ABSTRACT

One of the most consistent findings in biological psychiatry is derangement of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe mood disorders. The HPA axis consists of the hypothalamus, pituitary, and adrenal glands, various hormones and releasing factors, and regulatory neural inputs (1). It regulates the body’s acute response to stress, and its actions in this regard include mobilizing energy reserves through increased gluconeogenesis, lipolysis, and protein degradation (2). It also plays a role in long-term adaptive changes to physiological functions, for example, by modulating immune responses, facilitating learning, and activating the sympathetic nervous system (1). The purpose of this review is to examine the physiology of the HPA axis; outline the evidence for its implication in the pathogenesis of depression and bipolar disorder; summarize treatment options that may be efficacious in restoring normal HPA axis functioning, and thereby effective in treating mood disorders; and to suggest avenues for further research.