Background and aims Depression has become a global disease burden, with the World Health Organisation reporting that more than 700,000 people with depression die by suicide every year. As of May 2023, approximately 280 million people worldwide suffer from depression. Despite the widespread reporting of preventive methods and interventions for depression, all countries around the globe have been unable to eliminate the burden of disease associated with depression. The prevailing conceptions of depression as a disease of inflammation have been increasingly substantiated by a plethora of research, which has in turn given rise to the development of a range of anti-inflammatory therapeutic interventions. This present scoping review aims to consolidate and organise all extant mechanisms describing inflammatory pathologies of depression, including systematic and scoping reviews, published and unpublished literature, with a view to facilitating the development of therapeutic potential based on inflammatory pathologies and the development of clinical guidelines. Method In conducting this scoping review, the framework developed by Arksey and O'Malley will be rigorously implemented. Five databases (i.e. PubMed, Embase, Scopus, Web of Science, and Cochrane Central) and grey literature will be searched. The results of the search will be imported into Zotero Literature Manager by one reviewer, who will subsequently remove duplicates. The other two reviewers will then screen the literature for titles, abstracts and full texts, and report any disagreements to the review inspectors, who will judge the results. The final documents will be extracted from the textual or numerical content of the documents according to our data extraction protocols, and summarised and consolidated in the form of images, tables or statistical graphs.The consolidated evidence will be used for discussion between clinical experts, pathologists and senior researchers. This collaborative discussion will yield a comprehensive understanding of the inflammatory pathomechanisms underlying depression, as well as preliminary inflammatory pathomechanism-targeted or holistic treatment protocols. These preliminary treatment protocols have the potential to be further developed into clinical depression treatment guidelines. Registration DOI: https://doi.org/10.17605/OSF.IO/SE49K Ethics and dissemination The literature employed for this scoping review was obtained from publicly available sources, having received ethical approval. The decision has been taken that no further animal or human testing will be conducted, and the methodology will be conducted in accordance with the principles of transparency and openness. Consequently, the necessity for additional ethics committee approval is eliminated. The findings of this scoping review will be subject to a rigorous peer-review process, and subsequently disseminated to the academic community through academic journals or at academic conferences. Discussion This scoping review will synthesise the evidence for all inflammatory pathologies of depression and develop initial targeted or holistic treatment options. Researchers focusing on depression at the animal level will have access to a comprehensive view of inflammatory pathology. This will standardise the design of complete animal studies and allow them to identify existing evidence of inflammatory mechanisms in a timely manner, thus avoiding wasted research resources. Furthermore, clinicians and psychotherapists will gain access to novel treatment options for depression that complement existing therapeutic interventions. The dissemination of the results of this research will facilitate the development of more authoritative and effective clinical guidelines for the treatment of depression, thereby contributing to global progress in eliminating the burden of disease associated with depression.

The authors have declared no competing interest.

https://doi.org/10.17605/OSF.IO/SE49K

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present work are contained in the manuscript.

https://osf.io/2phwv/