Linking Depression to Epigenetics: Role of the Circadian Clock.

The circadian clock governs multiple biological functions at the molecular level and plays an essential role in providing temporal diversity of behavior and physiology including neuronal activity. Studies spanning the past two decades have deciphered the molecular mechanisms of the circadian clock, which appears to operate as an essential interface in linking cellular metabolism to epigenetic control. Accumulating evidence illustrates that disruption of circadian rhythms through jet lag, shift work, and temporary irregular life-style could lead to depression-like symptoms. Remarkably, abnormal neuronal activity and depression-like behavior appear in animals lacking elements of the molecular clock. Recent studies demonstrate that neuronal and synaptic gene induction is under epigenetic control, and robust epigenetic remodeling is observed under depression and related psychiatric disorders. Thus, the intertwined links between the circadian clock and epigenetics may point to novel approaches for antidepressant treatments, epigenetic therapy, and chronotherapy. In this chapter we summarize how the circadian clock is involved in neuronal functions and depressive-like behavior and propose that potential strategies for antidepressant therapy by incorporating circadian genomic and epigenetic rewiring of neuronal signaling pathways.