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Hypothalamic-Pituitary-Adrenal Axis Dysfunction by Early Life Stress

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number136037
Pages (from-to)136037
JournalNeuroscience Letters
Early online date8 Jun 2021
E-pub ahead of print8 Jun 2021
Published10 Aug 2021

Bibliographical note

Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MF Juruena Honorary Consultant at South London and Maudsley NHS Foundation Trust (SLaM-NHS UK). Professor AH Young is the Director of the Centre for Affective Disorders and is supported by the National Institute for Health Research (NIHR); Biomedical Research Centre (BRC) at SLaM-NHS UK IoPPN, King's College London. Professor AJ Cleare is supported by NIHR, BRC and SLaM-NHS UK. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. MF Juruena has within the last year received honoraria for speaking from Janssen, Lundbeck, EMS, Abbott and Daiichi-Sankyo. AJ Cleare has within the last 3 years received honoraria for lectures or consulting from Lundbeck, Livanova, Janssen & Allergan, and a research grant from Protexin Probiotics International Ltd. AH Young received honoraria for lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders. Investigator-initiated studies from AZ, Eli Lilly and Lundbeck. M. Bourne has no conflicts of interest to declare. Only the authors were involved in the study design and preparation of this report. Funding Information: This work was supported by Academy of Medical Sciences/Royal Society,UK (MF Juruena) and National Institute for Health Research (NIHR); Biomedical Research Centre (BRC) at SLaM-NHS UK IoPPN, King's College London. Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


King's Authors


Evidence indicates that early life stress (ELS) may act as a risk factor for the development and maintenance of adulthood severe mental health disorders due to persistent dysregulation within the hypothalamic-pituitary-adrenal (HPA) axis. It is now broadly accepted that psychological stress may change the internal homeostatic state of an individual. The dysregulation seems to be a byproduct of changes noted in the HPA axis hormone's ability to bind to the glucocorticoid and mineralocorticoid receptors, crucial in maintaining homeostasis. Whenever there is an acute interruption of this balance, illness may result. The social and physical environments have an enormous impact on our physiology and behavior, and they influence the process of adaptation or 'allostasis'. The HPA axis response to stress can be thought of as a mirror of the organism's response to stress: acute responses are generally adaptive, but excessive or prolonged responses can lead to deleterious effects. Evidence indicates that early-life stress can induce persistent changes in the ability of the HPA axis to respond to stress in adulthood This review aims to examine and summarise the existing literature exploring the relationship between ELS with regards specifically to HPA axis functioning. The maintenance of the internal homeostatic state of an individual is proposed to be based on the ability of circulating glucocorticoids to exert negative feedback on the secretion of HPA hormones through binding to mineralocorticoid (MR) and glucocorticoid (GR) receptors limiting the vulnerability to diseases related to psychological stress in genetically predisposed individuals.

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