CLOCK and major depressive disorder: This rhythm is driven by the periodicity of biological clock genes and clock-controlled genes.[49] In recent years, research focusing on the pathogenesis of depression has increasingly emphasized the hypothesis of circadian rhythm disorder.[50] Studies have revealed that dysregulation of biological clock genes contributes to the development of depression through the induction of neuroinflammation, abnormal activity of the HPA axis, and disturbances in neurotransmitter secretion.