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.

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.

Randomized, Double-Blind, Placebo-Controlled Trial of N-Acetylcysteine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder.

OBJECTIVE: To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). METHODS: We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014). The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. To evaluate the variables group, time, and interaction effects for Y-BOCS scores at all time points, we used nonparametric analysis of variance with repeated measures. Secondary outcomes were the severity scores for anxiety, depression, specific OCD symptom dimensions, and insight. RESULTS: Both groups showed a significant reduction of baseline Y-BOCS scores at week 16: the NAC group had a reduction of 4.3 points (25.6 to 21.3), compared with 3.0 points (24.8 to 21.8) for the placebo group. However, there were no significant differences between groups (P = .92). Adding NAC was superior to placebo in reducing anxiety symptoms (P = .02), but not depression severity or specific OCD symptom dimensions. In general, NAC was well tolerated, despite abdominal pain being more frequently reported in the NAC group (n [%]: NAC = 9 [60.0], placebo = 2 [13.3]; P < .01). CONCLUSIONS: Our trial did not demonstrate a significant benefit of NAC in reducing OCD severity in treatment-resistant OCD adults. Secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms in treatment-resistant OCD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01555970.

Dissecting the Yale-Brown Obsessive-Compulsive Scale severity scale to understand the routes for symptomatic improvement in obsessive-compulsive disorder.

We aimed to investigate which items of the Yale-Brown Obsessive-Compulsive Severity Scale best discriminate the reduction in total scores in obsessive-compulsive disorder patients after 4 and 12 weeks of pharmacological treatment. Data from 112 obsessive-compulsive disorder patients who received fluoxetine (⩽80 mg/day) for 12 weeks were included. Improvement indices were built for each Yale-Brown Obsessive-Compulsive Severity Scale item at two timeframes: from baseline to week 4 and from baseline to week 12. Indices for each item were correlated with the total scores for obsessions and compulsions and then ranked by correlation coefficient. A correlation coefficient ⩾0.7 was used to identify items that contributed significantly to reducing obsessive-compulsive disorder severity. At week 4, the distress items reached the threshold of 0.7 for improvement on the obsession and compulsion subscales although, contrary to our expectations, there was greater improvement in the control items than in the distress items. At week 12, there was greater improvement in the time, interference, and control items than in the distress items. The use of fluoxetine led first to reductions in distress and increases in control over symptoms before affecting the time spent on, and interference from, obsessions and compulsions. Resistance did not correlate with overall improvement. Understanding the pathway of improvement with pharmacological treatment in obsessive-compulsive disorder may provide clues about how to optimize the effects of medication.

Phenomenology of OCD: lessons from a large multicenter study and implications for ICD-11.

This study aimed to investigate the phenomenology of obsessive-compulsive disorder (OCD), addressing specific questions about the nature of obsessions and compulsions, and to contribute to the World Health Organization's (WHO) revision of OCD diagnostic guidelines. Data from 1001 patients from the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders were used. Patients were evaluated by trained clinicians using validated instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale, the University of Sao Paulo Sensory Phenomena Scale, and the Brown Assessment of Beliefs Scale. The aims were to compare the types of sensory phenomena (SP, subjective experiences that precede or accompany compulsions) in OCD patients with and without tic disorders and to determine the frequency of mental compulsions, the co-occurrence of obsessions and compulsions, and the range of insight. SP were common in the whole sample, but patients with tic disorders were more likely to have physical sensations and urges only. Mental compulsions occurred in the majority of OCD patients. It was extremely rare for OCD patients to have obsessions without compulsions. A wide range of insight into OCD beliefs was observed, with a small subset presenting no insight. The data generated from this large sample will help practicing clinicians appreciate the full range of OCD symptoms and confirm prior studies in smaller samples the degree to which insight varies. These findings also support specific revisions to the WHO's diagnostic guidelines for OCD, such as describing sensory phenomena, mental compulsions and level of insight, so that the world-wide recognition of this disabling disorder is increased.

Panic Disorder and Agoraphobia in OCD patients: clinical profile and possible treatment implications.

OBJECTIVE: Panic Disorder (PD) and agoraphobia (AG) are frequently comorbid with obsessive-compulsive disorder (OCD), but the correlates of these comorbidities in OCD are fairly unknown. The study aims were to: 1) estimate the prevalence of PD with or without AG (PD), AG without panic (AG) and PD and/or AG (PD/AG) in a large clinical sample of OCD patients and 2) compare the characteristics of individuals with and without these comorbid conditions. METHOD: A cross-sectional study with 1001 patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders using several assessment instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Bivariate analyses were followed by logistic regression models. RESULTS: The lifetime prevalence of PD was 15.3% (N=153), of AG 4.9% (N=49), and of PD/AG 20.2% (N=202). After logistic regression, hypochondriasis and specific phobia were common correlates of the three study groups. PD comorbidity was also associated with higher levels of anxiety, having children, major depression, bipolar I, generalized anxiety and posttraumatic stress disorders. Other independent correlates of AG were: dysthymia, bipolar II disorder, social phobia, impulsive-compulsive internet use, bulimia nervosa and binge eating disorder. Patients with PD/AG were also more likely to be married and to present high anxiety, separation anxiety disorder, major depression, impulsive-compulsive internet use, generalized anxiety, posttraumatic stress and binge eating disorders. CONCLUSIONS: Some distinct correlates were obtained for PD and AG in OCD patients, indicating the need for more specific and tailored treatment strategies for individuals with each of these clinical profiles.