Abstract
Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4919 individuals. We identified nominally significant positive GxE effects in the full cohort (R2 = 0.08%, p = 0.049) and in women (R2 = 0.19%, p = 0.017), but not in men (R2 = 0.15%, p = 0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R2 = 0.15%, p = 0.038; R2 = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10−4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (β = 0.082, p = 0.016) but had a protective effect in women (β = −0.061, p = 0.037). This difference was nominally significant (p = 0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.
Highlights
Stressful life events (SLE) have been consistently recognized as a determinant of depressive symptoms, with many studies reporting significant associations between SLE and major depressive disorder (MDD)[1,2,3,4,5,6,7]
The variance in depression score explained by the total number of SLE (TSLE) appeared to be lower than the variance explained by the measure of personal SLE (PSLE) used in ColodroConde et al.[23] (12.9%)
Questions about dependent SLE (DSLE, mean = 0.4 SLE) represented over 28% of the TSLE-items reported in our study, the main effect of DSLE explained approximately 93% of the amount of variance explained by TSLE
Summary
Stressful life events (SLE) have been consistently recognized as a determinant of depressive symptoms, with many studies reporting significant associations between SLE and major depressive disorder (MDD)[1,2,3,4,5,6,7]. Some individuals facing severe stress never present symptoms of depression[10] This has led to a suggestion that the interaction between stress and an individual’s vulnerability, or diathesis, is a key element in the development of depressive symptoms. Such vulnerability can be conceived as a set of biological factors that predispose to illness. Several diathesis-stress models have been successfully applied across many psychopathologies[11,12,13,14,15]
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