ReviewPharmacological reports : PR2026
The HPA axis and kynurenine pathway: exploring the role of stress and neuroinflammation in treatment-resistant depression.
Review in Pharmacological reports : PR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota-Gut-Brain Axis's Neural, Immune, and Metabolic Routes.Biomolecules · 2026Review
- Molecular and Cellular Mechanisms Linking Mood Disorders, HPA Axis Dysregulation, and Neurocognitive Inflammation to Perioperative Neurocognitive Disorders.Biomolecules · 2026Review
- Neurobiology of Anxiety and Depression in CP/CPPS: A Narrative Review of Underlying Mechanisms.Neurology international · 2026Review
- The synaptic triad in depression: how stress-related pathways converge on BDNF, NMDA receptor, and MMP-9.Pharmacological reports : PR · 2026Review
- The Role of Exosomes in the Regulation of Molecular Mechanisms Underlying Treatment Resistance-Linking Cellular Crosstalk to Clinical Implications in Depression.International journal of molecular sciences · 2026Review
- Serum inflammatory cytokines in the progression of depression.Frontiers in immunology · 2026Review
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Ceramides and neuroinflammation as immunometabolic drivers and biomarkers of major depressive disorder, treatment-resistant depression, and suicidal vulnerability.Frontiers in pharmacology · 2026Review
- Neuroprotective effects of low-dose ionizing radiation in diabetic rats exposed to chronic unpredictable stress.Journal of advanced veterinary and animal research · 2026Article
- Neuroinflammation and treatment resistance in major depressive disorder.Frontiers in pharmacology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.