CHAPTER 11: Modulation of HPA Axis Function for Treatment of Mood Disorders

The current understanding of how molecular targets within the HPA axis can be used as modulation points for novel therapeutics to treat mood disorders and anxiety is summarized. Dysregulation of the HPA axis has long been implicated in playing a seminal role in the pathogenesis of mood disorders, and most specifically major depression. However, with few exceptions, the development of modulators of the HPA axis, such as CRF1 receptor, glucocorticoid (GC) or mineralcorticoid (MC) receptor antagonists to treat mood disorders either have been relatively unstudied or thus far lack efficacy. One notable exception reviewed here is mifepristone, a GC receptor antagonist that has shown promising results in a number of clinical trials. We also focus on non-classical targets within the HPA axis that also represent tractable therapeutic targets such as the CRF binding protein, arginine vasopressin, other neuropeptide receptors and novel targets identified by genetic studies. Additional clinical trials with a focus on disorders shown to dysregulate CRF and the HPA axis such as psychotic depression or major depression with early life trauma will likely yield important novel information about the patient subtypes likely to respond to such novel therapeutic approaches.