Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene

Abstract

Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.

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

“…31 The two adolescent studies both show an interaction in the expected direction among females only and trend for an opposite effect in males. 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.…”

“…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.…”

“…41 On the other hand, Kendler and colleagues 15 found that a model with recessive s (that is with ll and ls combined) provided best fit to their data and at least one other study showed results consistent with recessive s. 34 Results from child and adolescent samples place heterozygotes intermediate but close to ll homozygotes, suggesting a predominantly recessive s effect for early-onset depression. 30,40,42 When multiple outcomes were considered within one sample, a co-dominant effect was shown for the more common outcome of alcohol abuse, but a recessive s effect was apparent for the less common illicit drug use. 43 In conclusion, the role of 5-HTTLPR heterozygosity in G Â E remains unclear.…”

“…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.…”

“…The studies of G Â E in depression used stressful life events, 11,15,29,32,33,35,43,44 childhood abuse, 11,31,45,34 chronic somatic illness 41 and composite indexes of environmental adversity. 40,42 Moffitt et al 3 specified that a candidate environmental pathogen for G Â E should be a plausible cause of the disorder, proximal to the disorder onset, and have variable effect on different individuals; they further stipulated that cumulative, repeated, or protracted exposures are stronger pathogens than discrete acute events. The stressful life events fit these criteria; childhood abuse is probably not a proximal factor except in childhood depression; composite indexes of adversity are inclusive and cumulative, but it is difficult to date these and establish how close their temporal and aetiological association with the onset of depression is.…”