BackgroundsThis study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years. MethodsParticipants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset. ResultsOut of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months. LimitationsThe study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings. ConclusionsA significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors.