The Interaction of Stressful Life Events and a Serotonin Transporter Polymorphism in the Prediction of Episodes of Major Depression

Abstract

Variation at the 5-HTT moderates the sensitivity of individuals to the depressogenic effects of SLEs largely by producing, in SS individuals, an increased sensitivity to the impact of mild stressors. Replication of these intriguing results is needed.

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

“…Even in a study where positive results were reported separately for both genders, the G Â E was stronger in females. 15 Of the four studies with predominantly middle-aged to elderly samples, two showed no evidence of interaction with the non-significant interaction signs pointing in the opposite direction; 44,45 one identified an interaction in the expected direction for female participants only, 41 and one in the whole sample after correcting for gender. 32 The observed pattern of variation by age and gender is likely to reflect several interacting factors.…”

“…Prospective cohort study design has been used in seven studies; 11,15,29,[42][43][44] although these studies were prospective in nature and included repeated assessments, the depression and SLE were typically assessed at the same time point, leaving the possibility that recall of SLEs may be influenced by the depressed state. 48 Six studies were cross-sectional surveys.…”

“…40,42 The G Â E interaction is consistently positive in young adults. 11,15,29,33,35 Note that in the study of Mandelli and colleagues 33 the middle-aged participants are retrospectively interviewed about events preceding their first affective episode, which occurred on average in their early 30s. Even in a study where positive results were reported separately for both genders, the G Â E was stronger in females.…”

“…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.…”

“…[4][5][6][7] In the last five years, G Â E involving specific gene polymorphisms has been identified in animals 8,9 and humans. [10][11][12][13] Encouragingly, replications 14,15 and a positive metaanalysis 16 indicate that measuring environment improves the reliability of genetic research.…”