Stefan Wüst

Genetic factors contribute significantly to interindividual differences in the susceptibility to stress‐related disorders. As stress can also be conceptualized as environmental exposure, controlled gene–environment interaction (GxE) studies with an in‐depth phenotyping may help to unravel mechanisms underlying the interplay between genetic factors and stress. In a prospective‐longitudinal quasi‐experimental study, we investigated whether polygenic scores (PGS) for depression (DEP‐PGS) and neuroticism (NEU‐PGS), respectively, were associated with responses to chronic stress in daily life. We examined law students ( n = 432) over 13 months. Participants in the stress group experienced a long‐lasting stress phase, namely the preparation for the first state examination for law students. The control group consisted of law students without particular stress exposure. In the present manuscript, we analyzed perceived stress levels assessed at high frequency and in an ecologically valid manner by ambulatory assessments as well as depression symptoms and two parameters of the cortisol awakening response. The latter was only assessed in a subsample ( n = 196). No associations between the DEP‐PGS and stress‐related variables were found. However, for the NEU‐PGS we found a significant GxE effect. Only in individuals experiencing academic stress a higher PGS for neuroticism predicted stronger increases of perceived stress levels until the exam. At baseline, a higher NEU‐PGS was associated with higher perceived stress levels in both groups. Despite the small sample size, we provide preliminary evidence that the genetic disposition for neuroticism is associated with stress level increases in daily life during a long‐lasting stress period.

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task‐based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm Scan STRESS . Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex‐specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18–33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex‐specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato‐limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation‐ and context‐dependent reactions of the limbic system (i.e. blood oxygenation level‐dependent reactions) are related to acute (sex‐specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic.