Brain-Derived Neurotrophic Factor Alterations in Completed Suicide. A systematic review: protocol

This project is a PRISMA-guided systematic review examining alterations in brain-derived neurotrophic factor (BDNF) in individuals who died by suicide compared with individuals who died from non-suicidal causes. The review focuses exclusively on completed suicide and includes studies assessing BDNF in postmortem brain tissue as well as peripheral biological samples, including blood (serum, plasma, or whole blood), cerebrospinal fluid, and urine. The primary objective is to synthesize available evidence regarding differences in BDNF expression and regulation between suicide decedents and non-suicide controls. Outcomes of interest include BDNF protein levels, mRNA expression, epigenetic modifications (e.g., DNA methylation), and genetic polymorphisms (e.g., Val66Met). Secondary objectives include evaluating region-specific findings within corticolimbic brain areas and examining methodological sources of heterogeneity across studies. A comprehensive search of ISI Web of Science, Scopus, and Embase was conducted from database inception through 31 July 2025 using the terms “BDNF” OR “brain-derived neurotrophic factor” AND “suicide.” Original research articles published in English and reporting quantitative comparisons between suicide and non-suicide groups were eligible. Studies focusing exclusively on suicidal ideation or attempts were excluded. Screening and data extraction were performed independently by two reviewers using a standardized extraction form. Given anticipated heterogeneity in tissue type, analytical methods, and outcome measures, a qualitative synthesis was performed rather than a meta-analysis. The review aims to clarify whether consistent patterns of central or peripheral BDNF alteration are observed in suicide mortality and to identify methodological limitations that may inform future research.