| Title: |
The HPA axis and kynurenine pathway: exploring the role of stress and neuroinflammation in treatment-resistant depression |
| Authors: |
Bose, Madhura M; Govindula, Anusha; Nampoothiri, Madhavan; Arora, Devinder; Mudgal, Jayesh |
| Publisher Information: |
Springer |
| Publication Year: |
2025 |
| Collection: |
Griffith University: Griffith Research Online |
| Subject Terms: |
Pharmacology and pharmaceutical sciences |
| Description: |
Treatment-resistant depression (TRD) continues to pose a major challenge in clinical practice, as a large proportion of patients fail to achieve remission despite multiple antidepressant drugs. Growing evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, together with epigenetic alterations, neuroinflammation, and kynurenine pathway metabolism, plays a central role in the pathophysiology of TRD. Particularly, prolonged stress-induced glucocorticoid receptor (GR) resistance, persistent hypercortisolaemia, and elevated pro-inflammatory cytokines contribute to neurotoxicity, hippocampal atrophy, and impaired neuroplasticity, aggravating depressive symptoms and reducing treatment response. Additionally, dysregulated tryptophan metabolism and the shift towards neurotoxic kynurenine metabolites further impair neuronal function and resulting in TRD. This review integrates recent findings on the complex interplay between HPA axis dysfunction, neuroimmune responses, and metabolic disturbances in TRD while highlighting novel therapeutic avenues such as ketamine, GR modulators, and anti-inflammatory agents. Further, disruption in the blood-brain barrier as one of the mechanisms of TRD was also reviewed. A deeper understanding of these mechanisms will enable the development of personalized treatment strategies to enhance clinical outcomes for TRD patients. ; Full Text |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Pharmacological Reports; Bose, MM; Govindula, A; Nampoothiri, M; Arora, D; Mudgal, J, The HPA axis and kynurenine pathway: exploring the role of stress and neuroinflammation in treatment-resistant depression, Pharmacological Reports, 2025; https://hdl.handle.net/10072/440247 |
| DOI: |
10.1007/s43440-025-00806-6 |
| Availability: |
https://hdl.handle.net/10072/440247; https://doi.org/10.1007/s43440-025-00806-6 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. ; open access |
| Accession Number: |
edsbas.E3BB8B33 |
| Database: |
BASE |