When the biological clock is disordered: circadian rhythm disruption as a core pathophysiological mechanism in anxiety and depression

Abstract

Anxiety and depressive disorders impose a heavy global burden. Although sleep disturbances have traditionally been regarded as secondary symptoms of these conditions, converging evidence now implicates circadian rhythm disruption as a core pathophysiological mechanism rather than a mere epiphenomenon. This review systematically explores the circadian system and constructs an integrated framework linking disruption to the synergistic dysregulation of multiple pathways and subsequent emotional/sleep abnormalities. We systematically examine five key mechanistic pathways: the SCN-limbic circuit, HPA axis, immune inflammation, neurotransmitter plasticity, and the gut-brain axis. Furthermore, we define actionable subtypes of disruption, summarize chronotherapies (e.g., light therapy, melatonin), and analyze current controversies regarding causality. Finally, we propose future directions, including multi-omics sampling and personalized intervention algorithms. By integrating evidence linking circadian disruption to anxiety/depression, this paper highlights its central mechanistic value, providing theoretical support for precision psychiatry and the integration of circadian medicine.