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Chronic stress-associated depressive disorders: the impact of HPA axis dysregulation and neuroinflammation on the hippocampus: a mini review


Citation

Lei, Ai Ai and Phang, Vanessa Wen Xian and Lee, Yu Zhao and Kow, Audrey Siew Foong and Tham, Chau Ling and Ho, Yu Cheng and Lee, Ming Tatt (2025) Chronic stress-associated depressive disorders: the impact of HPA axis dysregulation and neuroinflammation on the hippocampus: a mini review. International Journal of Molecular Sciences, 26 (7). art. no. 2940. pp. 1-13. ISSN 1661-6596; eISSN: 1422-0067

Abstract

Chronic stress significantly contributes to the development of depressive disorders, with the hypothalamic–pituitary–adrenal (HPA) axis playing a central role in mediating stress responses. This review examines the neurobiological alterations in the hippocampus linked to HPA axis dysregulation in chronic stress-associated depressive disorders. The prolonged activation of the HPA axis disrupts cortisol regulation, leading to the decline of both physical and mental health. The chronic stress-induced HPA axis dysfunction interacts with inflammatory pathways and generates oxidative stress, contributing to cellular damage and neuroinflammation that further aggravates depressive symptoms. These processes result in structural and functional alterations in the hippocampus, which is essential for emotional regulation and cognitive function. Comprehending the impact of chronic stress on the HPA axis and associated neurobiological pathways is essential for formulating effective interventions for depressive disorders. This review summarises the existing findings and underscores the necessity for future investigations into intervention strategies to improve physical and psychological wellbeing targeting at HPA axis dysregulation for the betterment of psychological wellbeing and human health.


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Additional Metadata

Item Type: Article
Subject: Catalysis
Subject: Molecular Biology
Subject: Spectroscopy
Divisions: Faculty of Medicine and Health Science
Institute of Bioscience
DOI Number: https://doi.org/10.3390/ijms26072940
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Keywords: Chronic stress; HPA axis; Human health; Major depressive disorder; Neuroinflammation; Oxidative stress
Sustainable Development Goals (SDGs): SDG 3: Good Health and Well-being, SDG 10: Reduced Inequalities, SDG 4: Quality Education
Depositing User: Ms. Nur Faseha Mohd Kadim
Date Deposited: 18 Jun 2026 04:22
Last Modified: 18 Jun 2026 04:23
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.3390/ijms26072940
URI: http://psasir.upm.edu.my/id/eprint/126117
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