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This version published online on February 14, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2397
A more recent version of this article appeared on May 1, 2006
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Submitted on November 3, 2005
Accepted on February 2, 2006

Disordered Adrenocorticotropin Secretion in Women with Major Depression

Elizabeth A Young* and Johannes D. Veldhuis

Department of Psychiatry and Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor and Endocrine Research Unit, Department of Internal Medicine, Mayo Medical and Graduate Schools, Rochester Minnesota

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

Context: Major depression is accompanied by activation of the hypothalamic pituitary axis and evidence of abnormalities in circadian and ultradian hormone rhythms. In addition, diminished negative feedback of cortisol on ACTH (ACTH) has been found.

Objective: To compare ACTH and cortisol hormonal patterns in women with major depression to normal control women.

Design: Case control study.

Setting: General-Clinical Research Center

Patients and Other Participants: Healthy, drug free, premenopausal women with major depression and age and menstrual cycle day matched healthy control women.

Main Outcome Measure: ACTH and cortisol data measured every 10 min for 24H analyzed with approximate entropy and cross-approximate entropy to determine orderliness of hormone secretion and relationship between ACTH and cortisol in terms of feed forward and feedback synchrony.

Results: Depressed women manifested increased approximate entropy, indicating more disorderly secretion, of ACTH and elevated forward cross-approximate entropy of ACTH on cortisol, denoting unopposed ACTH drive.

Conclusions: These data support other evidence of hormonal rhythm abnormalities in depression and are compatible with accentuated feedforward drive by ACTH.


Key words: ultradian hormone rhythms • circadian rhythms • hypothalamic-pituitary-adrenal axis







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