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Malaysia","award":["REIG-FPS-2022\/006"],"award-info":[{"award-number":["REIG-FPS-2022\/006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic stress significantly contributes to the development of depressive disorders, with the hypothalamic\u2013pituitary\u2013adrenal (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.<\/jats:p>","DOI":"10.3390\/ijms26072940","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:01:50Z","timestamp":1742817710000},"page":"2940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":218,"title":["Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus\u2014A Mini Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Ai Ai","family":"Lei","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Wen Xian","family":"Phang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Zhao","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4601-4286","authenticated-orcid":false,"given":"Audrey Siew Foong","family":"Kow","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-0372","authenticated-orcid":false,"given":"Chau Ling","family":"Tham","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Natural Medicine and Product Research Laboratory (NaturMeds), Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Cheng","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung City 82445, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3957-2439","authenticated-orcid":false,"given":"Ming Tatt","family":"Lee","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia"},{"name":"Office of Postgraduate Studies, UCSI University, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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