Association of a Triallelic Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism With Stressful Life Events and Severity of Depression

Abstract

Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

“…38 Two studies used casesonly design to investigate the association of SLE preceding the onset of depression with genotype 49 or the interaction of SLE during the course of the disorder with genotype on current symptom severity. 36 There is no obvious association between study design and results.…”

“…51 Serotonin transporter gene-environment interactionunselected primary care attendees, 37 three studies used convenience samples of students or teachers; 34,35,43 three studies used enriched samples selected based on experience of childhood abuse, 31 high levels of social adversity and depression 40 or extremes on neuroticism 45 and two studies used clinical samples of depressed patients. 33,36 Sample size is a major determinant of power to detect G Â E. 52 It is therefore notable that the two studies with largest samples produced negative findings. 44,45 However, both of these samples were recruited and assessed for reasons other than depression research: their primary aims were study of cancer 45 or addiction 44 and the assessment procedures were not designed for the study of depression and SLEs.…”

“…Taken at face value, there were eleven replications, 15,[29][30][31][32][33][34][35][36][37][38][39] three partial replications in females only, [40][41][42] and three non-replications. [43][44][45] Importantly, two studies with very large samples were negative.…”

“…36 However, it is presently unknown whether the in vitro transcriptional activity differences are responsible for the G Â E interaction observed at the population level. We suggest that the two models are compared in future investigations; if the reported in vitro functionality determines the G Â E, the specification of L A and L G alleles should improve model fit.…”

“…126,136 However, the only way to obviate the retrospective recall bias is to obtain an objective record of the SLE. 137 Of the reviewed studies, five used structured interviews, 11,15,33,35,36 one used semistructured interview, 42 nine used questionnaires 29,32,34,37,40,41,[43][44][45] and one used objective record of child abuse. 31 All studies that used a structured interview to assess SLEs have found a G Â E with the 5-HTTLPR s allele.…”