Structural brain correlates of symptom severity in stress-induced exhaustion.

Exhaustion due to chronic stress, a hallmark feature of burnout, represents a substantial and growing public health burden, yet its structural brain correlates remain poorly understood. We used voxel-based morphometry (VBM) to examine associations between regional gray matter volume and symptom severity in a cohort of 300 individuals on self-reported sick leave due to the Swedish medical condition stress-induced exhaustion disorder (ED), characterized by debilitating fatigue following prolonged stress exposure. Symptom severity was assessed using the Shirom-Melamed Burnout Questionnaire (SMBQ-18) and its subscales. Overall symptom severity (SMBQ-18 total score) and Physical Exhaustion (PE) were negatively associated with gray matter volume in the medial prefrontal cortex (mPFC), a region implicated in stress regulation and affective control, which remained significant when adjusting for depressive symptoms. An exploratory finding was that Listlessness was negatively associated with gray matter volume in the bilateral hippocampi and right middle temporal gyrus after adjustment for depressive symptoms. These results provide evidence from a large cohort for brain-symptom associations in chronic stress and highlight the value of dimensional approaches for capturing heterogeneity in stress-related conditions.