Mature brain-derived neurotrophic factor (BDNF) levels in serum correlate with symptom severity in post-traumatic stress disorder (PTSD)

• The relationship between BDNF and PTSD symptom severity is currently unclear. • BDNF can be measured as general protein levels or mature protein only levels. • PTSD symptoms can be measured by clinician-scale (CAPS-5) or self-report (PCL-5). • Mature BDNF levels in serum correlate to CAPS-5 and PCL-5. • Stronger BDNF correlation detected to CAPS-5 than PCL-5. Post-traumatic stress disorder (PTSD) is characterised by pervasive and persistent symptoms that negatively impact quality-of-life. A relationship between brain-derived neurotrophic factor (BDNF) and PTSD symptom severity has been investigated with mixed results. This study aimed to systematically investigate BDNF and PTSD symptom severity in a PTSD cohort ( n = 43). BDNF levels were determined from both serum and plasma using two BDNF assays (targeting general BDNF and mature BDNF specifically). BDNF levels were compared to PTSD symptom severity scores determined by clinical interview using the Clinician-Administered PTSD Scale (CAPS-5) for DSM-5 and the self-rated Posttraumatic Stress Disorder checklist (PCL-5) for DSM-5. Only mature BDNF levels from serum revealed a significant negative correlation to both CAPS-5 and PCL-5 scores. Additionally, when the study cohort was defined by the CAPS-5 criteria for PTSD, the BDNF to symptom severity correlation was stronger than when the cohort was defined by the PCL-5 criteria. This study acknowledges that limited numbers of PTSD participants with complex co-morbidities and multiple test comparisons requires caution in overinterpretation of results. Overall, this study found that decreasing levels of mature BDNF from serum was associated with increasing symptom severity and that the type of sample, the specificity of the BDNF assay and the PTSD evaluation method all impacted whether a relationship between BDNF and PTSD symptom severity could be detected.