The role of brain-derived neurotrophic factor in cardiometabolic disease and mental health within the spinal cord injury population: a systematic review

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a protein crucial to the survival, growth, and differentiation of neurons in the brain and spinal cord. BDNF is monitored across many populations as an indicator of one's cardiometabolic disease (CMD) and mental health (MH) risk. Adults living with a traumatic spinal cord injury (tSCI) are at a higher risk of developing CMD and MH issues, with symptoms often going unrecognized. Establishing serum BDNF as a screening tool within the tSCI population has the potential to improve CMD and MH symptom recognition. OBJECTIVES: This systematic review aims to: (1) explore the tSCI literature to determine whether an association exists between serum BDNF, MH, and CMD risk(s); and; (2) identify best-practice BDNF sampling techniques within the tSCI population. METHODS: A comprehensive search strategy was developed in collaboration with a University Health Network Librarian. Six databases (MEDLINE, Embase, CENTRAL, APA PsycInfo, CINAHL Ultimate, and Web of Science Core Collection) were searched to identify English-language studies published from inception to July 2025. Studies which reported serum BDNF in the tSCI population in addition to either MH or CMD and have three or more human participants with acute or chronic tSCI were included. Duplicate abstracts were removed and the remaining titles and abstracts reviewed and selected for full-text screening. Study quality was assessed for potential risk of bias using Downs and Black Checklist (Clinical Trials), Newcastle-Ottawa Score (Case-Control Study), or Joanna Briggs Institute Checklist (Cross-sectional Study), prior to data extraction. The serum BDNF analytic methods were reviewed in detail. RESULTS: A total of 2,148 potential studies were identified via the searches, of which 631 duplicates were removed, 1,488 abstracts were excluded for inappropriate population, outcome measure, or study design, and 29 articles were selected for full-text screening, with four studies included in the final review. All studies sampled and analyzed serum BDNF. A total of 271 participants (AIS: A-D, NLI: C1-L5), predominantly male (n = 224), with acute (n = 165) and chronic (n = 51) injuries aged 14-75 as well as healthy controls (n = 55) were included. One study investigated the influence of an intervention and three studies were cross-sectional. No identified study included a description or indication of the prevalence for MH conditions or CMD risk factors. CONCLUSIONS: Based on the reviewed literature, links between serum BDNF and MH disorders or CMD risk have not yet been established for individuals with acute or chronic tSCI. The selected studies demonstrated no consistent sampling or analysis methods, with limited adherence to prior established standards in the general population, bringing into question the reliability, validity, and quality of the available outcome data.