AccScience Publishing / JCBP / Online First / DOI: 10.36922/JCBP025490093
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REVIEW ARTICLE

Effect of inflammation and anti-inflammatory interventions on mental health and cognitive function: A systematic review

Sreeja Roy1,2 ,  Bianca M. Oană3 ,  Grace Adams4 ,  Sofia Arvanitis5 ,  Alena Ho3 ,  Anirudh Gupta6 ,  Megan Lopez7,8 ,  Lexi Clark7,9 ,  Amir Kanbar3 ,  Areej Abdul Aziz Aziz3 ,  Kyle Valentino2,10,11*
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1 Department of Biological Sciences, Indian Institute of Science Education and Research, Tirupati, Andhra Pradesh, India
2 Epigenetics & Neurobiology Unit, EMBL Rome, European Molecular Biology Laboratory, Rome, Italy
3 Department of Biological Sciences, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada
4 Department of Biological Sciences, Faculty of Arts and Sciences, Paradise Valley Community College, Phoenix, Arizona, United States
5 Department of Biological Sciences, Faculty of Arts and Sciences, Arizona State University, Phoenix, Arizona, United States
6 Department of Chemical Sciences, National Institute of Science Education and Research, Bhubaneswar, Odisha, India
7 Department of Human Biology, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada
8 Department of Molecular Genetics and Microbiology, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada
9 Department of Physiology, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada
10 Department of Pharmacology and Toxicology, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada
11 Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada
JCBP, 025490093 https://doi.org/10.36922/JCBP025490093
Received: 3 December 2025 | Revised: 2 April 2026 | Accepted: 14 April 2026 | Published online: 16 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Inflammation is increasingly recognized as a mechanistic pathway influencing both mental health and cognition. Elevated C-reactive protein (CRP) and interleukin-6 (IL-6) have been implicated in depressive symptom severity, treatment resistance, and impaired cognitive function. Anti-inflammatory agents, including biologics, nonsteroidal anti-inflammatory drugs (NSAIDs), statins, and adjunctive antibiotics, have been investigated in randomized controlled trials (RCTs) as potential treatments for mood and cognitive disorders. This systematic review synthesizes evidence on the association between inflammation and mental health outcomes and evaluates the efficacy of anti-inflammatory interventions. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, MEDLINE, Cochrane Library, PsycInfo, Embase, Scopus, and Web of Science were searched through July 30, 2024. Eligible studies were RCTs of Food and Drug Administration-approved anti-inflammatory agents reporting validated mental health or cognitive outcomes. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Twenty-one RCTs met the inclusion criteria (sample sizes: 28–38,807; mean ages: 18–84 years). Elevated CRP and IL-6 predicted poor antidepressant response and accelerated cognitive decline, especially in executive and learning/memory domains (hazard ratio: 1.6, 95% confidence interval: 1.2–2.1, p = 0.004). Biologics reduced depressive symptoms in high-inflammation subgroups (CRP > 5 mg/L; mean difference on the Hamilton Depression Rating Scale: −4.2; 95% confidence interval: −6.7 to −1.8; p < 0.001). Adjunctive celecoxib improved mania scores in bipolar disorder (Young Mania Rating Scale: Δ −4.8, p = 0.02) but had inconsistent effects in depression. Statins and aspirin showed no preventive benefit for depression, with some evidence of slightly worsened symptom trajectories in older adults. Minocycline improved depressive symptoms in patients with inflammatory profiles (Montgomery– Åsberg Depression Rating Scale difference: −3.7, p = 0.01). Cognitive outcomes were rarely primary endpoints, and anti-inflammatory interventions generally showed no significant benefit on executive function, attention, or social cognition. These findings support prioritizing biomarker-stratified trials to develop precision anti-inflammatory treatments in psychiatry. 

Keywords
Inflammation
Depression
Cognition
Anti-inflammatory agents
Biologics
Nonsteroidal anti-inflammatory drugs
Minocycline
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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