A direct test of the diathesis-stress model for depression.

Mol Psychiatry
Authors
Abstract

The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.

Year of Publication
2018
Journal
Mol Psychiatry
Volume
23
Issue
7
Pages
1590-1596
Date Published
2018 Jul
ISSN
1476-5578
DOI
10.1038/mp.2017.130
PubMed ID
28696435
PubMed Central ID
PMC5764823
Links
Grant list
R01 AA007535 / AA / NIAAA NIH HHS / United States
R01 AA013326 / AA / NIAAA NIH HHS / United States
R01 AA013321 / AA / NIAAA NIH HHS / United States
R01 AA010249 / AA / NIAAA NIH HHS / United States
R37 AA007728 / AA / NIAAA NIH HHS / United States