Brain-Derived Neurotrophic Factor Alterations in Completed Suicide: A Systematic Review

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated in the neurobiology of suicide, but findings remain inconsistent. We examined studies comparing BDNF-related measures in individuals who died by suicide and non-suicide controls. ISI Web of Science, Scopus, and Embase were searched from inception through to 31 July 2025 in accordance with PRISMA guidelines. Twenty studies met inclusion criteria. Most analysed postmortem brain tissue, while fewer investigated plasma, whole blood, or cerebrospinal fluid. Postmortem studies frequently reported reduced BDNF protein and/or mRNA expression in frontal and limbic regions. Several also described increased promoter methylation. In contrast, peripheral findings were heterogeneous, and studies of the Val66Met polymorphism did not demonstrate consistent associations with suicide. Overall, evidence supports region-specific alterations of central BDNF signalling in suicide, whereas peripheral and genetic findings remain inconclusive. Methodological variability across studies limits comparability. Larger investigations using standardised protocols are needed to clarify the role of BDNF in suicide mortality.