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Depression and Hypothalamic-Pituitary-Adrenal Activation: A Quantitative Summary of Four Decades of Research

Stetler, Cinnamon PhD; Miller, Gregory E. PhD

doi: 10.1097/PSY.0b013e31820ad12b
Original Articles

Objectives: To summarize quantitatively the literature comparing hypothalamic-pituitary-adrenal (HPA) axis function between depressed and nondepressed individuals and to describe the important sources of variability in this literature. These sources include methodological differences between studies, as well as demographic or clinical differences between depressed samples.

Methods: The current study used meta-analytic techniques to compare 671 effect sizes (cortisol, adrenocorticotropic hormone, or corticotropin-releasing hormone) across 361 studies, including 18,454 individuals.

Results: Although depressed individuals tended to display increased cortisol (d = 0.60; 95% confidence interval [CI], 0.54-0.66) and adrenocorticotropic hormone levels (d = 0.28; 95% CI, 0.16-0.41), they did not display elevations in corticotropin-releasing hormone (d = 0.02; 95% CI, −0.47-0.51). The magnitude of the cortisol effect was reduced by almost half (d = 0.33; 95% CI, 0.21-0.45) when analyses were limited to studies that met minimal methodological standards. Gender did not significantly modify any HPA outcome. Studies that included older hospitalized individuals reported significantly greater cortisol differences between depressed and nondepressed groups compared with studies with younger outpatient samples. Important cortisol differences also emerged for atypical, endogenous, melancholic, and psychotic forms of depression.

Conclusions: The current study suggests that the degree of HPA hyperactivity can vary considerably across patient groups. Results are consistent with HPA hyperactivity as a link between depression and increased risk for conditions, such as diabetes, dementia, coronary heart disease, and osteoporosis. Such a link is strongest among older inpatients who display melancholic or psychotic features of depression.

HPA = hypothalamic-pituitary-adrenal; ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; dex = dexamethasone; CI = confidence interval.

SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT.

From the Department of Psychology (C.S.), Furman University, Greenville, South Carolina; and the Department of Psychology (G.E.M.), University of British Columbia, Vancouver, British Columbia, Canada.

Address correspondence and reprint requests to Cinnamon Stetler, PhD, Department of Psychology, Furman University, 3300 Poinsett Hwy., Greenville, SC 29613. E-mail: cinnamon.stetler@furman.edu

Received for publication January 4, 2010; revision received November 1, 2010.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site www.psychosomaticmedicine.org.

Copyright © 2011 by American Psychosomatic Society
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