SU71 - BDNF GENE AND OBSESSIVE COMPULSIVE DISORDER – DO SYMPTOM DIMENSIONS HAVE SPECIFIC GENETIC CORRELATES?

Abstract

Background Obsessive Compulsive Disorder (OCD) is a common neuropsychiatric disorder with a worldwide 12-month prevalence ranging from 1% to 2% across studies (Weissman et al., 1995; Ruscio et al., 2010). Characterized by repetitive intrusive thoughts, images and impulses (obsessions) and repetitive behaviors or mental acts (compulsions), the clinical phenotype of OCD appears to be complex. Genetic etiology of Obsessive Compulsive Disorder (OCD) has been investigated extensively, with mixed results across candidate gene studies. In this study, we perform a case control analysis of association of a single nucleotide polymorphism rs6265(Val66Met) in Brain Derived Neurotrophic Factor gene, that has been previously implicated in a variety of psychiatric syndromes, and examine its association with symptom dimensions of OCD. Methods Patients (n=377) diagnosed with OCD by DSM IV – TR were recruited from a specialty OCD clinic at the NIMHANS, Bengaluru, INDIA. Patients were assessed on socio-demographic data, detailed history of illness, presence of common co-morbid disorders, family history of OCD and major psychiatric disorders, and treatment details. Patients were additionally assessed on Yale Brown Obsessive Compulsive Scale (YBOCS), Mini International Neuropsychiatric Interview plus (MINI plus) Clinical Global Impression scale (CGI). Control population (n=449) consisted of healthy individuals also of south Indian origin. MINI plus was administered to screen and rule out psychiatric diagnosis in this group. DNA samples were genotyped for polymorphism rs6265 (Val66Met) using Quantitative Real time PCR. Results Factor analysis yielded five factor solutions as the best fit for the data explaining 65% of the variance as follows - Factor-1 with robust loading on hoarding obsession (0.891) & collecting compulsions (0.913). Factor-2 with Obsessions of need for symmetry (0.821) & ordering compulsions (0.864). Factor-3 with Pathological doubts obsessions (0.824) & checking compulsions (0.819). Factor-4 with Sexual (0.680), religious (0.655) &aggressive obsessions (0.554), mental rituals compulsions (0.630) and Factor-5 with Contamination obsessions (0.919) & washing compulsions (0.893). The allele ‘A’ frequency was found to be significantly higher in the controls, as compared to cases suggesting a protective effect. Among the clinical variables tested in univariate analysis by genotype, factor-5 (contamination obsessions with washing compulsions) and factor 1 (hoarding), dimension scores was significantly lower in ‘A’ carriers in subjects with OCD compared to homozygous G carriers (GG). Discussion Our findings suggest a protective effect of the rarer Met allele in OCD. The lower factor-5 scores in Met carrier patients and its confirmation after controlling for the confounders further suggests a probable specific protective effect in contamination-washing dimension of OCD. This dimension, which is one of the most commonly observed clinical phenotype, may represent a more homogenous group, with specific biological underpinnings. Functional imaging studies show that the same sub-group of OCD patients demonstrate specific regional activation in ventromedial prefrontal regions in symptom provocation paradigm (Mataix-Cols et al., 2004). The Met allele of rs6265 has also been associated with volumetric reduction in the same region (Yu et al., 2009). These findings suggest a need for future imaging and genetic studies in specific symptom dimensions of OCD.