Life stress, 5-HTTLPR and mental disorder: findings from a 30-year longitudinal study

Background Recent meta-analyses have raised concerns about the replicability of gene x environment interactions involving the serotonin transporter gene (5-HTTLPR) in moderating the associations between adverse life events and mental disorders. Aims To use data gathered over the course of a 30-year longitudinal study of a New Zealand birth cohort to test the hypothesis that the presence of short ('s') alleles of 5-HTTLPR are associated with an increased response to life stress. Method Participants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events. Results A series of 104 regression models were fitted to four mental health outcomes (depressive symptoms, major depression, anxiety disorder and suicidal ideation) observed at ages 18, 21, 25 and 30 using 13 measures of life-course stress that spanned childhood and adult stressors. Both multiplicative and additive models were fitted to the data. No evidence was found that would support the hypothesis that alleles of 5-HTTLPR are associated with increased responsivity to life stressors. Conclusions The present findings add to the evidence suggesting that it is unlikely that there is a stable gene x environment interaction involving 5-HTTLPR, life stress and mental disorders.