The neuroimmunology of stress and depression.

This article reviews evidence that shows a bidirectional relationship between the brain and the immune system. As a result of this relationship, mental factors such as stress and depression have been shown to affect immune system functioning, with both immunosuppression and immune activation being reported. Stress and depression also have been associated with worse outcomes in immune-related disorders including cancer and infectious diseases suggesting that stress/depression effects on the immune system are clinically relevant to disease expression. Conversely, several lines of evidence suggest that immune system activation such as during infectious diseases, cancer, and autoimmune disorders is associated with the development of behavioral symptoms similar to those seen in the context of chronic stress or major depression. These findings implicate a role for the immune system in the cause of behavioral disorders in a wide range of medical illnesses. Finally, a paradigm is proposed in which abnormal functioning of either the hypothalamic-pituitary-adrenal (HPA) axis or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems contributing to the development of neuropsychiatric and immunologic disorders.