Association of Serotonergic Pathway Gene Polymorphisms With Behavioral Parameters in Patients With Opioid Dependence

Background and aims Opioid dependence is a chronic, relapsing substance use disorder with a multifactorial etiology, including a genetic component. Serotonin pathway gene polymorphisms have been an important focus of research for psychiatric disorders, including substance use disorders. This study aimed to identify the association of serotonin pathway gene polymorphisms with self-harm, depressive symptoms, impulsiveness, and aggression in patients with opioid dependence. Method The study group comprised 366 subjects with opioid dependence and 200 healthy volunteers. Patients were assessed for a history of self-harm, depressive symptoms, impulsiveness, and aggression using standard tools. Genomic DNA was used for genotyping of four polymorphisms - 5-HTTLPR, STin2 VNTR, TPH1 A218C, and TPH2 G703T. Results The short allele of 5-HTTLPR polymorphism showed a significant difference between cases (59.8%) and controls (40.1%) (p=0.001) and revealed an association with age at opioid dependence (p=0.033). There was a borderline significance of the short allele of 5-HTTLPR with the duration of opioid use (p=0.061) and non-plan impulsivity (p=0.076), suggesting a role of 5-HTTLPR in the susceptibility of opioid dependence. The other markers did not differ between cases and controls. However, the STin2A polymorphism revealed a significant association with anger scores, which may indicate its role in aggressive behavior. Conclusions The present study, the first of its kind, suggests an association of 5-HTTLPR polymorphism with opioid dependence and STin2A polymorphism with aggressive behavior among opioid-dependence patients, signifying the role of these markers in our patient population.