ESPE Yearbook of Paediatric Endocrinology

Psychoneuroendocrinology. 2022; 136: 105625. PMID: 34920399https://pubmed.ncbi.nlm.nih.gov/34920399/

Brief Summary: This is a systematic review and meta-analysis examined the relationship between cortisol and major depressive disorder in global youth (10–24 years old).

Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of major depressive disorder (MDD) in adulthood, however, limited information exists on the role of the HPA axis in depression in adolescence and young adulthood (1, 2). These authors conducted a systematic review and meta-analysis of research investigating the relationship between cortisol and major depressive disorder (MDD) in adolescence and young adulthood. An association between the dysregulation of the HPA axis and the pathophysiology of MDD has been suggested in the past, especially in adults.

The authors found that elevated morning, but not evening, cortisol concentration was prospectively associated with later MDD development in adolescence and young adulthood. Qualitative synthesis of the three studies examining nocturnal cortisol showed that higher nocturnal cortisol was both longitudinally and cross-sectionally associated with MDD in adolescence. However, morning cortisol concentrations did not significantly differ between healthy controls and subjects with MDD in cross-sectional studies. Afternoon cortisol and cortisol stress response also did not differ between adolescents with MDD and healthy controls.

These data suggest that elevated morning cortisol concentrations precede subsequent MDD onset in adolescence, regardless of being a first or recurrent episode of depression. This may suggest that elevated cortisol might be a predictor rather than a consequence of depression. Furthermore, cumulative exposure to stress which initially results in elevated cortisol, with time, leads to blunted cortisol response which overlaps with MDD onset.

References: 1. Whiteford H.A., Degenhardt L., Rehm J., Baxter A.J., Ferrari A.J., Erskine H.E., Charlson F.J., Norman R.E., Flaxman A.D., Johns N., Burstein R., Murray C.J., Vos T. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013; 382: 1575–1586. 2. Kennis M., Gerritsen L., van Dalen M., Williams A., Cuijpers P., Bockting C. Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis. Mol. Psychiatry. 2020; 25: 321–338.