Circadian regulation of depression: A role for serotonin

Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models, Finally, we provide evidence that 5-HT is a critical factor linking dysregulation of the circadian system and mood. Determining how these two systems interact may provide novel therapeutic targets for depression.