Stress and depression: clinical, neurobiological and genetical perspectives - S.J. Claes -

Major depressive disorder (mdd) can be elicited by various kinds of stress, such as negative life events, chronic stress and experiences of abuse early in life. These stressors interact with personality traits and with a genetic predisposition to depression, thereby bringing about mdd. Therefore, the neurobiology of depression cannot be separated from the neurobiology of stress system. A substantial number of publications have in fact demonstrated that mdd patients show abnormalities of the hypothalamic-pituitary-adrenal (hpa) axis, which is a key element of the stress response. Such disturbances are exacerbated by chronic stress, early experiences of abuse and even prenatal exposure to stress. On the other hand, genetic variations can play a role in the hpa axis dysfunction and in vulnerability to depression. Evidence is emerging that certain genes are directly involved in the functioning of the hpa axis. Other genetic factors, not directly related to the hpa axis, are probably relevant as well, the best known example being the serotonin transporter gene.