GENETICS OF OBSESSIVE-COMPULSIVE DISORDER

Abstract

Obsessive-compulsive disorder (OCD) is characterized by recurrent episodes of obsessive thoughts, fears, and actions, which, in the opinion of the patient, can defuse frightening events. A patient himself is aware of his condition, but cannot prevent it by a simple effort of will. The prevalence of OCD in the general population varies between 0.7% and 3.0%. Patients with OCD often can have a lifetime diagnosis of other psychopathology – an anxiety disorder, depressive disorder, tic disorder and others. In addition, the OCD symptoms often accompany other mental disorders, such as schizophrenia, bipolar disorder, eating disorder and others.
 Family studies in OCD showed that the disorder risk of first-degree relatives of individuals with OCD were approximately 15%, that more likely to develop OCD than its prevalence in the general population. This indicates the presence of a genetic component in the OCD development, that is also confirmed by the significant reliable value of the heritability of OCD (42-53%). Males have an earlier age at onset of OCD than females. Moreover, males more likely to have symptoms in the forbidden thoughts and symmetry dimensions and females more likely to have symptoms in the cleaning dimension. In addition, geographical and cultural factors may shape the content of obsessions and compulsions.
 There are four publications that have shown OCD genetic linkage with defined regions of three chromosomes: 9p24, 3q27-28 and 14q23-32. It was also found that the region of chromosome 3q27-28 contains three genes of serotonin receptor subunits – HTR3C (5HT3C), HTR3D (5HT3D) and HTR3E (5HT3E). These genes can be candidate genes for OCD. In addition, the HTR3C gene (3q27.1) is expressed in the brain cells, where it produces the serotonin receptor 3 subunit, which is a very important neurotransmitter. All three genes involved in the pathogenesis of not only OCD, but also of schizophrenia.
 Now, according to scientific reviews and «MalaCard: The Human Disease Database» above 40 OCD candidate genes were offered by various researchers. But almost all these studies were conducted on statistically insignificant samples (mostly from several dozens to several hundred individuals), which gave discrepant findings. In addition, not fully used methodological possibilities, for example, case-control samples were used, but family studies were not used. For this reason, the Canadian researcher S. Taylor (2013) conducted a meta-analysis of the findings of 113 studies and obtained high reliable confirmation of an assumption that variants of several genes are involved in the risk of OCD. Two of these genes associated with metabolism of serotonin (SLC6A4 and HTR2A) and two genes, in males only, are involved in catecholamine modulation (COMT and MAOA). Some more three genes have moderate reliability, two of which are associated with the dopamine system (DRD3 and DAT1) and one is associated with the glutamate system (SLC1A1). In addition, in S. Taylor’s opinion, 13 candidate genes attract an attention and merit further investigation.
 The results of genetic studies showed that OCD has a polygenic nature, because it is associated with multiple genes, everyone of them makes small contributions to a risk for the disorder. To reveal of these small effects, further studies of fairly large samples are needed. In addition, environmental factors may be involved in the OCD etiology that further exploration of gene–gene and gene–environment interactions is needed. To identify reliable OCD candidate genes all comorbidities must take into account. The OCD picture is extremely various not only in a lifetime of one patient, but between patients within the same family that indicates genetic heterogeneity of the disorder, which complicates the study in addition. These problems induce to study the genetic nature and environmental risk factors of OCD to ensure an earliest and most accurate diagnosis of OCD with due regard for environmental factors.