Genome-wide stress sensitivity moderates the stress-depression relationship in a nationally representative sample of adults

Abstract

We re-evaluate the findings of one of the most cited and disputed papers in gene-environment interaction (GxE) literature. In 2003, a paper was published in Science in which the authors demonstrated that the relationship between stress and depression is moderated by a polymorphism in the promoter region (5-HTTLPR) of the gene SLC6A4. Replication has been weak and led many to challenge the overall significance of GxE research. Here, we utilize data from Add Health, a large, nationally representative, and well-powered longitudinal study to re-examine the genetic determinants of stress sensitivity. We characterize environmental sensitivity using a genome-wide polygenic indicator rather than relying on one polymorphism in a single candidate gene. Our results provide support for the stress-diathesis perspective and validate the scientific contributions of the original paper.

Sensory Processing Sensitivity and Gastrointestinal Symptoms in Japanese Adults

“…Susceptibility to environmental influences is not a binary variable, but a continuous variable with an assumed normal distribution, ranging from low to high [ 4 ]. According to several prevailing theories [ 5 , 6 ], the interaction between susceptibility genes [ 7 ] and the early environment (both supportive and adversarial) [ 8 ] shapes the susceptibility of the central nervous system. When highly sensitive individuals are exposed to certain environmental stimuli, an increase in neurophysiological reactivity is observed (e.g., activation of the amygdala and insular cortex; [ 9 ]), along with behaviors exhibiting heightened sensitivity (e.g., difficult temperament; [ 10 ]).…”

Genetic sensitivity predicts long-term psychological benefits of a relationship education program for married couples.

“…Evidence of the validity of the polygenic plasticity index emerged from research showing it moderated effects of observed parenting quality on children’s emotional development (Keers et al, 2016), explained variation in the efficacy of different types of Cognitive Behavioral Therapy (CBT) for child anxiety disorders (Keers et al, 2016), and explained variation in effects of a family intervention on children’s internalizing symptoms (Lemery-Chalfant et al, 2018). Most recently, the same polygenic score accounted for variability in effects of stressful life events on adults’ depression symptoms (Davidson et al, 2021).…”

Sensory Processing Sensitivity and Gastrointestinal Symptoms in Japanese Adult

“…Susceptibility to environmental influences is not a binary variable, but a continuous variable with an assumed normal distribution, ranging from low to high (e.g., Zhang et al, 2021). According to several prevailing theories (e.g., Boyce & Ellis, 2005;Belsky & Pluess, 2009), the interaction between susceptibility genes (Davidson et al, 2021) and the early environment (both supportive and adversarial) (Shakiba et al, 2020) shapes the susceptibility of the central nervous system. When highly sensitive individuals are exposed to certain environmental stimuli, an increase in neurophysiological reactivity is observed (e.g., activation of the amygdala and insular cortex; Acevedo et al, 2014) along with behaviors exhibiting heightened sensitivity (e.g., difficult temperament; Pluess & Belsky, 2011).…”