The HPA Axis in the Pathogenesis and Treatment of Depressive Disorders: Integrating Clinical and Molecular Findings

Studies over the last forty years have demonstrated that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent biological findings in major depression, but much of the mechanisms underlying this abnormality are still unclear. This review will elaborate on both the clinical and molecular role of the neuroendocrine stress system in depressive disorder and present some of the most recent findings that have shed light on the complex interface between environmental stressors, molecular mechanisms and clinical presentation. Further, psychopharmacological development have demonstrated both effects of conventional treatments on HPA functioning as well as of novel treatments targeting HPA functioning on clinical outcome.