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.

Factor structure of the Dimensional Yale-Brown Obsessive-Compulsive Scale in a large sample of adults with obsessive-compulsive disorder

Objectives: Although the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) is a widely used instrument for assessing different obsessive-compulsive symptom dimensions, its factor structure has never been studied in a Brazilian population. Thus, we aimed to assess the goodness-of-fit indexes and factor loadings of two higher-order models of the DY-BOCS using confirmatory factor analysis (CFA) in a large obsessive-compulsive disorder (OCD) sample. Methods: We tested two CFA models in a sample of 955 adults with OCD who had been assessed with the DY-BOCS in a cross-sectional multi-site study. The first model encompassed the symptom checklist (present or absent), whereas the second focused on items related to severity scores. Results: Both models presented adequate goodness-of-fit indexes. The comparative fit index, Tucker-Lewis index, and omega were > 0.9, while the root mean square error of approximation was ≤ 0.06 for both models. Factor loadings for each item of each dimension are presented and discussed. Conclusion: Higher-order factor models showed adequate goodness-of-fit indexes, indicating that they appropriately measured OCD dimensions in this Brazilian population.

Predictors of gaming disorder in children and adolescents: a school-based study

Objective: To determine whether psychiatric and gaming pattern variables are associated with gaming disorder in a school-based sample. Methods: We analyzed data from the Brazilian High-Risk Cohort for Psychiatric Disorders, a community sample aged 10 to 18, using questionnaires on gaming use patterns. We applied the Gaming Addiction Scale to diagnose gaming disorder and the Development and Well-Being Behavior Assessment for other diagnoses. Results: Out of 407 subjects, 83 (20.4%) fulfilled the criteria for gaming disorder. More role-playing game players were diagnosed with gaming disorder that any other genre. Gaming disorder rates increased proportionally to the number of genres played. Playing online, being diagnosed with a mental disorder, and more hours of non-stop gaming were associated with higher rates of gaming disorder. When all variables (including age and gender) were considered in a logistic regression model, the number of genres played, the number of non-stop hours, the proportion of online games, and having a diagnosed mental disorder emerged as significant predictors of gaming disorder. Conclusion: Each variable seems to add further risk of gaming disorder among children and adolescents. Monitoring the length of gaming sessions, the number and type of genres played, time spent gaming online, and behavior changes may help parents or guardians identify unhealthy patterns of gaming behavior.

Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

Theoretical models of Obsessive-Compulsive Disorder (OCD): a perspective on future approaches

Obsessive-Compulsive disorder (OCD) is a common psychiatric condition that leads to significant impairment in everyday life. Advancements in neurobiological investigations contributed to a better understanding of pathophysiological mechanisms behind OCD, leading to the understanding that current models employed to conceptualize OCD are not adequate and might be a significant factor in precluding further advancements in how OCD is treated. In this paper, we will use OCD as a model to discuss the limitations of the current diagnostic systems in Psychiatry and to present the novel perspectives based on neurobiological findings that might lead to considerable advancements in treatments for OCD.

No evidence of attentional bias toward angry faces in patients with obsessive-compulsive disorder

Objective: Although attentional bias (AB) toward angry faces is well established in patients with anxiety disorders, it is still poorly studied in obsessive-compulsive disorder (OCD). We investigated whether OCD patients present AB toward angry faces, whether AB is related to symptom severity and whether AB scores are associated with specific OCD symptom dimensions. Method: Forty-eight OCD patients were assessed in clinical evaluations, intelligence testing and a dot-probe AB paradigm that used neutral and angry faces as stimuli. Analyses were performed with a one-sample t-test, Pearson correlations and linear regression. Results: No evidence of AB was observed in OCD patients, nor was there any association between AB and symptom severity or dimension. Psychiatric comorbidity did not affect our results. Conclusion: In accordance with previous studies, we were unable to detect AB in OCD patients. To investigate whether OCD patients have different brain activation patterns from anxiety disorder patients, future studies using a transdiagnostic approach should evaluate AB in OCD and anxiety disorder patients as they perform AB tasks under functional neuroimaging protocols.

Obsessive-compulsive symptoms in children with first degree relatives diagnosed with obsessive-compulsive disorder

Objective: A first-degree relative affected by obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) in childhood is an important risk factor for developing the disorder in adulthood. The relationship between a family history of OCD and the presence of OCS and its correlates in childhood is not well established. Methods: A total of 66 children whose parents or siblings have been diagnosed with OCD were assessed for the presence of OCS and clinical correlates. Results: Three children (4.5%) were reported to have received an OCD diagnosis and another 26 (39.4%) were identified as having OCS. Children with OCS had higher rates of coercive behavior and came from families with lower socioeconomic status. Contamination/cleaning dimension symptoms in the proband were associated with OCS in the assessed children. Conclusion: OCS are frequent among family members of individuals with OCD and are associated with socioeconomic status, coercive behaviors and proband contamination/cleaning symptoms. Future longitudinal studies should test the risk of developing OCD in association with these characteristics.

Prevalence, clinical correlates and maternal psychopathology of deliberate self-harm in children and early adolescents: results from a large community study

Objectives: Little is known about the prevalence and correlates of deliberate self-harm (DSH) in children from low- and middle-income countries. We investigated the prevalence of DSH and its clinical and maternal psychopathological associations in Brazilian children (n=2,508, ages 6-14y) in a community-based study. Methods: Participants of the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders (HRC) and their mothers were assessed in structured interviews. Current (last month) and lifetime DSH were estimated, including analysis stratified by age groups. Logistic regressions were performed to investigate the role of the children's clinical diagnoses and maternal psychopathology on DSH prevalence estimates, adjusting for potential confounding factors. Results: The prevalence of current DSH was 0.8% (children 0.6%, adolescents 1%) and lifetime DSH was 1.6% (1.8% and 1.5%, respectively). Current and lifetime DSH were more frequent in children with depression, attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), even in multiple models accounting for demographic variables and co-occurring psychiatric disorders. Maternal anxiety disorder was strongly associated with current and lifetime DSH in offspring; whereas current DSH, specifically in young children, was associated with maternal mood disorder. Conclusion: Diagnoses of depression, ADHD and ODD were consistently associated with DSH, as was having a mother with anxiety disorder.

Specific and social fears in children and adolescents: separating normative fears from problem indicators and phobias

Objective: To distinguish normative fears from problematic fears and phobias. Methods: We investigated 2,512 children and adolescents from a large community school-based study, the High Risk Study for Psychiatric Disorders. Parent reports of 18 fears and psychiatric diagnosis were investigated. We used two analytical approaches: confirmatory factor analysis (CFA)/item response theory (IRT) and nonparametric receiver operating characteristic (ROC) curve. Results: According to IRT and ROC analyses, social fears are more likely to indicate problems and phobias than specific fears. Most specific fears were normative when mild; all specific fears indicate problems when pervasive. In addition, the situational fear of toilets and people who look unusual were highly indicative of specific phobia. Among social fears, those not restricted to performance and fear of writing in front of others indicate problems when mild. All social fears indicate problems and are highly indicative of social phobia when pervasive. Conclusion: These preliminary findings provide guidance for clinicians and researchers to determine the boundaries that separate normative fears from problem indicators in children and adolescents, and indicate a differential severity threshold for specific and social fears.

Transtorno obsessivo-compulsivo: possíveis subtipos

Several studies suggest that OCD is probably a heterogeneous disorder with several putative subtypes. Differences in treatment response, disease course, and clinical features are suggestive of the existence of subtypes with specific underlying pathophysiological substrates. Whether studying OCD from a phenomenological or genetic standpoint phenotypic characterization becomes crucial. This manuscript summarizes data that support the existence of a subgroup of OCD related to tics, a group with an early age onset; a possible subgroup related to rheumatic fever; and a group with poor insight. Validation of these putative subtypes may be possible with genetic family studies and will contribute to the development of more specific treatments

Transtorno obsessivo-compulsivo resistente: conceito e estratégias de tratamento

Despite the fact that majority of OCD patients responds to conventional treatments, about 40 percent remain symptomatic after appropriate trials with serotonin uptake inhibitors (SRIs) or behavioral therapy. A patient is considered treatment-resistant after failing to respond to three pharmacological trials with SRIs as well as to behavior therapy. When all somatic strategies have been tried, including augmentation with other medications, and the patient remains symptomatic, he or she is considered treatment refractory. The concepts of resistance and refractoriness are briefly revised, and the current augmentation strategies, as well as non-pharmacological approaches such as neurosurgery and transcranial magnetic stimulation, are addressed in this paper. Finally, issues of predictive response factors, pharmacogenetics, and the pathophysiology of resistant cases are suggested as targets for further researches

Marcador D8-17: implicações para a neuropsiquiatria / D8/17 marker: implication to neuropsychiatry

Estudos recentes sugerem uma associação entre febre reumática (FR) e transtornos do espectro obsessivo-compulsivo, o que levou à hipótese de que alterações na resposta imune pudessem ter um papel na etiologia destes últimos. Um marcador biológico que talvez identifique maior susceptibilidade para o desenvolvimento de FR e desses transtornos neuropsiquiátricos tem causado grande interesse na literatura. Trata-se do D8/17, um anticorpo monoclonal contra um antígeno de membrana de linfócitos B. Neste artigo introduzimos conhecimentos sobre o D8/17 e discutimos suas implicações como um possível marcador biológico de transtornos neuropsiquiátricos associados ou não à FR.

Transtorno obsessivo-compulsivo em paciente com sindrome de Tourette e febre reumatica sem coreia de Sydenham

Os autores descrevem um caso inedito de transtorno obsessivo-compulsivo (TOC) em paciente com sindrome de Tourette (ST) e febre reumatica (FR) sem coreia de Sydenham (CS), com inicio dos tiques no comeco da infancia. Discutem os possiveis mecanismos fisiopatologicos implicados nessa associacao