Role of stress in the development of depression

Abstract

In today’s stressful society, many people suffer from excessive stress, leading to subclinical and clinical depression. A variety of biological abnormalities associated with stress and depression have been reported, and among them, abnormalities in the hypothalamic‐pituitary‐adrenal (HPA) axis and immune/inflammatory system, both of which are centrally involved in the stress response, are thought to hold the key. However, findings on the HPA axis and inflammatory system in depression are somewhat inconsistent, and its etiology and pathophysiology have not been elucidated. To clarify the involvement of stress in depression, we have conducted studies targeting the HPA axis and inflammatory system, and also performed data‐driven transcriptome analyses using peripheral blood RNA. In doing this, we focused on adverse childhood experiences, personality characteristics, and circadian rhythms. The results suggested that psychological and physical stress vulnerabilities caused by severe stress that begins early in life, and by long‐term or repetitive stress, can represent one important route leading to the development of depression.