Abstract
BACKGROUND: Major depressive disorder (MDD) is a complex and heterogeneous condition. Current diagnosis relies on symptom-based assessments, leading to varied treatment responses. Data-driven approaches have attempted to identify MDD subtypes, but their clinical applicability remains limited. Traditional Chinese Medicine (TCM) provides a theory-driven classification system that categorizes MDD into syndrome subtypes of deficiency pattern and excess pattern, offering insights into the biological mechanisms and personalized treatment strategies. OBJECTIVE: This systematic review and meta-analysis aims to identify potential neurobiological distinctions of TCM-based deficiency and excess patterns in MDD by examining differences in the brain activity by using various functional magnetic resonance imaging (fMRI) modalities, including resting-state and task-based fMRI, diffusion tensor imaging, and magnetic resonance spectroscopy. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P), we will conduct a comprehensive search of 7 electronic databases (PubMed, Embase, Web of Science, Chinese Biological Medical Literature database, China National Knowledge Infrastructure, Chinese Wanfang database, and Chongqing VIP database) for studies published up to December 2024. Eligible studies will be screened by 2 independent reviewers based on predefined inclusion criteria, followed by data extraction and quality assessment. For the meta-analysis, resting-state fMRI studies will be analyzed in Montreal Neurological Institute space using Seed-based d Mapping-Permutation of Subject Images software (version 6.21), enabling a focused evaluation of brain activity differences in deficiency and excess MDD patterns. RESULTS: The search and screening for the systematic literature review were completed in December 2024. This study relies on published, publicly accessible data. We found approximately 30 eligible studies in our preliminary search, suggesting that a quantitative meta-analysis is feasible. Data extraction, quality appraisal, and subsequent data synthesis will begin in September 2025. The review should be completed by December 2025, and the study results will be published in 2026. CONCLUSIONS: The results of this study may help to explain the neural mechanisms of depression's neurobiological subtypes from the perspective of TCM. TRIAL REGISTRATION: PROSPERO CRD42023475178; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023475178. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/68996.