Structural brain correlates of stress-induced exhaustion: cross-sectional findings in an exhaustion disorder cohort

Exhaustion induced by chronic stress represents a substantial and increasing individual and societal burden. However, short- and long-term neurobiological effects of stress-induced exhaustion is poorly understood. We therefore initiated the PROMUS project, a high-powered longitudinal brain imaging study of stress-induced exhaustion in a cohort of 300 participants on sick leave for the medical condition exhaustion disorder (ED) at baseline. Here, we present the cross-sectional structural brain correlates of exhaustion symptom severity at baseline in this cohort. We used magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to assess associations between symptom severity and regional gray matter volumes in the cohort. Symptom severity was measured using the total score of the Shirom-Melamed Burnout Questionnaire (SMBQ), and the subscales Physical exhaustion, Listlessness, Cognitive weariness and Tension. All analyses were adjusted for age, intracranial volume, salary, education and sick leave duration. Total SMBQ scores and Physical exhaustion were negatively associated with gray matter volume in the ventromedial prefrontal cortex/medial orbitofrontal cortex, and right insular cortex. Listlessness was negatively associated with gray matter volume in the bilateral hippocampi, right insular cortex, left cingulate cortex and right middle temporal gyrus. These associations remained significant after adjusting for symptoms of depression, except for the insular cortex. No significant associations were observed for Cognitive weariness or Tension. These results support a link between stress-induced exhaustion and gray matter alterations of brain circuits involved in chronic stress, providing a basis for future neurobiologically informed research into the prevention or reversing of stress-related brain changes.