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Meta-Analysis
. 2022 Feb:136:105625.
doi: 10.1016/j.psyneuen.2021.105625. Epub 2021 Dec 8.

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

Zuzanna Zajkowska  1 , Nancy Gullett  1 , Annabel Walsh  1 , Valentina Zonca  2 , Gloria A Pedersen  3 , Laila Souza  4 , Christian Kieling  4 , Helen L Fisher  5 , Brandon A Kohrt  3 , Valeria Mondelli  6
Affiliations
Meta-Analysis

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

Zuzanna Zajkowska et al. Psychoneuroendocrinology. 2022 Feb.

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.

Keywords: Adolescence; Cortisol; Depression; HPA axis; Major depressive disorder; Stress.

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Conflict of interest statement

Dr Mondelli has received research funding from Johnson & Johnson as part of a research program on depression and inflammation, but the research described in this paper is unrelated to this funding. All other authors declare they have no conflicts of interest to report.

Figures

Fig. 1
Fig. 1
PRISMA Flow Diagram of Study Selection Process.
Fig. 2
Fig. 2
Forest plots of morning cortisol and adolescent depression in longitudinal studies (Fig. 2A) and in cross-sectional studies (2B).
Fig. 3
Fig. 3
Forest plots of afternoon cortisol (3A), evening cortisol (3B), and cortisol response to stress (3C) in adolescents with MDD compared with healthy adolescents.
See this image and copyright information in PMC

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