Attentional Bias in specific symmetry and cleaning dimensions of obsessive-compulsive disorder.

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.

Quantifying dimensional severity of obsessive-compulsive disorder for neurobiological research.

Current research to explore genetic susceptibility factors in obsessive-compulsive disorder (OCD) has resulted in the tentative identification of a small number of genes. However, findings have not been readily replicated. It is now broadly accepted that a major limitation to this work is the heterogeneous nature of this disorder, and that an approach incorporating OCD symptom dimensions in a quantitative manner may be more successful in identifying both common as well as dimension-specific vulnerability genetic factors. As most existing genetic datasets did not collect specific dimensional severity ratings, a specific method to reliably extract dimensional ratings from the most widely used severity rating scale, the Yale-Brown Obsessive Compulsive Scale (YBOCS), for OCD is needed. This project aims to develop and validate a novel algorithm to extrapolate specific dimensional symptom severity ratings in OCD from the existing YBOCS for use in genetics and other neurobiological research. To accomplish this goal, we used a large data set comprising adult subjects from three independent sites: the Brazilian OCD Consortium, the Sunnybrook Health Sciences Centre in Toronto, Canada and the Hospital of Bellvitge, in Barcelona, Spain. A multinomial logistic regression was proposed to model and predict the quantitative phenotype [i.e., the severity of each of the five homogeneous symptom dimensions of the Dimensional YBOCS (DYBOCS)] in subjects who have only YBOCS (categorical) data. YBOCS and DYBOCS data obtained from 1183 subjects were used to build the model, which was tested with the leave-one-out cross-validation method. The model's goodness of fit, accepting a deviation of up to three points in the predicted DYBOCS score, varied from 78% (symmetry/order) to 84% (cleaning/contamination and hoarding dimensions). These results suggest that this algorithm may be a valuable tool for extracting dimensional phenotypic data for neurobiological studies in OCD.

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design. METHODS: Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed. RESULTS: OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A. CONCLUSIONS: The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos / The role of the VNTR functional polymorphism of the promoter region of the MAOA gene on psychiatric disorders

INTRODUÇÃO: Muitos estudos têm investigado a associação do polimorfismo VNTR (número variável de repetições em série) localizado na região promotora do gene da enzima monoamina oxidase A (MAOA) com alterações no comportamento humano e em diversos transtornos psiquiátricos. OBJETIVO: O objetivo do presente trabalho foi revisar a literatura sobre a participação desse polimorfismo funcional na modulação do comportamento humano para o desenvolvimento dos transtornos psiquiátricos. MÉTODO: A pesquisa foi realizada na literatura em inglês, de janeiro de 1998 a junho de 2009, disponível no Medline, Embase, Web of Science e na base de dados PsycInfo, utilizando os seguintes termos: "MAOA e comportamento humano" e "MAOA e psiquiatria". RESULTADOS: Foram encontrados 3.873 estudos. Desses, 109 foram selecionados e incluídos na revisão. Encontrou-se associação de alelos de baixa atividade do VNTR com transtorno de personalidade antissocial, transtorno de conduta, transtorno de déficit de atenção e hiperatividade, jogo patológico e dependência de substâncias. Alelos da alta atividade da MAOA foram associados a depressão, ansiedade, neuroticismo e anorexia nervosa. Não se encontrou associação entre polimorfismos da MAOA e esquizofrenia e transtorno bipolar. CONCLUSÃO: Os principais achados dão suporte ao papel do polimorfismo VNTR da região promotora do gene da MAOA em alguns transtornos psiquiátricos, apesar das divergências encontradas devidas às dificuldades metodológicas de estudos em genética. De modo geral, os estudos associam os alelos de baixa atividade da MAOA com comportamentos impulsivos e agressivos ("comportamentos hiperativos"), enquanto os alelos de alta atividade do gene são mais associados a "comportamentos hipoativos".

INTRODUCTION: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. OBJECTIVE: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. METHOD: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". RESULTS: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. DISCUSSION: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.