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

Zuzanna Zajkowska, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Nancy Gullett, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Annabel Walsh, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Valentina Zonca, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK; Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Gloria A. Pedersen, Division of Global Mental Health, Department of Psychiatry, School of Medicine and Health Sciences, The George Washington University, 2120L St NW, Ste 600, Washington, DC 20037, USA.
Laila Souza, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 - 400N, Porto Alegre, RS 90035-903, Brazil.
Christian Kieling, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350 - 400N, Porto Alegre, RS 90035-903, Brazil.
Helen L. Fisher, King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK; ESRC Centre for Society and Mental Health, King's College London, London, UK.
Brandon A. Kohrt, Division of Global Mental Health, Department of Psychiatry, School of Medicine and Health Sciences, The George Washington University, 2120L St NW, Ste 600, Washington, DC 20037, USA.
Valeria Mondelli, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK; National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, King's College London, London, UK. Electronic address: valeria.mondelli@kcl.ac.uk.

Document Type

Journal Article

Publication Date

2-1-2022

Journal

Psychoneuroendocrinology

Volume

136

DOI

10.1016/j.psyneuen.2021.105625

Keywords

Adolescence; Cortisol; Depression; HPA axis; Major depressive disorder; Stress

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.

Department

Psychiatry and Behavioral Sciences

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