Resting State Networks Mediate the Effect of Genotype by Environment Interaction on Mental Health

A number of studies have shown that the presence of short (S) allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with a higher risk for depression following exposure to stressful life events. These findings are in line with neuroimaging studies showing that 5-HTTLPR polymorphism has an effect on the connectivity among key areas involved in emotion regulation. Here using mediated moderation analysis, we show that electrophysiological manifestations of resting state networks in the alpha frequency band mediate the effect of 5-HTTLPR by stress interaction on depression/anxiety symptoms in a nonclinical sample. Specifically, at the brain level, both L-allele homozygotes and S-allele carriers are similarly responsive to stress exposure. However, these brain responses seem to act as triggers of psychopathological symptoms in S-allele carriers, but as suppressors in L-allele homozygotes. This finding implies that the interpretation of the effect of gene by environment interaction on psychopathology seems more complicated than behavioral results alone would imply. It is not just differential sensitivity to stress, but rather different ways of coping with stress, which distinguish S-allele carriers and L-allele homozygotes.