Publication Name	World Journal of Psychiatry
Manuscript ID	125825
DOI	10.5498/wjp.125825
Country	China

Category	Psychiatry
Manuscript Type	Review
Article Title	Bidirectional cortisol dysregulation in depressive disorders: Pathophysiological mechanisms and therapeutic implications
Manuscript Source	Invited Manuscript
All Author List	Zi-Xuan Chen, Rula Sa, Zhi Wen, Rui-Ting Ma and Li-Jun Tong
Funding Agency and Grant Number	Funding Agency Grant Number The Science and Technology Project of the Inner Mongolia Public Hospitals Research Joint Fund No. 2025GLLH0280 the 2025 Inner Mongolia Health Science and Technology Program Project No. 2025WSJK066 the Project of the Physicians Association of Inner Mongolia Autonomous Region No. YSXH2024KYF015 the Top Talent Program for the YingCai XingMeng
Corresponding Author	Li-Jun Tong, Chief Physician, Dean, Mental Health College, Inner Mongolia Medical University, 400 meters northeast of the intersection of Yili Street and Chilechuan Road, Tumd Zuoqi, Hohhot 010110, Inner Mongolia Autonomous Region, China. tonglijun2022@126.com
Key Words	Major depressive disorder; Cortisol dysregulation; Hypothalamic-pituitary-adrenal axis; Glucocorticoid receptor; Neuroinflammation
Core Tip	Cortisol dysregulation in depressive disorders is heterogeneous, not uniformly hypercortisolemic. Subsets of melancholic and psychotic depression show increased exposure and impaired feedback. Lower output, blunted dynamic responses, enhanced dexamethasone suppression, and peripheral-cell glucocorticoid sensitivity vary by population and measure and need not co-occur. Findings in trauma-related samples or those with comorbid posttraumatic stress disorder should not be generalized to major depressive disorder. These patterns neither validate clinical subtypes nor justify cortisol-guided treatment. Inflammation and kynurenine metabolism may converge, but evidence remains incomplete. Future studies should integrate cortisol output, circadian rhythm, feedback, receptor function, and immune status.
Citation	Chen ZX, Sa R, Wen Z, Ma RT, Tong LJ. Bidirectional cortisol dysregulation in depressive disorders: Pathophysiological mechanisms and therapeutic implications. World J Psychiatry 2026; In press DOI: https://doi.org/10.5498/wjp.125825
PDF	125825-in-press.pdf

Received	2026-07-20 09:15
Peer-Review Started	2026-07-20 09:16
First Decision by Editorial Office Director
Return for Revision	2026-09-08 08:39
Revised	2026-09-21 10:51
Publication Fee Transferred
Second Decision by Editor	2026-11-02 02:18
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-11-02 03:23
Articles in Press	2026-11-02 03:23
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2220-3206 (online)
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