Irritable Personality Trait and Type of Antidepressant Prescribed Moderates the Association between genotypes of HTR1A-rs6295 or HTR2A-rs6311 with Treatment Response.

Abstract

Background Currently, empiric treatment of major depressive disorder (MDD) relies on the characteristics of the presenting patients. Aim The aim of the current study was to identify moderators for the association of SSRI treatment efficacy response phenotype with genotypes of HTR1A-rs6295 or HTR2A-rs6311 polymorphism in a population of MDD patients. Methodology The study included 300 patients with MDD. The assessment of selective serotonin reuptake inhibitors (SSRI) treatment response was based on 50% reduction in the depressive score obtained within 6 weeks of treatment onset on the Montgomery asberg depression rating scale (MADRS-S) for each patient recruited in the psychiatric clinics of the four tertiary hospitals in the Klang valley region of Malaysia. Result The study population was made up of young adults (median age = 37.00years), mostly females (67.1%) with no family history of psychiatric illness (73.4%). MDD patients with the GA genotype for the HTR2A-rs6311 polymorphism and received escitalopram antidepressant were significantly (over-dominant model; P = 0.019, OR = 0.114 (0.019–0.701)) less likely to respond to treatment. The CG + GG genotype of HTR1A-rs6295 gene polymorphism was associated with significantly (recessive model: P = 0.019, OR = 0.146 (0.026–0.733)) reduced likelihood of responding to antidepressant treatment among the MDD patients with the irritability personality trait. Conclusion The association between the CG genotype of the HTR1A-rs6295 with poor SSRI treatment response is elaborated among patients that have an irritable personality. The role of medication type in determining the direction of association between genotype of the HTR2A-rs6311 with treatment response identified in the literature was also revalidated in the current study.