Here is a newly published meta-analysis of cortisol associations...

Here is a newly published meta-analysis of cortisol associations with depression in younger people. It provides some new but not overwhelming additional evidence that cortisol elevation may be a causal factor, not just a biomarker, for the onset of early depression (MDD, major depressive disorder).

https://www.sciencedirect.com/science/article/pii/S0306453021004996

Psychoneuroendocrinology

Volume 136, February 2022, 105625

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

ARTICLE INFO
Keywords: Depression, Adolescence, Cortisol, HPA axis, Stress, Major depressive disorder
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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