A direct test of the diathesis–stress model for depression

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 5 221 individuals from 3 083 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.

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study

“…But, it is also consistent with recent work demonstrating increased heritability of perinatal mood disorders in particular (Viktorin et al, 2016). Consequently, the growing literature on using polygenic risk scores to con- Colodro-Conde et al, 2017). Therefore, while parental psychopathology serves as marker for a genetic vulnerability to psychiatric disorders and depression in general, it is also an important marker of environmental stress for the individual girl who likely was raised in a more stressful environment.…”

Is it worth turning a trigger into a joke? Humor as an emotion regulation strategy in remitted depression

“…Depression is a highly recurrent mental disorder, with about 75% of recovered people having more additional episodes in their lifetime (Richards, 2011). According to the diathesis-stress approach (see Colodro-Conde et al, 2018), depressive episodes develop as a result of an interaction between negative life events and individuals' vulnerability to depression. When the vulnerability is high, which especially pertains to recurrent depressive disorder, the negative events required to trigger depression are typically less serious.…”

Incorporating polygenic scores in the twin model to estimate genotype-environment covariance: exploration of statistical power

“…While we have focused on covariance, we note that polygenic scores have wider applications in the study of genotype-environment interplay. Polygenic scores are already being used to study interaction (e.g., Colodro-Conde et al 2018;Peyrot, et al 2014). Assigning polygenic scores the role of moderator in the twin moderation model (Purcell, 2002) will facilitate the study of AxE and AxC interaction, allowing for the developmentally important distinction of AxC and AxE.…”