Examination of gene polymorphisms of serotonergic, dopaminergic and glutamatergic mechanisms in terms of impulsivity in patients diagnosed with obsessive-compulsive disorder (OCD)

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition characterized by persistent, intrusive thoughts and the engagement in repetitive behaviors or rituals intended to mitigate these thoughts. OCD frequently co-occurs with other psychiatric disorders, notably anxiety and depression. A significant limitation of the numerous genetic association studies conducted over the past decade, which have explored candidate genes potentially involved in the pathophysiology and pharmacology of OCD, is their identification of only a limited number of serotonergic, dopaminergic, and glutamatergic polymorphisms. These studies have not sufficiently addressed the potential combined effects of neurotransmitter systems on OCD and impulsivity. This thesis investigates the gene polymorphisms of serotonergic (SCL6A4 and HTR2A), dopaminergic (DRD2/ANKK1 and SLC6A3), and glutamatergic (SLC1A1) mechanisms, which are currently studied in the literature as candidate genes for OCD. DNA profiling was performed following DNA isolation from oral swab samples, using a Real-Time PCR protocol. The study sample consisted of two groups: patients (n=204) and controls (n=100), aged between 18 and 70 years. Although the association between OCD and impulsivity is not yet formally recognized, there is ongoing discussion that impulsivity may be a characteristic of OCD. In this study, Barratt Impulsiveness Scale (BIS-11) scores were statistically analyzed according to different allele distributions for five genetic regions. Significant differences were found between patient and control groups in terms of BIS-11 scores across different allele groups, covering attention, motor, non-planning subscales, and total score. This suggests that variations in these specific genetic regions significantly impacted impulsivity levels as measured by the BIS-11 in this sample. Genetic comparisons of impulsivity scores revealed significant differences in certain alleles of OCD patients. Notably, the CC allele in the SLC6A4 gene exhibited a significant difference compared to the control group. In the HTR2A gene, the CT polymorphism was significant in OCD patients. The AA and AG polymorphisms in the ANKK1 gene were highly significant among OCD patients. Additionally, the CC polymorphism in the SLC6A3 gene was significantly different in OCD patients compared to the control group. In the SLC1A1 gene region, the GG allele showed a significant difference between OCD patients and the control group. This study represents the first comprehensive investigation conducted in Türkiye on a population-specific basis, integrating psychiatric and genetic aspects of OCD and examining its relationship with impulsivity within the context of forensic sciences. The findings aim to evaluate the potential risks and statuses of individuals within the same population pool, contributing to a deeper understanding of OCD's genetic underpinnings and its behavioral manifestations.