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

Introduction: Depression 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 analysis: This 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 dissemination: This 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. Registration: This scoping review protocol is registered with the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/SE49K).