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Cortisol and development of depression in adolescence and young adulthood – a systematic review and meta-analysis

Research output: Contribution to journalArticlepeer-review

Zuzanna Zajkowska, Nancy Gullett, Annabel Walsh, Valentina Zonca, Gloria A. Pedersen, Laila Souza, Christian Kieling, Helen Fisher, Brandon A Kohrt, Valeria Mondelli

Original languageEnglish
Article number105625
JournalPsychoneuroendocrinology
Volume136
Early online date8 Dec 2021
DOIs
Accepted/In press6 Dec 2021
E-pub ahead of print8 Dec 2021
PublishedFeb 2022

Bibliographical note

Funding Information: We are extremely grateful to all members of the IDEA team for their dedication, hard work, and insights. The IDEA project is funded by an MQ Brighter Futures grant [MQBF/1 IDEA]. Additional support was provided by the UK Medical Research Council [MC_PC_MR/R019460/1] and the Academy of Medical Sciences [GCRFNG\100281] under the Global Challenges Research Fund. VM is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. CK is a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) researcher and an Academy of Medical Sciences Newton Advanced Fellow. HLF is part supported by the Economic and Social Research Council (ESRC) Centre for Society and Mental Health at King's College London [ES/S012567/1]. CK and BAK are supported by the U.S. National Institute of Mental Health [R21MH124072]. The views expressed are those of the authors and not necessarily those of the funders, the NHS, the NIHR, the Department of Health and Social Care, the ESRC, or King's College London. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: The IDEA project is funded by an MQ Brighter Futures grant [ MQBF/1 IDEA ]. Additional support was provided by the UK Medical Research Council [ MC_PC_MR/R019460/1 ] and the Academy of Medical Sciences [ GCRFNG\100281 ] under the Global Challenges Research Fund . VM is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. CK is a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) researcher and an Academy of Medical Sciences Newton Advanced Fellow. HLF is part supported by the Economic and Social Research Council (ESRC) Centre for Society and Mental Health at King’s College London [ ES/S012567/1 ]. CK and BAK are supported by the U.S. National Institute of Mental Health [ R21MH124072 ]. The views expressed are those of the authors and not necessarily those of the funders, the NHS, the NIHR, the Department of Health and Social Care, the ESRC, or King’s College London. Publisher Copyright: © 2021

King's Authors

Abstract

Introduction: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood. Less work has focused on the role of the HPA axis in depression in adolescence and young adulthood globally. The aim of this study was to conduct a systematic review and meta-analysis of worldwide research investigating the relationship between cortisol, a measure of HPA axis activity, and MDD in adolescence and young adulthood. Method: We searched MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, Web of Science, Lilacs, African Journals Online, and Global Health for studies which examined the relationship between cortisol and MDD in global youth (10–24 years old). Results: Twenty-six studies were included in the systematic review and 14 were eligible for the meta-analysis, but only one study included young adults in their sample. Results from the meta-analysis demonstrated that elevated morning, but not evening, cortisol levels was prospectively associated with later MDD development in adolescence and young adulthood. However, morning cortisol levels did not significantly differ between healthy controls and individuals with MDD in cross-sectional studies. Afternoon cortisol and cortisol stress response also did not differ between adolescents with MDD and healthy controls. Qualitative synthesis of the three studies examining nocturnal cortisol showed higher nocturnal cortisol was both longitudinally and cross-sectionally associated with MDD in adolescence. Conclusion: Our findings suggest elevated morning cortisol precedes depression in adolescence. Despite this, we did not find any differences in other cortisol measures in association with MDD in cross-sectional studies. Taken together, these findings suggest that elevated morning and nocturnal cortisol are risk factors for depression in adolescence rather than a biomarker of existing MDD. This supports a role for the hyperactivity of the HPA axis in the development of MDD in adolescence. Most of the studies were from high-income-countries (HICs) and thus further work would need to be conducted in low- and middle-income countries (LMICs) to understand if our findings are generalisable also to these populations.

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