Sociocultural stress and SLC6A4 gene polymorphism contribute to telomere shortening in depression

Abstract Telomeres shorten due to environmental and psychological stress. Psychiatric disorders, especially those triggered by stress, can alter telomere length. Genetic factors associated with depression vary across cultures and environments. The serotonin-transporter-linked polymorphic region (5-HTTLPR) of SLC6A4 has been associated with susceptibility to depression, but the risk allele appears to differ between populations. This study aimed to investigate the correlation between telomere length and depression in Indonesia, focusing on socioeconomic, cultural, and genetic factors amidst rapid social changes. We recruited 97 psychiatric outpatients and 101 participants without depressive symptoms. Psychological assessments were conducted using the Self-Construal Scale (SCS) and Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) via interviews. DNA extracted from the peripheral blood was used to identify the SLC6A4 genotype by PCR, and telomere length was measured by quantitative PCR. The comparison of patients with depression and controls revealed significant telomere shortening in the patient group ( p < 0.0001, Mann-Whitney U-test). Logistic regression showed that psychological scales were stronger predictors of depression than telomere length or SLC6A4 polymorphisms. A multiple regression analysis indicated that the LL genotype of SLC6A4 , but not socioeconomic or psychological factors, was strongly associated with telomere length ( p = 0.001). This study is the first to analyze both psychological and genetic factors in the relationship between depression and telomere shortening, providing new insights into the genetic co-evolution mechanisms associated with depression.