Mechanisms of rumination in depression: neuroendocrine dysregulation, circadian disruption, and therapeutic interventions

Ruminative thinking, a persistent and passive focus on negative content, represents a key psychological mechanism underlying the onset and chronicity of depression. This review integrates advances in neurobiology, chronobiology and endocrinology to delineate the biological substrates through which rumination contributes to depressive pathology. Converging neuroimaging findings indicate that rumination does not arise from dysfunction in a single structure, but reflects coordinated alterations across distributed neural circuits supporting self-referential processing and executive control. Circadian rhythm disruption further impairs cognitive regulation and emotional stability, fostering sustained negative mentation. Dysregulation of the hypothalamic-pituitary-adrenal axis contributes an additional maintenance pathway through flattened cortisol rhythmicity and reduced stress-recovery capacity. Sleep-dependent emotional-memory processes enable repeatedly reactivated negative information to be reorganized and stabilized, whereas sleep disturbances undermine affective regulation and heighten susceptibility to intrusive rumination. Emerging evidence highlights the therapeutic potential of chronobiology-based interventions, targeted pharmacotherapies and neuromodulation approaches. Future work integrating dynamic biomarkers with individual circadian phenotypes will be crucial for developing precise, multidimensional strategies for rumination-associated depression.