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Childhood adversity and allostatic overload of the hypothalamic–pituitary–adrenal axis: A vulnerability model for depressive disorders

Published online by Cambridge University Press:  21 October 2011

Paul O. Wilkinson  and
Ian M. Goodyer
Paul O. Wilkinson*
Affiliation:
University of Cambridge
Ian M. Goodyer
Affiliation:
University of Cambridge
*
Address correspondence and reprint requests to: Paul O. Wilkinson, University of Cambridge, Section of Developmental Psychiatry, Douglas House, 18b Trumpington Road, Cambridge CB2 8AH, UK; E-mail: pow12@cam.ac.uk.
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Abstract

Childhood adversity is associated with increased risk for onset of depressive episodes. This review will present evidence that allostatic overload of the hypothalamic–pituitary–adrenal axis (HPAA) partially mediates this association. The HPAA is the physiological system that regulates levels of the stress hormone cortisol. First, data from animals and humans has shown that early environmental adversity is associated with long-term dysregulation of the HPAA. This may occur due to permanent epigenetic modification of the glucocorticoid receptor. Second, data from humans has demonstrated that HPAA dysregulation is associated with increased risk of future depression onset in healthy individuals, and pharmacological correction of HPAA dysregulation reduces depressive symptoms. HPAA dysregulation may result in corticoid-mediated abnormalities in neurogenesis in early life and/or neurotoxicity on neural systems that subserve emotion and cognition.

Type
Articles
Information
Development and Psychopathology , Volume 23 , Issue 4: Allostatic Load: Part 2 , November 2011 , pp. 1017 - 1037
Copyright
Copyright © Cambridge University Press 2011

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