Social stress, cortisol awakening response and sex: association with hippocampus and amygdala volume.

OBJECTIVE: Volumes of the hippocampus and amygdala, both major hubs for neural stress regulation amongst others, are associated with social stressors, cortisol awakening response (CAR) and sex. Importantly, the interplay of these different factors in affecting the morphology of both brain regions remains unclear. This study aimed to elucidate the intricate influence of these factors on grey matter volumes (GMV) of the hippocampus and amygdala. METHODS: We analyzed associations between structural brain data, self-reported chronic social stress (including subscales on social tension, social overload, lack of social recognition and social isolation) and CAR of 83 healthy participants (40 females) with multiple regression analyses. RESULTS: In males, but not females, higher levels of social tension were associated with lower bilateral hippocampal GMV. Amygdala GMV was related to CAR and social stress, with social overload being associated with reduced amygdala GMV in individuals not showing the typical CAR (reflecting a blunted physiological response to awakening), while the opposite pattern emerged in those with a typical CAR. CONCLUSIONS: The association between chronic social stress and HC and AMY volume is interacting with CAR-pattern and sex. The brain morphology in males and in individuals with an atypical CAR showed reductions in association with chronic social stress. Our findings point to a complex interaction between social stress, cortisol patterns, sex and brain architecture, which needs to be assessed in more detail in future research.