CLOCK and major depressive disorder: Previous studies have shown that the potential neurobiological mechanisms of depression and insomnia symptoms may have included: (1) abnormalities in monoamine neurotransmitters, especially changes in 5-HT concentration, which were closely related to sleep awakening and depression, such as shortened REM latency in patients with depression; (2) Overexpression of biological clock genes and stress response genes; (3) Dysfunction of the hypothalamic pituitary adrenal axis (HPA) and abnormal release of cortisol (74).