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This version published online on February 22, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1056
A more recent version of this article appeared on May 1, 2005
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Submitted on June 7, 2004
Accepted on February 10, 2005

On the Interactions of the HPA Axis and Sleep: Normal HPA Axis and Rhythm, Exemplary Sleep Disorders

Theresa M. Buckley MD, MS* and Alan F. Schatzberg MD

Stanford Sleep Disorders Clinic and Research Center and Department of Psychiatry, 401 Quarry Rd., Suite 3301, Stanford, CA 94305; Department of Psychiatry, Stanford University, 401 Quarry Road, Stanford, CA 94305

* To whom correspondence should be addressed. E-mail: tbuckley{at}stanford.edu.

The hypothalamic-pituitary-adrenal (HPA) axis plays important roles in maintaining alertness and modulating sleep. Dysfunction of this axis at any level (CRH receptor, glucocorticoid receptor, mineralocorticoid receptor) can disrupt sleep. Herein, we review normal sleep, normal HPA axis physiology and rhythm, the effects of the HPA axis on sleep, as well as the effects of sleep on the HPA axis. We also discuss the potential role of CRH in circadian-dependent alerting, aside from its role in the stress response. Clinically relevant sleep disorders with likely HPA axis dysfunction - insomnia and obstructive sleep apnea - are discussed. In insomnia, we discuss how HPA axis hyperactivity may be partially causal to the clinical syndrome. In obstructive sleep apnea, we discuss how HPA axis hyperactivity may be a consequence of the disorder and result in secondary pathology. Mechanisms by which cortisol can effect slow wave sleep are discussed as is the role the HPA axis can play in secondary effects of primary sleep disorders.
Key words: HPA Axis • Sleep • Circadian • Insomnia • OSA HPA Axis and Rhythm and Sleep




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