Journal of Child Psychology and Psychiatry and Allied Disciplines

Psychoneuroendocrine stress response in female and male youth with major depressive disorder

Anka Bernhard 1, 2
Nikola Fann 1
Andreas G. Chiocchetti 1
Katharina Ackermann 1, 3
Anne Martinelli 1, 4
C. Freitag 1
1
 
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy University Hospital Frankfurt am Main, Goethe University Frankfurt am Main Germany
2
 
Department of Child and Adolescent Psychiatry and Psychotherapy Faculty of Medicine, Technische Universität Dresden, German Center for Child and Adolescent Health (DZKJ), Partner Site Leipzig/Dresden Dresden Germany
3
 
Faculty of Education, University Hamburg Hamburg Germany
4
 
Fresenius University of Applied Sciences Frankfurt am Main Frankfurt am Main Germany
Publication typeJournal Article
Publication date2025-03-23
scimago Q1
SJR3.133
CiteScore13.8
Impact factor6.5
ISSN00219630, 14697610
Abstract
Background

Exposure to psychosocial stress is one of the strongest risk factors for major depressive disorder (MDD) in youth, but underlying neurobiological mechanisms are poorly understood. Previous studies on the neuroendocrine stress response in youth with MDD are scarce, limited to cortisol, and rarely considered sex differences. Due to puberty‐associated neuroendocrine transitions increasing the risk for MDD onset in adolescence, this study aimed to investigate sex‐specific stress responses of stress and sex hormones as well as of neuropeptides.

Methods

In 103 pubertal youths with MDD and 72 healthy controls (HCs; 62% females, 12–18 years), psychological stress as well as salivary cortisol, testosterone, and oxytocin reactivity to a standardized psychosocial stress test (Trier Social Stress Test, TSST) were assessed. Effects of group and sex, and their interactions were analyzed using hierarchical linear models, while controlling for potentially confounding factors (such as age and pubertal status).

Results

Females and males with MDD showed a stronger psychological stress response than HCs. In contrast, both female and male youth with MDD showed blunted cortisol, testosterone, and oxytocin stress responses compared to HCs. In addition, baseline testosterone was elevated in MDD compared to HCs.

Conclusions

Results indicate a discrepant stress reactivity in youth with MDD, with increased psychological, but decreased neuroendocrine responses to psychosocial stress. Blunted neuroendocrine stress responses in youth with MDD were found across different neuroendocrine systems and in both females and males with MDD. These novel findings point to a fundamentally changed stress response in youth with MDD irrespective of sex, which may influence successful stress regulation in the affected adolescents.

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