Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity.

Cognitive-behavioral therapy (CBT) is effective for obsessive compulsive disorder (OCD); however, little is understood about its mechanisms related to brain network connectivity. We examined connectivity changes from resting-state functional magnetic resonance imaging data pre-to-post-CBT in 43 OCD participants, randomized to receive either 4 weeks of intensive CBT or 4 weeks waitlist followed by 4 weeks of CBT, and 24 healthy controls before and after 4 weeks of no treatment. Network-based-statistic analysis revealed large-magnitude increases in OCD connectivity in eight networks. Strongest increases involved connectivity between the cerebellum and caudate/putamen, and between the cerebellum and dorsolateral/ventrolateral prefrontal cortices. Connectivity increases were associated with increased resistance to compulsions. Mechanisms of CBT may involve enhanced cross-network integration, both within and outside of classical cortico-striatal-thalamo-cortical regions; those involving cerebellar to striatal and prefrontal regions may reflect acquisition of new non-compulsive goal-directed behaviors and thought patterns. Our findings have implications for identifying targets for enhancing treatment efficacy and monitoring treatment progress

Involvement of NMDA receptor complex in the anxiolytic-like effects of chlordiazepoxide in mice

In the present study, we demonstrated that low, ineffective doses of N-methyl-d-aspartic acid (NMDA) receptor antagonists [competitive NMDA antagonist, CGP 37849, at 0.312 mg/kg intraperitoneally (i.p.), antagonist of the glycineB sites, L-701,324, at 2 mg/kg i.p., partial agonist of glycineB sites, d-cycloserine, at 2.5 mg/kg i.p.] administered jointly with an ineffective dose of the benzodiazepine, chlordiazepoxide (CDP, 2.5 mg/kg i.p.), significantly increased the percentage of time spent in the open arms of the elevated plus-maze (index of anxiolytic effect). Furthermore, CDP-induced anxiolytic-like activity (5 mg/kg i.p.) was antagonized by NMDA (75 mg/kg i.p.) and by an agonist of glycineB sites of the NMDA receptor complex, d-serine [100 nmol/mouse intracerebroventricularly (i.c.v.)]. The present study showed a positive interaction between γ-aminobutyric acid (GABA) and glutamate neurotransmission in the anxiolytic-like activity in the elevated plus-maze test in mice and this activity seems to particularly involve the NMDA receptors

DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker

Neurobiology of rodent self-grooming and its value for translational neuroscience

Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders-including models of autism spectrum disorder and obsessive compulsive disorder-that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.National Institutes of Health (U.S.) (Grant NS025529)National Institutes of Health (U.S.) (Grant HD028341)National Institutes of Health (U.S.) (Grant MH060379

Cognitive-behavioral therapy for obsessive–compulsive disorder: access to treatment, prediction of long-term outcome with neuroimaging

Joseph O'Neill,1 Jamie D Feusner,2 1Division of Child Psychiatry, 2Division of Adult Psychiatry, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA Abstract: This article reviews issues related to a major challenge to the field for obsessive–compulsive disorder (OCD): improving access to cognitive-behavioral therapy (CBT). Patient-related barriers to access include the stigma of OCD and reluctance to take on the demands of CBT. Patient-external factors include the shortage of trained CBT therapists and the high costs of CBT. The second half of the review focuses on one partial, yet plausible aid to improve access – prediction of long-term response to CBT, particularly using neuroimaging methods. Recent pilot data are presented revealing a potential for pretreatment resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy of the brain to forecast OCD symptom severity up to 1 year after completing CBT. Keywords: follow-up, access to treatment, relapse, resting-state fMRI, magnetic resonance spectroscop

Functional connectivity for face processing in individuals with body dysmorphic disorder and anorexia nervosa

Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are both characterized by distorted perception of appearance. Previous studies in BDD suggest abnormalities in visual processing of own and others' faces, but no study has examined visual processing of faces in AN, nor directly compared the two disorders in this respect. Method. We collected functional magnetic resonance imaging data on 60 individuals of equivalent age and gender in each of three groups-20 BDD, 20 weight-restored AN, and 20 healthy controls (HC)-while they viewed images of others' faces that contained only high or low spatial frequency information (HSF or LSF). We tested hypotheses about functional connectivity within specialized sub-networks for HSF and LSF visual processing, using psychophysiological interaction analyses. Results. The BDD group demonstrated increased functional connectivity compared to HC between left anterior occipital face area and right fusiform face area (FFA) for LSF faces, which was associated with symptom severity. Both BDD and AN groups had increased connectivity compared to HC between FFA and precuneous/posterior cingulate gyrus for LSF faces, and decreased connectivity between FFA and insula. In addition, we found that LSF connectivity between FFA and posterior cingulate gyrus was significantly associated with thoughts about own appearance in AN. Conclusions. Results suggest similar abnormal functional connectivity within higher-order systems for face processing in BDD and AN, but distinct abnormal connectivity patterns within occipitooral visual networks. Findings may have implications for understanding relationships between these disorders, and the pathophysiology underlying perceptual distortions

Functional connectivity for face processing in individuals with body dysmorphic disorder and anorexia nervosa

Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are both characterized by distorted perception of appearance. Previous studies in BDD suggest abnormalities in visual processing of own and others' faces, but no study has examined visual processing of faces in AN, nor directly compared the two disorders in this respect. Method. We collected functional magnetic resonance imaging data on 60 individuals of equivalent age and gender in each of three groups-20 BDD, 20 weight-restored AN, and 20 healthy controls (HC)-while they viewed images of others' faces that contained only high or low spatial frequency information (HSF or LSF). We tested hypotheses about functional connectivity within specialized sub-networks for HSF and LSF visual processing, using psychophysiological interaction analyses. Results. The BDD group demonstrated increased functional connectivity compared to HC between left anterior occipital face area and right fusiform face area (FFA) for LSF faces, which was associated with symptom severity. Both BDD and AN groups had increased connectivity compared to HC between FFA and precuneous/posterior cingulate gyrus for LSF faces, and decreased connectivity between FFA and insula. In addition, we found that LSF connectivity between FFA and posterior cingulate gyrus was significantly associated with thoughts about own appearance in AN. Conclusions. Results suggest similar abnormal functional connectivity within higher-order systems for face processing in BDD and AN, but distinct abnormal connectivity patterns within occipitooral visual networks. Findings may have implications for understanding relationships between these disorders, and the pathophysiology underlying perceptual distortions