CLOCK and major depressive disorder: CRD has been identified associated with aging, immunocompromise, metabolic disorders, and mood disorders.[24, 25] The causal relationship between CRD and depression has been long investigated, with the main focus on the role of abnormal rhythmic gene expression in certain brain regions, which may contribute to the onset of depression by disturbing neuronal activity, regulating metabolism, and other pathways.[26, 27] Peripheral tissues and cells also express rhythmic genes, which are normally expressed in response to central clock, oscillating in cycles close to 24 h.