A relationship between early life stress and depression: the role of the serotonin transporter gene polymorphism (5-HTTLPR)

Abstract

Early life stress has been associated with many different negative outcomes including adulthood depression. Studies have suggested a role of the serotonin transporter gene polymorphism (5-HTTLPR) in explaining this relationship. However, consistent replication of this gene-environment interaction have proven difficult. This paper will review contrasting evidence assessing this interaction. Previous research has revealed a complex interplay of factors that might explain how certain 5-HTTLPR genotypes interact with early life stress to produce sensitivity to stress and adulthood depression. Maladaptive cognitive and behavioral patterns will be reviewed in light of 5-HTTLPR's impact on brain regions associated with mood regulation. Future research directions and clinical interventions will also be discussed.

Clinical Utilization of Pharmacogenetics in Psychiatry – Perspectives of Pharmacists, Genetic Counselors, Implementation Science, Clinicians, and Industry

“…Some multigene PGx testing panels may include genes with variants that lead to increased susceptibility to disease that may warrant a referral to a genetic counselor. For example, patients undergoing PGx testing for mental health or treatment may also find out that they are a carrier of SLC6A4, which is often included on psychiatric PGx tests related to response and side effects with SSRIs, but some studies have also implicated the variants in susceptibility to depression, especially in the presence of early life stress [79]. CPIC guidelines include a section dedicated to the investigation of these ancillary findings and is a starting point for counseling patients, but it is not an exhaustive list.…”

“Out, out, brief candle! Life’s but a walking shadow”: 5-HTTLPR Is Associated With Current Suicidal Ideation but Not With Previous Suicide Attempts and Interacts With Recent Relationship Problems

“…In the initial report concerning the role of the 5-HTTLPR s allele in increasing sensitivity towards recent stressors and thus increasing the risk of depression, as well as suicidal ideation and attempts, in the face of stress exposure ( 22 ), a significant interaction between early childhood trauma during the first 10 years and 5-HTTLPR genotype in predicting depression (but not suicide) has also been shown. Later it has been hypothesized that 5-HTTLPR mainly mediates effects of early childhood stressors impacting neurodevelopment, leading to altered brain functioning in regions involved in mood and emotion regulation and consequentially maladaptive cognitive and behavioral patterns contributing to the manifestation of depression and risk of suicide ( 57 , 58 ). While a few studies specifically looked at the interactions between early childhood stressors and 5-HTTLPR on risk of suicidal behaviors, results have been conflicting.…”