HPA axis function in mood disorders

Mood disorders rank among the leading causes of disability worldwide, and are characterized by biological, emotional, psychological and cognitive symptoms. The monoamine hypothesis of depression fails to provide a comprehensive theory to account for this complex symptomatology, or the therapeutic action of drugs currently available for the treatment of mood disorders. Alternative theories have focused on the function of the hypothalamic–pituitary–adrenal (HPA) axis, and particularly on the deleterious effects of hypercortisolemia on mood, cognition and neuronal architecture. This article reviews the evidence suggesting that HPA axis dysfunction and maladaptive responses to stress may have a central role in the pathophysiology of mood disorders. Recent novel therapeutic strategies that target the HPA axis are also discussed.