The Role of Inflammation in Depression: A Scoping Review Protocol in Mechanisms, Evidence, and Therapeutic Potential

IntroductionDepression is a leading global cause of disability and premature mortality, yet a substantial proportion of patients do not respond adequately to standard treatments. An increasing body of evidence suggests that inflammatory processes contribute to the onset, persistence, and recurrence of depression; however, this evidence remains fragmented across basic, translational, and clinical research domains. Methods and analysisThis scoping review aims to systematically map the existing evidence on the role of inflammation in depression and to characterise how inflammatory markers and pathways have been investigated in relation to prevention and treatment strategies. The review will be conducted in accordance with established methodological guidance for scoping reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Multiple bibliographic databases, trial registries, grey literature sources, and preprint servers will be searched without language restrictions. Two reviewers will independently screen records, select eligible studies, and chart data using a piloted data extraction form. Findings will be synthesised using descriptive statistics and narrative methods to summarise study characteristics, inflammatory mechanisms, biomarkers, interventions, and clinical outcomes. An integrative framework will be developed to link inflammatory mechanisms with therapeutic and preventive approaches. Ethics and disseminationThis review will use only publicly available data, and no new data will be collected; therefore, formal ethical approval is not required. The findings will be disseminated through peer-reviewed publication and other academic dissemination channels to support knowledge translation in depression research. RegistrationThis scoping review protocol is registered with the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/SE49K). Strengths and limitations of this studyO_ST_ABSStrengthsC_ST_ABS{blacksquare} This scoping review provides a comprehensive synthesis of mechanistic evidence examining the role of inflammation in depression, integrating findings across clinical, preclinical, and translational research. {blacksquare}The inclusion of grey literature and preprints enhances the breadth of evidence captured and reduces the risk of publication bias. {blacksquare}Transparency and reproducibility are strengthened through prospective protocol registration, adherence to established scoping review guidelines, and peer review of the research process. Limitations{blacksquare} As a scoping review, this study does not undertake formal critical appraisal of individual studies or quantitative synthesis of effect sizes, which limits causal inference. {blacksquare}The heterogeneity of study designs, populations, and inflammatory measures may constrain direct comparison across studies. {blacksquare}Reliance on published and publicly available sources may result in incomplete capture of unpublished or ongoing research.