Social skills in patients with obsessive-compulsive disorder before and after treatment.

OBJECTIVE: We aim to investigate whether: 1) social skills (SS) are impaired in obsessive-compulsive disorder (OCD); 2) SS would change over the course of treatment; and 3) severity of OCD, age of onset of OCD symptoms and illness duration would be associated with SS impairments. METHODS: 41 treatment-naive patients with OCD and 34 control participants (CP) were assessed using a SS inventory. Patients were reevaluated 12-weeks after standardized treatment. Group differences, as well as the treatment effect on OCD symptomatology over time, were analyzed with independent and paired tests, respectively. OCD severity, age at illness onset and illness duration were tested as predictors of SS. RESULTS: Patients had lower total SS scores compared to controls (p-value < 0.001). After treatment, although OCD symptomatology (p-value < 0.001) improved, there was no statistical difference in SS performance (p-value = 0.673). Earlier age of onset of OCD symptoms predicted worse SS total score (p-value = 0.016). CONCLUSION: This study suggests that, despite the amelioration of OCD symptomatology, there was no alteration in Social Skills (SS) performance. Subsequent treatment investigations incorporating larger sample sizes and extended follow-up periods could elucidate whether enhancements in social skills are likely to manifest over time.

Impact of the COVID-19 pandemic on the symptomatology and routine of medicated patients with obsessive-compulsive disorder.

OBJECTIVES: To study the impact of coronavirus disease 2019 on the routine of patients with obsessive-compulsive disorder (OCD) and changes in symptoms and suicidal-related behavior, mainly in those with cleaning symptoms. METHODS: In this cross-sectional study, 58 patients completed an online self-report questionnaire that included the Obsessive-Compulsive Inventory-Revised, Coronavirus Stress and Traumatic Events Scale, Coronavirus Health Impact Survey, Beck Anxiety and Beck Depression inventories, and Suicide-Related Behaviors Questionnaire. Comparisons were made with another pre-pandemic sample (n=524) regarding the last three measures. RESULTS: During the pandemic, the patients spent more days inside their homes (χ² = 33.39, p = 0.007), changed their alcohol consumption patterns (χ² = 87.6, p < 0.001), and increased social media usage (χ² = 68.83, p < 0.001). Participants with cleaning symptoms did not significantly differ from the others in relation to stress, anxiety/depressive symptoms, or suicidal-related behaviors. Finally, our sample did not differ from an equivalent OCD sample assessed before the pandemic in terms of anxiety and depressive symptom severity or suicidal-related behaviors. CONCLUSION: Overall, patients with OCD showed no lifestyle changes associated with higher stress levels during the pandemic. Patients with and without cleaning symptoms and patients before and during the pandemic presented similar results.

Impact of the COVID-19 pandemic on the symptomatology and routine of medicated patients with obsessive-compulsive disorder

Objectives: To study the impact of coronavirus disease 2019 on the routine of patients with obsessive-compulsive disorder (OCD) and changes in symptoms and suicidal-related behavior, mainly in those with cleaning symptoms. Methods: In this cross-sectional study, 58 patients completed an online self-report questionnaire that included the Obsessive-Compulsive Inventory-Revised, Coronavirus Stress and Traumatic Events Scale, Coronavirus Health Impact Survey, Beck Anxiety and Beck Depression inventories, and Suicide-Related Behaviors Questionnaire. Comparisons were made with another pre-pandemic sample (n=524) regarding the last three measures. Results: During the pandemic, the patients spent more days inside their homes (χ2 = 33.39, p = 0.007), changed their alcohol consumption patterns (χ2 = 87.6, p < 0.001), and increased social media usage (χ2 = 68.83, p < 0.001). Participants with cleaning symptoms did not significantly differ from the others in relation to stress, anxiety/depressive symptoms, or suicidal-related behaviors. Finally, our sample did not differ from an equivalent OCD sample assessed before the pandemic in terms of anxiety and depressive symptom severity or suicidal-related behaviors. Conclusion: Overall, patients with OCD showed no lifestyle changes associated with higher stress levels during the pandemic. Patients with and without cleaning symptoms and patients before and during the pandemic presented similar results.

Clinical characteristics of probands with obsessive-compulsive disorder from simplex and multiplex families.

Genetic and non-genetic factors contribute to obsessive-compulsive disorder (OCD), with strong evidence of familial clustering. Genomic studies in psychiatry have used the concepts of families that are "simplex" (one affected) versus "multiplex" (multiple affected). Our study compares demographic and clinical data from OCD probands in simplex and multiplex families to uncover potential differences. We analyzed 994 OCD probands (501 multiplex, 493 simplex) from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Clinicians administered the Structured Clinical Interview for DSM-IV (SCID-IV) to diagnose, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess severity, and Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) to assess symptom dimensionality. Demographics, clinical history, and family data were collected. Compared to simplex probands, multiplex probands had earlier onset, higher sexual/religious and hoarding dimensions severity, increased comorbidity with other obsessive-compulsive-related disorders (OCRD), and higher family history of psychiatric disorders. These comparisons provide the first insights into demographic and clinical differences between Latin American simplex and multiplex families with OCD. Distinct clinical patterns may suggest diverse genetic and environmental influences. Further research is needed to clarify these differences, which have implications for symptom monitoring and management.

Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research.

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.

Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research

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.

Systematic Review and Meta-analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric Obsessive-Compulsive Disorder.

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.

Lower Ventromedial Prefrontal Cortex Glutamate Levels in Patients With Obsessive-Compulsive Disorder.

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.

Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder.

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.

Symmetry Dimension in Obsessive-Compulsive Disorder: Prevalence, Severity and Clinical Correlates.

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.

Higher volumes of hippocampal subfields in pediatric obsessive-compulsive disorder.

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-value < 0.00556 for the body and < 0.00625 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-values < 0.00625). 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.

Social losses predict a faster onset and greater severity of obsessive-compulsive disorder.

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.

Is it time to change the gold standard of obsessive-compulsive disorder severity assessment? Factor structure of the Yale-Brown Obsessive-Compulsive Scale.

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.

The speed of progression towards obsessive-compulsive disorder.

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.

Cutting-edge genetics in obsessive-compulsive disorder.

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.

De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.

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.

Bipolar disorder comorbidity in patients with obsessive-compulsive disorder: Prevalence and predictors.

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.