Impact of recent stressful life events in adulthood on brain structure in the context of diathesis for mental disorders

Recent stressful life events in adulthood, such as loss of job or divorce, are strong proximal predictors for mental disorders. According to the diathesis-stress model, stressful life events have an even bigger effect on mental health when an individual is vulnerable based on early developmental risk factors. The aim of this work was to investigate the diathesis-stress model on a brain-structural level. In three studies, we examined whether recent stressful life events in adulthood are associated with grey matter volume, measured with magnetic resonance imaging, and whether such associations are moderated by early environmental and genetic risk factors. As possible moderators we assessed adverse childhood experiences, childhood abuse, childhood maltreatment, paternal age, urbanicity, having a first-degree relative with major depressive disorder, and a polygenic score for neuroticism. We found a cross-sectional association between stressful life events experienced in the past six months and smaller grey matter volume in the medial orbitofrontal cortex. In subjects with a lifetime diagnosis of major depressive disorder, but not in healthy subjects, childhood abuse moderated this association: when depressive subjects experienced childhood abuse in childhood they had a stronger association between stressful life events and smaller grey matter volume. Furthermore, in a two year follow up study in healthy subjects, a longitudinal association between stressful in the previous two years and grey matter volume reductions in a dorsal cluster in the medial prefrontal cortex was found. This reduction was stronger when healthy subjects had adverse childhood experiences. Alterations of the medial prefrontal cortex including the medial orbitofrontal cortex are associated with a wide range of mental disorders. Stressful life events in adulthood affect the brain structure depending on the vulnerability of an individual. These changes might increase the risk of developing mental disorders. The present work is a first step of investigating the diathesis-stress model on a brain structural level.