Overwork and structural alterations in serotonin–melatonin-related brain systems in healthcare workers

Background Long working hours are linked to sleep disturbance, fatigue and an increased risk of cardiometabolic and mental disorders; however, the neurobiological mechanisms underlying impaired recovery remain unclear. Overwork-related sleep complaints appear to arise primarily from sustained hyperarousal rather than circadian phase disruption. Methods We conducted a multimodal MRI study of 129 healthcare workers from a tertiary hospital cohort, including structural MRI, diffusion tensor imaging and resting-state functional MRI. Overwork was defined as working >52 hours per week. Structural analyses focused on serotonergic brainstem nuclei and the pineal gland, microstructural analyses examined thalamus–medial prefrontal cortex white matter pathways, and resting-state functional connectivity analyses examined networks involving default mode hubs, the brainstem and the pineal gland. Results Overworked workers showed larger periaqueductal gray and dorsal raphe nucleus volumes, smaller total and parenchymal pineal gland volumes and higher mean and radial diffusivity in the right thalamus–medial prefrontal cortex tract than non-overworked workers. No resting-state functional connectivity differences remained statistically significant after false discovery rate correction. Associations between weekly working hours and the structural and microstructural measures were observed in complementary continuous analyses. Conclusions Overwork was associated with structural and microstructural alterations in brain regions and pathways related to arousal and recovery in healthcare workers. These cross-sectional findings are hypothesis-generating and require confirmation in larger longitudinal studies. The observed structural and microstructural findings may be relevant to neural systems involved in arousal and recovery; however, direct measures of sleep, melatonin signalling and longitudinal exposure are needed to clarify their clinical and biological significance.