Advance in Stress for Depressive Disorder

Stress is an adaptive response to environment aversive stimuli and a common life experience of one's daily life. Chronic or excessive stress especially that happened in early life is found to be deleterious to individual's physical and mental health, which is highly related to depressive disorders onset. Stressful life events are consistently considered to be the high-risk factors of environment for predisposing depressive disorders. In linking stressful life events with depressive disorder onset, dysregulated HPA axis activity is supposed to play an important role in mediating aversive impacts of life stress on brain structure and function. Increasing evidence have indicated the strong association of stress, especially the chronic stress and early life stress, with depressive disorders development, while the association of stress with depression is moderated by genetic risk factors, including polymorphism of SERT, BDNF, GR, FKBP5, MR, and CRHR1. Meanwhile, stressful life experience particularly early life stress will exert epigenetic modification in these risk genes via DNA methylation and miRNA regulation to generate long-lasting effects on these genes expression, which in turn cause brain structural and functional alteration, and finally increase the vulnerability to depressive disorders. Therefore, the interaction of environment with gene, in which stressful life exposure interplay with genetic risk factors and epigenetic modification, is essential in predicting depressive disorders development. As the mediator of environmental risk factors, stress will function together with genetic and epigenetic mechanism to influence brain structure and function, physiology and psychology, and finally the vulnerability to depressive disorders.