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Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls., Results: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences., Conclusions: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD., (© 2021. The Author(s).)

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Introduction: Compulsive buying (CB) is currently classified as an impulse control disorder (ICD) not otherwise classified. Compulsive buying prevalence is estimated at around 5% of the general population. There is controversy about whether CB should be classified as an ICD, a subsyndromal bipolar disorder (BD), or an obsessive-compulsive disorder (OCD) akin to a hoarding syndrome. To further investigate the appropriate classification of CB, we compared patients with CB, BD, and OCD for impulsivity, affective instability, hoarding, and other OCD symptoms., Method: Eighty outpatients (24 CB, 21 BD, and 35 OCD) who were neither manic nor hypomanic were asked to fill out self-report questionnaires., Results: Compulsive buying patients scored significantly higher on all impulsivity measures and on acquisition but not on the hoarding subdimensions of clutter and "difficulty discarding." Patients with BD scored higher on the mania dimension from the Structured Clinical Interview for Mood Spectrum scale. Patients with OCD scored higher on obsessive-compulsive symptoms and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients with CB (79%), BD (71%), and OCD (77%)., Conclusion: Patients with CB came out as impulsive acquirers, resembling ICD- rather than BD- or OCD-related disorders. Manic symptoms were distinctive of patients with BD. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To study clinical and psychopathological features of obsessive-compulsive disorder (OCD) in women with bipolar disorder (BD)., Methods: Fifteen outpatients with concurrent bipolar disorder I (80.0%) or II (20.0%) and obsessive-compulsive disorder were studied. Most of them (80.0%) sought treatment for bipolar disorder. They were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID/P), semi-structured interviews to investigate obsessions, compulsions and sensory phenomena that may precede compulsions and an additional module for the diagnosis of chronic motor and vocal tics. Severity of symptoms was assessed by the Yale-Brown Obsessive-Compulsive Rating Scale, Hamilton Depression Rating Scale and Young Mania Rating Scale., Results: Obsessive-compulsive disorder presented early onset (before the age of 10) in 9 (60%) cases, preceded bipolar disorder in 10 (66.7%) and displayed chronic waxing and waning course in 13 (86.7%) of them. There was wide overlap between types of obsessive-compulsive symptoms and all patients experienced sensory phenomena preceding the compulsions. There was no clear-cut impact of depressive and manic episodes on the intensity of obsessive-compulsive symptoms, which increased in depression and decreased in mania in 40.0% of the cases, had the opposite pattern in 26.7% of the patients and fluctuated inconsistently in the rest of them. Tics disorders were diagnosed in 5 (33.3%) patients., Conclusions: Our results suggest that in women with comorbid bipolar disorder and obsessive-compulsive disorder the latter presents features that may be typical of the association of the two disorders, such as early onset and sensory phenomena preceding compulsions. A prospective controlled study is necessary to confirm these observations, due to some limitations of our study: small exclusively female sample, heterogeneity concerning the type of bipolar disorder and the disorder that determined sought of treatment and retrospective non-controlled design.

de Macedo-Soares MB, Brietzke E, da Silva Dias R, Mendonca T, Moreira C, Lafer B. A comparison of the symptomatic profile between two consecutive depressive episodes in patients with bipolar disorder type I. To compare the variability of patterns of depressive symptoms between two consecutive depressive episodes in patients with bipolar disorder type I. Review of prospectively collected data from 136 subjects of an out-patient bipolar unit from 1997 to 2007. Binomial statistics was used for the analysis of Hamilton Depression Rating Scale (HDRS)-31 items of the first and second episodes, and the correlation of the HDRS-31 item scores of both episodes was determined using the Spearman coefficient. Ten depressive symptoms showed a significant correlation between index and subsequent episodes: psychological anxiety, somatic anxiety, somatic symptoms, diurnal variation, paranoid symptoms, obsessive and compulsive symptoms, hypersomnia, loss of appetite and helplessness. Only four symptoms were stable in both statistical tests: paranoid symptoms, obsessive-compulsive symptoms, loss of appetite and hypersomnia. Paranoid and obsessive-compulsive symptoms, loss of appetite and hypersomnia tended to be found in successive episodes. However, the moderate correlations of the symptoms across two depressive recurrences suggested that clinical presentations in bipolar depression may not be predicted by symptom profiles presented in previous episodes. [ABSTRACT FROM AUTHOR]

Issler CK, Monkul ES, Amaral JAMS, Tamada RS, Shavitt RG, Miguel EC, Lafer B. Bipolar disorder and comorbid obsessive-compulsive disorder is associated with higher rates of anxiety and impulse control disorders. Objective: Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD. Method: We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking. Results: The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders. Conclusion: Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden. [ABSTRACT FROM AUTHOR]

Objectives: This longitudinal study examined the relationship of Quality of Life (QOL) throughout an 8-year follow-up period with baseline and longitudinal clinical variables indicative of outcome in patients with Bipolar Disorder (BD).Methods: 36 participants, ages 18-70, were recruited from the Bipolar Disorder Research Program (PROMAN) outpatient clinic. Participants completed the WHOQOL-BREF questionnaire in 2009 (baseline), 2015 (6-years) and 2017 (8-years), with high scores being associated with better quality of life. Baseline clinical variables were collected through the Structured Clinical Interview for DSM-IV (SCID-IV) and a structured baseline interview for demographic and clinical assessment. Longitudinal clinical variables were collected through medical records, including mood charts and mood symptoms scales.Results: The results suggest that the QoL, as measured by the WHOQOL-BREF scale, is negatively affected by depressive episodes and is rather stable throughout the course of patients diagnosed with BD. In our study, all three scores were negatively correlated to depressive episodes, and one WHOQOL-BREF score was positively correlated to manic episodes, suggesting that higher scores, both at baseline and throughout the course of the disorder, may be associated to a higher occurrence of manic episodes, while lower QoL scores may be predictive of a higher occurrence of depressive episodes. Also, all three scores revealed significant positive correlations between themselves, suggesting QoL, as measured by the WHOQOL-BREF, remained constant throughout the 8-year observed period. Finally, patients presenting Obsessive Compulsive Disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and substance abuse comorbidities revealed consistent lower WHOQOL-BREF scores, suggesting that these comorbidities may be an important predictor of QoL in BD patients. [ABSTRACT FROM AUTHOR]