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Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

To describe the steps of ensuring measurement fidelity of core clinical measures in a five-country study on brain signatures of obsessive-compulsive disorder (OCD).We collected data using standardized instruments, which included the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Dimensional YBOCS (DYBOCS), the Brown Assessment of Beliefs Scale (BABS), the 17-item Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), and the Structured Clinical Interview for DSM-5 (SCID). Steps to ensure measurement fidelity included translating instruments, developing a clinical decision manual, and continuing reliability training with 11-13 transcripts of each instrument by 13 independent evaluators across sites over 4 years. We use multigroup confirmatory factor analysis (MGCFA) to report interrater reliability (IRR) among the evaluators and factor structure for each scale in 206 participants with OCD.The overall IRR for most scales was high (ICC0.94) and remained good to excellent throughout the study. Consistent factor structures (configural invariance) were found for all instruments across the sites, while similarity in the factor loadings for the items (metric invariance) could be established only for the DYBOCS and the BABS.It is feasible to achieve measurement fidelity of clinical measures in multisite, multilinguistic global studies, despite the challenges inherent to such endeavors. Future studies should not only report IRR but also consider reporting methods of standardization of data collection and measurement invariance to identify factor structures of core clinical measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Method: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Results: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Conclusion: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

Objectives: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. Methods: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. Results: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. Conclusions: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

Objective A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children’s Yale−Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes. Method A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively. Results The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7−84.1; specificity = 81.7, 95% CI = 81.5−81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8−82.2; specificity = 84.6, 95% CI = 84.4−84.8). Conclusion Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.

Background Cognitive performance has been studied in adults with obsessive-compulsive symptoms (OCS) and in adult relatives of patients with obsessive-compulsive disorder (OCD) Meanwhile, few studies have been conducted with children under the same conditions. This study compared the neurocognitive domains previously associated with dysfunction in OCD, especially visuoconstructive ability, visuospatial memory, executive functions, and intelligence, in children and adolescents at high risk (HR) for OCD (n = 18) and non-OCD controls (NOC) (n = 31). Methods For the HR group, we considered the first-degree relatives of patients with OCD that present OCS, but do not meet diagnostic criteria for OCD. Psychiatric diagnosis was assessed by experienced clinicians using the Structured Clinical Interview for DSM-IV and OCS severity was measured by the Yale-Brown Obsessive-Compulsive Scale. Neurocognitive assessment was performed with a comprehensive neuropsychological battery. Performance on the cognitive domains was compared between groups using Multivariate Analysis of Variance, whereas performance on the neuropsychological variables was compared between groups using independent t-tests in a cognitive subdomain analysis. Results The cognitive domain analysis revealed a trend towards significance for impairments in the motor and processing speed domain (p = 0.019; F = 3.12) in the HR group. Moreover, the cognitive subdomain analysis identified a statistically significant underperformance in spatial working memory in the HR group when compared to the NOC group (p = 0.005; t = − 2.94), and a trend towards significance for impairments in non-verbal memory and visuoconstructive tasks in the HR group. Conclusions Our results suggest impairments in spatial working memory and motor and processing speed in a non-clinical sample of HR participants. Considering the preliminary nature of our findings, further studies investigating these neurocognitive domains as potential predictors of pediatric OCD are warranted.

Made available in DSpace on 2020-12-12T01:50:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Governo Brasil Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) Background: There is current interest in the elaboration of early intervention programs for obsessive-compulsive disorder (OCD). To this end, it is important to investigate the speed of progression from subthreshold symptoms to diagnosable OCD. In this study, we have retrospectively investigated the speed of progression towards full-blown OCD and sociodemographic and clinical factors associated with a faster transition. Methods: Patients enrolled in the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (N = 954) were interviewed with a comprehensive assessment battery that included the interval (in years) between the onset of subthreshold OCD symptoms and the onset of full-blown OCD. Results: It took a median of 7 years (interquartile range: 2–13 years) for subthreshold symptoms to convert to diagnosable OCD. Faster OCD onset was associated with lower age at the time of assessment, male gender, being in new romantic states as precipitants for compulsions, greater severity of sexual/religious symptoms and lower severity of hoarding and YBOCS compulsions severity scores, greater rates of generalized anxiety disorder and agoraphobia without panic disorder, and negative family history for OCD. Limitations: The retrospective design of this study allowed for susceptibility to memory bias about age at onset of OCD symptoms. We were unable to capture progressions taking less than 12 months. Conclusions: We could identify a specific phenotype that was more likely to escalate rapidly to clinical levels within this large clinical sample. This phenomenon may be particularly relevant in the context of selecting individuals for early intervention initiatives in situations when resources are scarce. Turner Institute for Brain and Mental Health Monash University, 770 Blackburn Road, Clayton Department of Neurology Psychology and Psychiatry Botucatu Medical School Univ Estadual Paulista (UNESP) Department of Psychiatry Federal University of Health Sciences of Porto Alegre (UFCSPA) Department and Institute of Psychiatry University of São Paulo (USP) Department of Psychiatry Federal University of São Paulo (UNIFESP) Obsessive Compulsive and Anxiety Spectrum Research Program. Institute of Psychiatry Federal University of Rio de Janeiro (UFRJ) & D'Or Institute for Research and Education (IDOR), Rio de Janeiro Department of Neurology Psychology and Psychiatry Botucatu Medical School Univ Estadual Paulista (UNESP) Governo Brasil: 302526/2018-8 FAPERJ: CNE E-26/203.052/2017

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has been increasingly examined as an alternative treatment modality for Obsessive-Compulsive Disorder (OCD), due to its low costs, ease of use, and portability. Previous studies have suggested that tDCS may achieve a reasonably good response and present a safe tolerability profile. However, at this point there is not strong evidence for the use of this modality of treatment. Considering that OCD is very heterogeneous with regard to clinical presentation, clinical severity and comorbidities, we have conducted a systematic review of studies on tDCS for OCD aiming to evaluate the clinical characteristics of the selected patients and to discuss perspectives for future studies. A literature search was conducted from inception until March 2019 at PubMed/MedLine and Scielo using the following keywords: "tdcs" or "transcranial direct current stimulation" and "obsessive compulsive disorder". Out of 45 manuscripts, twelve were included. Most of the included studies are uncontrolled. A few controlled studies reported improvement of OCD, but some limitations need to be considered. Our main findings were that the selected patients were adults with severe OCD and psychiatric comorbidities, medicated at the time of assessment and resistant to at least one previous conventional treatment. We could not find any studies including specific populations such as adolescents, elderly, pregnant and breastfeeding participants. Similarly, the potential use of tDCS has not been tested in patients with less severe OCD, as a first treatment option, or for those who do not tolerate pharmacological treatments. These opportunities should be explored in future controlled trials.

Introduction: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation intervention that has been investigated for several psychiatric disorders, including Obsessive-Compulsive Disorder (OCD). As there are several candidate brain regions for targeting OCD relevant networks, clinical studies using tDCS have considerably varied in terms of the electrode montages used. Computer modeling of electric field currents induced by tDCS can help guiding the research of relevant targets for OCD. In this review, the authors used this tool to investigate targeted brain areas from previous studies of tDCS in OCD. Areas covered: A literature search for articles with the keywords 'tDCS', 'Transcranial Direct Current Stimulation' and 'Obsessive Compulsive Disorder' was conducted to identify relevant publications. For comparing different electrode montages, electric field (EF) models were performed using high-resolution brain scan templates. Authors found 13 studies mostly showing an improvement in OCD symptoms. The electrode montages varied considerably between studies. Nonetheless, two main patterns of EFs could be identified: 'focal montages', with EFs concentrated in the prefrontal cortex, and 'diffuse montages', with widespread EFs over cortical areas. Expert opinion: Electric field simulation can guide future clinical trials in psychiatry, using personalized tDCS montages with distinct electrode positioning according to clusters of symptoms.

Background: Recent studies using magnetic resonance spectroscopy (1H-MRS) indicate that patients with obsessive–compulsive disorder (OCD) present abnormal levels of glutamate (Glu) and gamma aminobutyric acid (GABA) in the frontal and striatal regions of the brain. These abnormalities could be related to the hyperactivation observed in cortico-striatal circuits of patients with OCD. However, most of the previous 1H-MRS studies were not capable of differentiating the signal from metabolites that overlap in the spectrum, such as Glu and glutamine (Gln), and referred to the detected signal as the composite measure—Glx (sum of Glu and Gln). In this study, we used a two-dimensional JPRESS 1H-MRS sequence that allows the discrimination of overlapping metabolites by observing the differences in J-coupling, leading to higher accuracy in the quantification of all metabolites. Our objective was to identify possible alterations in the neurometabolism of OCD, focusing on Glu and GABA, which are key neurotransmitters in the brain that could provide insights into the underlying neurochemistry of a putative excitatory/inhibitory imbalance. Secondary analysis was performed including metabolites such as Gln, creatine (Cr), N-acetylaspartate, glutathione, choline, lactate, and myo-inositol.Methods: Fifty-nine patients with OCD and 42 healthy controls (HCs) underwent 3T 1H-MRS in the ventromedial prefrontal cortex (vmPFC, 30 × 25 × 25 mm3). Metabolites were quantified using ProFit (version 2.0) and Cr as a reference. Furthermore, Glu/GABA and Glu/Gln ratios were calculated. Generalized linear models (GLMs) were conducted using each metabolite as a dependent variable and age, sex, and gray matter fraction (fGM) as confounding factors. GLM analysis was also used to test for associations between clinical symptoms and neurometabolites.Results: The GLM analysis indicated lower levels of Glu/Cr in patients with OCD (z = 2.540; p = 0.011). No other comparisons reached significant differences between groups for all the metabolites studied. No associations between metabolites and clinical symptoms were detected.Conclusions: The decreased Glu/Cr concentrations in the vmPFC of patients with OCD indicate a neurochemical imbalance in the excitatory neurotransmission that could be associated with the neurobiology of the disease and may be relevant for the pathophysiology of OCD.

Background While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients. Methods We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication. Results Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures. Conclusions Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory.

This article reviews recent advances in the genetics of obsessive-compulsive disorder (OCD). We cover work on the following: genome-wide association studies, whole-exome sequencing studies, copy number variation studies, gene expression, polygenic risk scores, gene-environment interaction, experimental animal systems, human cell models, imaging genetics, pharmacogenetics, and studies of endophenotypes. Findings from this work underscore the notion that the genetic architecture of OCD is highly complex and shared with other neuropsychiatric disorders. Also, the latest evidence points to the participation of gene networks involved in synaptic transmission, neurodevelopment, and the immune and inflammatory systems in this disorder. We conclude by highlighting that further study of the genetic architecture of OCD, a great part of which remains to be elucidated, could benefit the development of diagnostic and therapeutic approaches based on the biological basis of the disorder. Studies to date revealed that OCD is not a simple homogeneous entity, but rather that the underlying biological pathways are variable and heterogenous. We can expect that translation from bench to bedside, through continuous effort and collaborative work, will ultimately transform our understanding of what causes OCD and thus how best to treat it.

Made available in DSpace on 2021-06-25T12:35:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: Obsessive-compulsive disorder (OCD) is a very heterogeneous condition that frequently includes symptoms of the symmetry dimension (i.e., obsessions and/or compulsions of symmetry, ordering, repetition, and counting), along with aggressive, sexual/religious, contamination/cleaning, and hoarding dimensions. Methods: This cross-sectional study aimed to investigate the prevalence, severity, and demographic and clinical correlates of the symmetry dimension among 1001 outpatients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders. The main assessment instruments used were the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale-Brown Obsessive-Compulsive Scale, the USP-Sensory Phenomena Scale, the Beck Depression and Anxiety Inventories, the Brown Assessment of Beliefs Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Chi-square tests, Fisher's exact tests, Student's t-tests, and Mann-Whitney tests were used in the bivariate analyses to compare patients with and without symptoms of the symmetry dimension. Odds ratios (ORs) with confidence intervals and Cohen's D were also calculated as effect size measures. Finally, a logistic regression was performed to control for confounders. Results: The symmetry dimension was highly prevalent (86.8%) in this large clinical sample and, in the logistic regression, it remained associated with earlier onset of obsessive-compulsive symptoms, insidious onset of compulsions, more severe depressive symptoms, and presence of sensory phenomena. Conclusions: A deeper knowledge about specific OCD dimensions is essential for a better understanding and management of this complex and multifaceted disorder. Univ Estadual Paulista UNESP, Botucatu Med Sch, Dept Neurol Psychol & Psychiat, BR-18618687 Botucatu, SP, Brazil Monash Univ, Turner Inst Brain & Mental Hlth, Clayton, Vic 3168, Australia Univ Fed Rio de Janeiro, DOr Inst Res & Educ, BR-22290140 Rio De Janeiro, Brazil Univ Fed Rio de Janeiro, Inst Psychiat, BR-22290140 Rio De Janeiro, Brazil Univ Sao Paulo, Dept & Inst Psychiat, Obsess Compuls Spectrum Disorders Program, BR-05403010 Sao Paulo, Brazil Fed Univ Hlth Sci Porto Alegre, Dept Psychiat, BR-90570080 Porto Alegre, RS, Brazil Univ Fed Sao Paulo, Dept Psychiat, BR-04038000 Sao Paulo, Brazil Univ Estadual Paulista UNESP, Botucatu Med Sch, Dept Neurol Psychol & Psychiat, BR-18618687 Botucatu, SP, Brazil

Made available in DSpace on 2020-12-12T02:19:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) Background: While stressful life events increase the risk of developing a range of psychiatric disorders, including obsessive-compulsive disorder (OCD), their ability to precipitate specific obsessive-compulsive symptoms' dimensions is unknown. Here we aimed to evaluate the potential role of three different types of stressful life events, herein termed losses (death of a loved one, termination of a romantic relationship and severe illness) in predicting the speed of progression from subclinical to clinical OCD and the severity of specific OCD dimensions in a large multicentre OCD sample. Methods: Nine hundred and fifty-four OCD outpatients from the Brazilian OCD Research Consortium were included in this study. Several semi-structured and structured instruments were used, including the Structured Clinical Interview for DSM-IV Axis I Disorders, the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Brown Assessment of Beliefs Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Yale OCD Natural History Questionnaire. Regression models investigated the interaction between types of loss and gender to predict speed of progression from subclinical obsessive-compulsive symptoms to OCD, and the severity of five symptom dimensions. Results: While termination of a relationship was associated with a faster speed of progression from subthreshold to clinical OCD, the death of a loved one was associated with increased severity of hoarding symptoms. There was also an interaction between gender and experiences of death, which predicted a faster speed of progression to OCD in males. Conclusions: Stressful life events have the ability to accelerate the progression from subclinical to clinical OCD, as well as impact the severity of specific OCD dimensions. Gender also plays a role in both the progression and severity of symptoms. These findings suggest that stressful life events may represent a marker to identify individuals at risk of progressing to clinical OCD. Brain & Mental Health Research Hub Turner Institute for Brain and Mental Health Monash University Department of Neurology Psychology and Psychiatry Botucatu Medical School Universidade Estadual Paulista (Unesp) Department of Psychiatry Federal University of Health Sciences of Porto Alegre (UFCSPA) Obsessive-Compulsive Spectrum Disorders Program (PROTOC) Department and Institute of Psychiatry University of São Paulo (USP) Obsessive Compulsive and Anxiety Spectrum Research Program. Institute of Psychiatry Federal University of Rio de Janeiro & D'Or Institute for Research and Education Department of Neurology Psychology and Psychiatry Botucatu Medical School Universidade Estadual Paulista (Unesp) FAPERJ: CNE E−26/203.052/2017

Obsessive-compulsive disorder (OCD) is a frequent, disabling disorder with high rates of treatment resistance. Transcranial direct current stimulation (tDCS) is a safe, tolerable noninvasive neuromodulation therapy with scarce evidence for OCD. This double-blind, randomized, and sham-controlled study investigates the efficacy of tDCS as add-on treatment for treatment-resistant OCD (failure to respond to at least one previous pharmacological treatment). On 20 consecutive weekdays (4 weeks), 43 patients with treatment-resistant OCD underwent 30 min active or sham tDCS sessions, followed by a 8 week follow-up. The cathode was positioned over the supplementary motor area (SMA) and the anode over the left deltoid. The primary outcome was the change in baseline Y-BOCS score at week 12. Secondary outcomes were changes in mood and anxiety and the occurrence of adverse events. Response was evaluated considering percent decrease of baseline Y-BOCS scores and the Improvement subscale of the Clinical Global Impression (CGI-I) between baseline and week 12. Patients that received active tDCS achieved a significant reduction of OCD symptoms than sham, with mean (SD) Y-BOCS score changes of 6.68 (5.83) and 2.84 (6.3) points, respectively (Cohen's d: 0.62 (0.06-1.18), p = 0.03). We found no between-group differences in responders (four patients in the active tDCS and one in the sham group). Active tDCS of the SMA was not superior to sham in reducing symptoms of depression or anxiety. Patients in both groups reported mild adverse events. Our results suggest that cathodal tDCS over the SMA is an effective add-on strategy in treatment-resistant OCD.

Objectives: The Yale-Brown Obsessive-Compulsive Scale has been considered the gold standard scale to assess obsessive-compulsive disorder severity. Previous studies using exploratory factor analysis and confirmatory factor analysis with this scale showed mixed findings in terms of factor structure and fit of models. Therefore, we used confirmatory factor analysis to compare different Yale-Brown Obsessive-Compulsive Scale models in a large sample aiming to identify the best model fit. Methods: We assessed adult obsessive-compulsive disorder patients ( n = 955) using three measures: Yale-Brown Obsessive-Compulsive Scale severity ratings, the Dimensional Yale-Brown Obsessive-Compulsive Scale and the clinical global impression scale. We tested all factor structures reported by previous studies to investigate which model best fitted the data: one-factor, two-factor, three-factor and their equivalent high-order solutions. We also investigated Yale-Brown Obsessive-Compulsive Scale items correlations with scores from the other measures of obsessive-compulsive disorder severity. Results: Confirmatory factor analysis models presented mediocre to fair goodness-of-fit indexes. Severity items related to resistance to obsessions and compulsions presented low factor loadings. The model with the best fit indexes was a high-order model without obsessive-compulsive disorder resistance items. These items also presented small correlations with other obsessive-compulsive disorder severity measures. Conclusion: The obsessive-compulsive disorder field needs to discuss further improvements in the Yale-Brown Obsessive-Compulsive Scale and/or continue to search for better measures of obsessive-compulsive disorder severity.

BackgroundObsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results.MethodsWe will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations.DiscussionUsing harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed., International Clinical Psychopharmacology, 35 (4), ISSN:0268-1315, ISSN:1473-5857

Supplemental material, Supplementary_Material for Is it time to change the gold standard of obsessive-compulsive disorder severity assessment? Factor structure of the Yale-Brown Obsessive-Compulsive Scale by Daniel Fatori, Daniel LC Costa, Fernando R Asbahr, Ygor A Ferrão, Maria Conceição Rosário, Euripedes C Miguel, Roseli G Shavitt and Marcelo C Batistuzzo in Australian & New Zealand Journal of Psychiatry

Objectives: To assess the rates of co-occurring putative ‘behavioural addictions’ in patients with obsessive-compulsive disorder (OCD). Methods: Twenty-three international centres specialising in the treatment of OCD were invited to participate in a survey of the rates of behavioural addictions and other relevant comorbidity within their samples. Results: Sixteen of 23 (69.6%) invited centres from 13 countries had sufficient data to participate in the survey. The use of validated diagnostic tools was discrepant, with most centres relying on a ‘clinical diagnosis’ to diagnose behavioural addictions. The final sample comprised of 6916 patients with a primary diagnosis of OCD. The reported rates of behavioural addictions were as follows: 8.7% for problematic internet use, 6.8% for compulsive sexual behaviour disorder, 6.4% for compulsive buying, 4.1% for gambling disorder and 3.4% for internet gaming disorder. Conclusions: Behavioural addictions should be better assessed for patients with OCD. The absence of diagnostic scales developed specifically for behavioural addictions and overlapping obsessive-compulsive phenomena such as compulsive checking of information on the internet may explain the relatively high rate of problematic internet use in this sample. The study encourages better efforts to assess and to conceptualise the relatedness of behavioural addictions to obsessive-compulsive ‘spectrum’ disorders.

Obsessive-compulsive disorder (OCD) is a chronic, debilitating, and heterogeneous condition that affects 2–3% of the general population. Previous studies have suggested that sex plays a role in OCD phenotypic expression. This chapter aims to review the literature regarding OCD in women, exploring sex differences in (1) the prevalence of OCD/subclinical OCD in nonclinical populations; (2) age of onset, clinical course, and severity and impact of OCD symptoms; (3) onset or aggravation of OCD symptoms among women according to the time point in the reproductive cycle; (4) OCD symptom contents; (5) psychiatric comorbidity; and (6) treatment-seeking behavior and treatment response. Studies report either a slight female predominance or a similar prevalence of OCD in adults from the general population. Women are more likely than men to be married, to present later onset, and to report preceding stressful life events. Onset or worsening of OCD symptoms during pregnancy and postpartum are frequently described. Women are more likely to present contamination obsessions and/or cleaning rituals and comorbid eating and impulse-control disorders. Several interacting mechanisms are probably responsible for mediating the effects of sex/gender in the biological and psychosocial risk factors for OCD. Sex is a relevant factor that should be taken into account when evaluating OCD patients, but more studies are necessary to determine whether or not it defines a valid OCD subtype.

Objective This sequential multiple assignment randomized trial (SMART) tested the effect of beginning treatment of childhood OCD with fluoxetine (FLX) or group cognitive-behavioral therapy (GCBT) accounting for treatment failures over time. Methods A two-stage, 28-week SMART was conducted with 83 children and adolescents with OCD. Participants were randomly allocated to GCBT or FLX for 14 weeks. Responders to the initial treatment remained in the same regimen for additional 14 weeks. Non-responders, defined by less than 50% reduction in baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, were re-randomized to either switch to or add the other treatment. Assessments were performed at baseline, 7, 14, 21, and 28 weeks. Results Among the 43 children randomized to FLX who completed the first stage, 15 (41.7%) responded to treatment and 21 non-responders were randomized to switch to (N = 9) or add GCBT (N = 12). Among the 40 children randomized to GCBT who completed the first stage, 18 (51.4%) responded to treatment and 17 non-responders were randomized to switch to (N = 9) or add FLX (N = 8). Primary analysis showed that significant improvement occurred in children initially treated with either FLX or GCBT. Each time point was statistically significant, showing a linear trend of symptom reduction. Effect sizes were large within (0.76–0.78) and small between (-0.05) groups. Conclusions Fluoxetine and GCBT are similarly effective initial treatments for childhood OCD considering treatment failures over time. Consequently, provision of treatment for childhood OCD could be tailored according to the availability of local resources.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for Research Support in the State of Sao Paulo) [2011/51485-9, 2012/14070-8]

The aims of this study were (1) to assess obsessive-compulsive symptoms (OCS) dimensionally in a school-aged community sample and to correlate them with clinical and demographical variables; (2) to determine a subgroup with significant OCS ("at-risk for OCD") using the Child Behavior Checklist (CBCL-OCS) and (3) to compare it with the rest of the sample; (4) To review the CBCL-OCS subscale properties as a screening tool for pediatric OCD.Data from the Brazilian High Risk Cohort were analyzed. The presence and severity of OCS were assessed through the CBCL-OCS subscale. DSM-IV psychiatric diagnoses were obtained by the Developmental and Well-Being Assessment. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire, the Youth Strengths Inventory, and the CBCL internalizing and externalizing behavior subscales.A total of 2512 (mean age: 8.86 ± 1.84 years; 55.0% male) children were included. Moderate correlations were found between OCS severity and functional impairment (r = 0.36, p 0.001). Children with higher levels of OCS had higher rates of psychiatric comorbidity and behavioral problems (p 0.001). A score of 5 or higher in the CBCL-OCS scale determined an "at-risk for OCD" subgroup, comprising 9.7% of the sample (n = 244), with behavioral patterns and psychiatric comorbidities (e.g., tics [odds ratios, OR = 6.41, p 0.001]), anxiety disorders grouped [OR = 3.68, p 0.001] and depressive disorders [OR = 3.0, p 0.001] very similar to those described in OCD. Sensitivity, specificity, positive predictive value, and negative predictive value of the CBCL-OCS for OCD diagnosis were, respectively, 48%, 91.5%; 15.1%, and 98.2%.The dimensional approach suggests that the presence of OCS in children is associated with higher rates of comorbidity, behavioral problems, and impairment. The "at-risk for OCD" group defined by the CBCL revealed a group of patients phenotypically similar to full blown OCD.

Obsessive-compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the 'obsessive-compulsive and related disorders', a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive-behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.

Differences in hippocampus volume have been identified in adult patients with obsessive-compulsive disorder (OCD). However, the role of this limbic structure in pediatric patients is unclear. This study aimed to investigate the hippocampus and its subregions in a sample of 29 children and adolescents with OCD compared to 28 healthy controls, matched for age, sex, education, and IQ. Volumetric segmentation was performed using the Freesurfer software to calculate the volumes of the subregions that reflect the hippocampal cytoarchitecture. The volumes of three anatomic subregions (tail, body, and head) were also calculated. ANCOVA was performed to investigate differences of these volumes between patients and controls, controlling for total gray matter volume. After Bonferroni correction for multiple comparisons (p-value0.00556 for the body and0.00625 for the head structures), patients presented statistically significant larger volumes of the following structures: left subiculum body; left CA4 body; left GC-DG body; left molecular layer body; right parasubiculum; left CA4 head; left molecular layer head; right subiculum head and right molecular layer head. These enlarged volumes resulted in larger left and right whole hippocampi in patients, as well as bilateral hippocampal heads and left hippocampal body (all p-values0.00625). There were no associations between OCD severity and hippocampal volumes. These findings diverge from previous reports on adults and may indicate that larger hippocampal volumes could reflect an early marker of OCD, not present in adults.

Attentional bias (AB) refers to increased allocation of attention on threat stimuli when compared to neutral stimuli. It is not clear if AB occurs in subjects with obsessive-compulsive disorder (OCD). We tested AB for symmetry and cleaning symptoms of OCD. Sixty-two patients with OCD and 40 healthy controls matched by gender, age and IQ, completed a computerized dot-probe task where two pictures (with symmetry or cleaning related content) were shown. The probe appeared in the location previously occupied by one of the pictures. Within-subjects linear mixed-effect models were used to investigate the effects of the factors: group (patients vs controls), OCD dimension (cleaning vs symmetry), task condition (neutral, congruent and incongruent), and the interaction among them. We also correlated AB scores with the clinical and demographic variables. No positive interaction resulted among the factors, but positive results were observed in group and condition, separately. Patients were significantly slower than controls (p-value = 0.014) (an effect that was accounted for by depression and anxiety symptoms and comorbidity) and the neutral condition was significantly faster when compared the other two conditions (congruent and incongruent, p-value = 0.013). No association was found between AB scores and clinical symptoms. There was no AB toward specific, content-related, stimuli in this sample of OCD patients.

Made available in DSpace on 2019-10-06T16:34:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: Patients with obsessive-compulsive disorder (OCD) often present with comorbidities, mainly anxiety and affective disorders, which may influence OCD course, help-seeking and treatment response. Some authors have studied bipolar disorder (BD) comorbidity in patients with OCD, but usually in small samples. The objective was to estimate the lifetime prevalence of BD in a large clinical sample of OCD patients, and to compare demographic and clinical features of patients with and without BD comorbidity. Method: This cross-sectional study with 955 adult OCD patients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC) used several assessment instruments, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Beck Depression and Anxiety Inventories, and the Structured Clinical Interview for DSM-IV Axis I Disorders. Descriptive and bivariate analyses were followed by logistic regression. Results: The lifetime prevalence of BD was 7.75% (N = 74). The variables that were independently associated with BD comorbidity were: panic disorder with agoraphobia, impulse control disorders, and suicide attempts. Limitations: The cross-sectional design does not permit causal inferences; the external validity may be limited, as the participants were from tertiary services. Despite the large sample size, some analyses may have been underpowered due to the relatively low prevalence of the outcome and of some explanatory variables. Conclusions: Patients with OCD comorbid with BD have some clinical features indicative of greater severity, including higher suicide risk, and require a careful therapeutic approach for the appropriate treatment of both disorders. Department of Neurology Psychology and Psychiatry Botucatu Medical School Univ Estadual Paulista (UNESP) Department and Institute of Psychiatry University of São Paulo (USP) Department of Psychiatry and Legal Medicine Federal University of Rio de Janeiro D'Or Institute for Research and Education Monash Institute of Cognitive and Clinical Neurosciences Monash University Department of Psychiatry Federal University of Health Sciences of Porto Alegre Department of Psychiatry Federal University of São Paulo (UNIFESP) Department of Neurology Psychology and Psychiatry Botucatu Medical School Univ Estadual Paulista (UNESP) FAPESP: 2005/ 55628-8 CNPq: 573974/2008-0

Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the 'toxic' effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed. (C) 2019 Elsevier B.V. and ECNP. All rights reserved.

Background Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. In recent years, risk gene discovery in other complex psychiatric disorders has been achieved by studying rare de novo (DN) coding variants. Methods We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), comparing DN variant frequencies with 777 previously sequenced unaffected trios. We estimated the contribution of DN mutations to OCD risk and the number of genes involved. Finally, we looked for gene enrichment in other datasets and canonical pathways. Results DN likely gene disrupting and predicted damaging missense variants are enriched in OCD probands (rate ratio, 1.52; p = .0005) and contribute to risk. We identified 2 high-confidence risk genes, each containing 2 DN damaging variants in unrelated probands: CHD8 and SCUBE1. We estimate that 34% of DN damaging variants in OCD contribute to risk and that DN damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring DN damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly Tourette’s disorder and autism spectrum disorder. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways, biological processes, and disease networks. Conclusions Our findings show a pathway toward systematic gene discovery in OCD via identification of DN damaging variants. Sequencing larger cohorts of OCD parent-child trios will reveal more OCD risk genes and will provide needed insights into underlying disease biology.

Key Points Question Is lateral hypothalamic deep brain stimulation (DBS) safe for the treatment of obesity in Prader-Willi syndrome? Findings In this case series of 4 patients with Prader-Willi syndrome treated with lateral hypothalamic DBS, 2 developed stimulation-induced manic symptoms and 2 developed infections, 1 of which was associated with skin picking. No major differences were found when postoperative anthropometric and calorimetric data were compared with baseline; hormonal levels, and results of blood workup, sleep studies, and neuropsychological evaluations also showed no change. Meaning Safety of lateral hypothalamic DBS was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS; however, in the small cohort of patients with Prader-Willi syndrome treated, DBS seemed largely ineffective for the treatment of obesity., This study of a case series of 4 patients investigates the safety and efficacy of deep brain stimulation for obesity associated with Prader-Willi syndrome., Importance Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.

Objectives To assess rates of psychotropic medication use in patients with obsessive–compulsive disorder (OCD) in seven different countries on five continents and to compare these with international treatment guidelines. Methods Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their patients with OCD and on their incidence of psychotropic use. Consistency of summary statistics across countries was evaluated. Results The data came from Brazil (n = 955), Italy (n = 750), South Africa (n = 555), Japan (n = 382), Australia (n = 213), India (n = 202) and Spain (n = 82). The majority (77.9%; n = 2445) of the total sample of 3139 participants received a psychotropic medication. Consistent with international guidelines, selective serotonin reuptake inhibitors (SSRIs) were most commonly used (73.5%, n = 1796), but their use ranged from 59% in Australia to 96% in Japan. Clomipramine use varied from 5% in Japan and South Africa to 26% in India and Italy. Atypical antipsychotic use ranged from 12% in South Africa to 50% in Japan. Conclusions Pharmacotherapy for OCD varied significantly across sites. Prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that may play a role in the variation in prescribing practices internationally and whether these variations influence treatment outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Individuals with obsessive-compulsive disorder (OCD) who sought treatment in seven different specialized centers (n=1001) were evaluated with a structured assessment battery. Thirteen OCD patients (1.3% of the sample) reported having been treated with electroconvulsive therapy (ECT) in the past. They were older and exhibited higher global severity of OCD symptoms, but were less likely to display symmetry/ordering and contamination/washing symptoms. They also had greater suicidality and increased rates of psychosis. Finally, OCD patients exposed to ECT were more frequently treated with antipsychotics, although they did not differ in terms of responses to adequate trials with serotonin reuptake inhibitors.

This study aimed to determine the frequency of benzodiazepine (BDZ) use in a large sample of patients with obsessive-compulsive disorder (OCD) and ascertain the type of BDZ used and the correlates and predictors of BDZ use in OCD. The sample consisted of 955 patients with OCD from a comprehensive, cross-sectional, multicentre study conducted by the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders between 2003 and 2009. The rate of BDZ use over time in this OCD sample was 38.4%. Of individuals taking BDZs, 96.7% used them in combination with other medications, usually serotonin reuptake inhibitors. The most commonly used BDZ was clonazepam. Current age, current level of anxiety and number of additional medications for OCD taken over time significantly predicted BDZ use. This is the first study to comprehensively examine BDZ use in OCD patients, demonstrating that it is relatively common, despite recommendations from treatment guidelines. Use of BDZs in combination with several other medications over time and in patients with marked anxiety suggests that OCD patients taking BDZs may be more complex and more difficult to manage. This calls for further research and clarification of the role of BDZs in the treatment of OCD.

Objective The aim of the present study was to examine the intellectual quotient (IQ) in a large sample of youth with obsessive-compulsive disorder (OCD) and to compare them with typically developing individuals (TDI), adding to the scarce literature focusing on the intelligence evaluation of this population. Method The IQ of 82 children and adolescents with OCD and 82 TDI, matched by age, sex, handedness and education, was assessed by the Wechsler Abbreviated Scale of Intelligence (WASI, Brazilian-version). Statistics were performed with independent t-test, correlations and ANCOVA (controlling for motor and processing speed and comorbidities), corrected using the Benjamini-Hochberg multiple comparisons correction. Results No between-group differences were found on the full-scale IQ (FSIQ, p-value = 0.545) or verbal IQ (VIQ; p-value = 0.423). In contrast, a significant difference was found in the performance IQ (PIQ; p-value = 0.045, Cohen's d = 0.379) and IQ discrepancy, i.e. the difference between VIQ and PIQ (p-value = 0.012, Cohen's d = 0.494). Analyses of the PIQ subtest scores revealed impaired performance in the Block Design test among OCD patients (p-value = 0.012, Cohen's d = 0.273), that remained after correcting for motor and processing speed and comorbidity status. Conclusion In our sample of pediatric patients with OCD, the FSIQ, VIQ and PIQ were within the average range (90-110), and we did not find between-group differences in the FSIQ or VIQ, indicating that youth with OCD do not present major deficits in intellectual efficiency. Nevertheless, replicating an extensive adult literature, we found lower PIQ scores in youth patients, that were not better explained by motor and processing speed or comorbidity status.