Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population

Abstract

Purpose Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder. Methods A total of 148 depressive patients receiving escitalopram 10–20 mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student’s t test or one-way ANOVA. Results Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, L_AL_A haplotypes, and 2 L_A functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous L_A carriers compared with other groups. Conclusion Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and L_AL_A haplotypes being the predictors of better treatment response.