The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians
- PMID: 15014598
- PMCID: PMC181180
- DOI: 10.4088/pcc.v03n0401
The Hypothalamic-Pituitary-Adrenal Axis in Major Depressive Disorder: A Brief Primer for Primary Care Physicians
Abstract
BACKGROUND: One of the most enduring and replicated findings in biological psychiatry is activation of the hypothalamic-pituitary-adrenal (HPA) axis in a subset of patients with major depressive disorder. This review will discuss some of these findings and their pertinence to the assessment and treatment of depressed patients. METHOD: MEDLINE, PsychINFO, and Current Contents databases were searched for pertinent articles on the HPA axis in patients with depression. In addition, hand searches were conducted of references from these sources and abstracts from meetings and books on this topic. Articles that would provide an overview of major or interesting studies in the field were selected for inclusion. RESULTS: The data support that HPA axis activation is common in depressed patients. Frequently reported findings include elevated cortisol and corticotropin-releasing hormone (CRH), nonsuppression on the dexamethasone suppression test, a blunted adrenocorticotropic hormone (ACTH) response to CRH, and hippocampal volume reduction. Evidence of HPA axis activation appears to have prognostic value and is associated with increased risk of depression relapse and even suicide. CONCLUSION: Future research in this area will focus on a better understanding of the etiology and long-term consequences of HPA axis activation in depressed patients. In addition, medications that act on the HPA axis are currently in development and may be part of the psychiatrist's and primary care physician's pharmacopoeia in the near future.
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References
-
- Blazer DG, Kessler RC, McGonagle KA, et al. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am J Psychiatry. 1994;151:979–986. - PubMed
-
- Pandey GN. Altered serotonin function in suicide: evidence from platelet and neuroendocrine studies. Ann N Y Acad Sci. 1997;836:182–200. - PubMed
-
- Owens MJ, Nemeroff CB. The role of corticotropin-releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies. Ciba Found Symp. 1993;172:296–308. - PubMed
-
- Coplan JD, Andrews MW, Rosenblum LA, et al. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders. Proc Natl Acad Sci U S A. 1996;93:1619–1623. - PMC - PubMed
-
- de Kloet ER, Reul JMHM, Sutanto W. Corticosteroids and the brain. J Steroid Biochem Molec Biol. 1990;37:387–394. - PubMed
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