is characterised by a dysregulation of frontostriatothalamic brain regions necessary for motor inhibition, and also demonstrate dysfunction of temporoparietal and frontocerebellar attention networks during more cognitive forms of inhibition.     

Pregnancy-induced obsessive compulsive disorder: a case report

Pregnancy is a well-recognised risk factor in precipitating obsessive-compulsive disorder. We present and discuss a case with the onset of obsessive-compulsive disorder in the fourth month of gestation, which fully recovered two weeks after delivery. The phenomenology of the observed disorder was similar to earlier reports of obsessive-compulsive disorder in pregnancy, i.e. the obsessions and compulsions were predominantly related to the concern of contaminating the foetus resulting in washing compulsions. Despite the initial success with anti-obsessional drugs, the patient stopped the medication in the last month of gestation. Nevertheless, she fully recovered two weeks after the delivery without any psychiatric intervention. There were no obsessive-compulsive symptoms at one-year follow up. The possible mechanisms involved in the aetiology of this case, and future research directions in understanding the role of pregnancy in OCD are discussed.     

Depressive and anxiety disorder comorbidity in obsessive compulsive disorder

BACKGROUND: Depressive and other anxiety disorders are commonly found to coexist with obsessive compulsive disorder (OCD). Although western studies have looked at this issue, there are no reports from India investigating anxiety and depressive comorbidity in adult OCD. METHODS: Between January and December 2001, charts of 218 OCD patients seen in the OCD clinic at the National Institute of Mental Health and Neurosciences, Bangalore, were evaluated using the OPCRIT criteria for ICD-10 for the presence of comorbid depressive and anxiety disorders. RESULTS: There were 146 males and 72 females; their mean age at OCD onset was 21.32 +/- 0.64 years. Thirty-six (16.5%) patients had depressive episodes, 12 (5.5%) dysthymia and 15 (6.9%) any anxiety disorder. No significant difference in terms of age, sex, marital status or age at onset was found between the OCD patients with and without comorbid anxiety disorder, major depression or dysthymia, except that female OCD patients were more likely than males to have comorbid major depressive disorder. CONCLUSIONS: The results of our study are in keeping with previous data from other parts of the world, though the actual rates of comorbidity in our sample appear to be much lower. It remains to be seen whether the differences in rates are a result of methodological issues or different characteristics of sample populations. Further long-term, prospective, methodologically sound studies investigating the comorbidity of depressive and other anxiety disorders in OCD patients are needed to clarify this issue.     

Insight in obsessive compulsive disorder and body dysmorphic disorder

Similarities between obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) have been described in terms of clinical presentation, comorbidity rates, treatment response profiles, and other features. This is the first study to compare insight in OCD and BDD measuring global insight and numerous components of insight. We compared insight in 64 adult outpatients with DSM-IV OCD and 85 adult outpatients with DSM-IV BDD using a reliable and valid measure (the Brown Assessment of Beliefs Scale [BABS]). BDD patients had significantly poorer global insight than OCD patients. BDD patients also had significantly poorer insight on the following components of insight: conviction that the belief is accurate, perception of other's views of the belief, explanation for differing views, willingness to consider that the belief is wrong, and recognition that the belief has a psychiatric/psychological cause. Poorer insight was significantly positively correlated with more severe symptoms of the disorder only in the BDD group.     

Toward a new nosology of obsessive compulsive disorder

Obsessive compulsive disorder (OCD) is receiving increasing attention in the clinical research literature. This review briefly summarizes data concerning diagnosis, phenomenology, and epidemiology of OCD and examines other disorders that closely resemble OCD. In addition, the nosological and treatment implications of these data are discussed. We find that OCD is characterized by a focal anxiety point(s) reflected in obsessions and by behavioral or cognitive compulsions. The appearance of these characteristics in other disorders suggests some relation between them and, consequently, the treatment of these disorders may be enhanced by conceptualizing them as OCD "variants".     

Dysfunctional beliefs in group and individual cognitive behavioral therapy for obsessive compulsive disorder

The primary aim of the study was to investigate dysfunctional beliefs in the form of inflated responsibility (IR) and thought action fusion (TAF) as predictive and mediating variables in individual (n = 33) and group (n = 37) cognitive behavioral therapy (CBT) for obsessive compulsive disorder (OCD). IR and TAF declined significantly during CBT, and the decline was positively associated with change in OCD symptoms. However, when controlling for change in depressive symptoms, only change in IR remained significantly associated with OCD symptom change. The moral subtype of TAF predicted poorer treatment outcome, but only in group CBT. Both treatments produced a similar amount of change in the dysfunctional beliefs. The results provide some, preliminary evidence that IR, but not TAF, may be specifically involved in the change mechanisms of both individual and group CBT for OCD, although the design of the study with pre- and post-therapy measurements only does not allow for a causal mediator analysis.     

Exploration of obsessive compulsive phenomena: a preliminary investigation.

Different dimensions of obsessions and compulsions were explored in 103 obsessions and 60 compulsions recorded from 32 subjects who received a primary diagnosis of obsessive compulsive disorder. Intrusiveness and repetitiveness formed relatively discrete dimensions, while resistance, distress, irrationality, interference and ease of dismissal tended to be associated within themselves. An anxiety-provoking effect was an additional dimension observed among compulsions.     

Dysregulation of neurosteroids in obsessive compulsive disorder

Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD.     

Dopamine function in obsessive compulsive disorder: cortisol response to acute apomorphine stimulation

Central dopaminergic dysfunction has been suggested to be involved in the pathogenesis of obsessive compulsive disorder (OCD). In 15 patients with OCD and in 15 age-sex matched controls we evaluated the dopamine (DA) function by measuring the cortisol (CORT) responses to stimulation with the DA agonist apomorphine (APO). The CORT response to acute saline administration was also measured, to exclude the existence of a pathology of the circadian secretion of the hormone which could obscure the significance of the CORT response to APO stimulation. Basal levels of CORT were the same in patients and controls, but the values after saline administration were significantly higher in patients than in controls. APO stimulation-induced CORT rises were significantly higher in patients than in controls, but when the data after APO were corrected for those after saline, there were no significant difference between the two groups of subjects. Our data suggest that there are no alterations of the central dopaminergic function connected with the regulation of the hypothalamo-pituitary-adrenal axis in OCD.     

Predictors of course in obsessive compulsive disorder

Systematic studies of course of illness in obsessive compulsive disorder (OCD) using standardized diagnostic criteria are relatively rare. In the present study, 100 patients diagnosed with OCD were prospectively followed for up to 5 years. Other comorbid conditions included anxiety disorders (76%), major depressive disorder (33%), and at least one personality disorder (33%), mainly in the anxious cluster. Approximately 20% of patients had full remission and 50% had partial remission during follow-up. Significant predictors of partial remission included being married and having lower global severity scores at intake; the presence of major depression was marginally predictive of poorer course. Adequate serotonergic medication was associated with worse course, but findings are likely spurious. Only marital status and global severity were retained as predictors in a final regression model. Findings are discussed with regard to sample characteristics and similarity to other reports on predictors of course and of treatment outcome.     

Sensitivity of self-beliefs in obsessive compulsive disorder

Aspects of self-concept have been implicated in recent cognitive theories of obsessive compulsive disorder (OCD). It has been proposed that OCD is associated with perceptions of incompetence in self-domains considered important by the individual. A previous study in nonclinical individuals found that such "sensitivity of self" in the areas of job competence, morality and social acceptability was associated with elevated OCD symptoms and related beliefs. This study examined whether self-sensitivity is related to higher OCD symptoms and cognitions in individuals with OCD, and whether such self-sensitivity is specific to OCD versus other anxiety disorders. Clinical samples with OCD (N=30), other anxiety disorders (N=20) and a community control sample (N=32) participated in the study. It was found that in the OCD group, sensitivity in moral domains, but not job competence or social acceptability, was associated with higher levels of OCD symptoms and OCD-related beliefs. Sensitivity in the domains of morality and job competence was found in the OCD cohort, whereas individuals with other anxiety disorders did not show such sensitivity, suggesting some specificity of relationships to OCD. Implications for theory and therapy are discussed.     

Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder

Abstract

Objectives. The abnormal processing of emotional stimuli is common to a variety of psychiatric disorders. Specifically, patients with prominent anxiety symptoms generally overreact to emotional cues, which has been linked to increased amygdala activation. However, in OCD, enhanced responses are predominantly obtained using disease-specific stimuli and preferentially involve frontostriatal systems. Methods. We assessed 21 OCD patients and 21 healthy controls with fMRI during an emotional face-processing paradigm involving active response generation to test for alterations in both brain activation and task-induced functional connectivity of the frontal cortex, the amygdala and the fusiform face area. Results. OCD patients showed significantly greater activation of “face-processing” regions including the amygdala, fusiform gyrus and dorsolateral prefrontal cortex. The reciprocal connectivity between face-processing regions was enhanced in OCD. Importantly, we detected significant correlations between patients’ clinical symptom severity and both task-related region activation and network functional connectivity. Conclusions. The results suggest that OCD patients may show enhanced brain responsiveness during emotional face-processing when tasks involve active response generation. Our findings diverge from previously described alterations in anxiety disorders, as patients showed enhanced amygdala-prefrontal connectivity as opposed to negative reciprocal interaction. This pattern would appear to be disorder-specific and was significantly related to obsessive-compulsive symptom severity.