Abstract
Objective: To examine whether neuroinflammation can be understood as a unifying mechanism in major psychiatric disorders and summarized its molecular and clinical relevance. Major psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia, are increasingly linked with immune dysregulation and inflammatory signaling. Neuroinflammation may help explain shared biological mechanisms across these disorders, but the available evidence remains diverse and clinically heterogeneous.
Methods: This review followed PRISMA 2020 guidance. Electronic searches were conducted in PubMed, ScienceDirect, Cochrane Library, PubMed Central, and Embase for studies published between 2021 and 2026. Only English-language, human studies published between 2021 and 2026 were included. Studies had to address neuroinflammation or related neuroimmune mechanisms in depression, bipolar disorder, schizophrenia, or psychosis. Methodological quality was assessed using design-specific appraisal tools.
Results: All 2288 records were identified. 52 duplicates were removed; 2236 records were screened. Twenty-one full text reports were assessed for eligibility, and 15 studies were included in the final synthesis after exclusion of six full-text reports, including one study with high risk of bias. The included studies covered major depressive disorder, bipolar disorder, schizophrenia, first-episode psychosis, perinatal depression, perimenopausal depression, and cross-diagnostic postmortem datasets. Across these studies, neuroinflammatory involvement was reported through altered cytokines, complement proteins, matrix metalloproteinases, kynurenine-pathway metabolites, immune-cell changes, viral immune associations, and transcriptomic immune pathways. Some intervention studies also showed that symptom improvement was accompanied by favorable changes in inflammatory measures.
Conclusion: The available evidence supports an important but heterogeneous role of neuroinflammation across major psychiatric disorders. Current findings suggest shared immune-related mechanisms, but no single biomarker is sufficient as a universal diagnostic marker. Larger and better-designed studies are needed to clarify clinical relevance and therapeutic potential.
Article Type
Systematic Review
Supplementary file
First Page
326
Last Page
335
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Alammar, Muath A
(2026)
"Neuroinflammation as a Unifying Mechanism in Major Psychiatric Disorders: From Molecular Pathways to Clinical Implications: A Systematic Search and Review,"
Neurosciences: Vol. 31:
Iss.
4, Article 1.
DOI: https://doi.org/10.17712/1658-3183.2813