Plasma BDNF shifts with sex, growth, and contact exposure in adolescent athletes
Plasma brain-derived neurotrophic factor is attracting attention as a possible biomarker for sport-related concussion, but baseline biology in healthy adolescent athletes is not uniform. In this Canadian cross-sectional study nested within a multi-site cohort, investigators measured plasma BDNF in 120 uninjured sport participants and then mapped those values against sex, age, concussion history, body size, menstrual cycle phase, and the type of sport played. The result is a reminder that a putative biomarker can be pulled in several directions before a head injury ever occurs.
Males had significantly higher plasma BDNF than females, with a beta estimate of 0.176 and a 95% confidence interval of 0.010 to 0.342. Contact sport participants also had lower BDNF than those in non-contact sports, with a beta estimate of –0.462 and a 95% confidence interval of –0.830 to –0.093. Those two associations alone complicate any attempt to use a single plasma threshold as a concussion readout across all adolescent athletes.
Why baseline biology matters before a concussion happens
BDNF is central to neuronal survival, synaptic plasticity, and activity-dependent brain adaptation. In the setting of concussion research, that makes it attractive: if neural injury alters BDNF dynamics, blood-based measurement could eventually contribute to diagnosis, risk stratification, or recovery monitoring. Yet the marker cannot be interpreted in isolation from development, sex biology, and repeated exposure to sport-related head impacts. A signal that changes with age or anthropometry can blur the difference between a normal adolescent baseline and a post-injury shift.
Here, sex and sport context were not background noise. They were part of the biology.
The cohort included 60 male participants with a mean age of 15.79 years and 60 female participants with a mean age of 15.97 years. Age was positively associated with BDNF in females only, with a beta estimate of 0.089 and a 95% confidence interval of 0.002 to 0.176. That pattern suggests that maturation may shape circulating BDNF differently in girls than in boys during mid-adolescence, a period when hormonal, skeletal, and neurodevelopmental trajectories do not progress in lockstep.
Height also tracked with BDNF. Greater height was associated with higher plasma levels, with a beta estimate of 0.011 and a 95% confidence interval of –0.001 to 0.021. By contrast, bodyweight and body mass index were not convincingly linked to BDNF in this analysis, and menstrual cycle phase did not show a significant association either. The lack of a meaningful menstrual phase effect does not erase sex-based differences, but it does suggest that circulating BDNF in this cohort was not simply a function of cycle timing at the level captured here.
Concussion history did not separate the baseline signal
Prior concussion history did not show a significant association with plasma BDNF. The beta estimate was –0.149, with a 95% confidence interval spanning –0.323 to 0.025 and a p value of 0.093. In practical terms, the biomarker did not clearly distinguish athletes with and without concussion history at baseline in this uninjured sample.
That finding is clinically important because it restrains the temptation to overread BDNF as a retrospective scar of prior brain injury. If a marker is meant to help identify sport-related concussion, it must remain interpretable against a background of pre-existing variation. Here, prior concussion history did not produce a clean separation, while sex, age in females, height, and sport type did.
The study design reinforces that point. This was a cross-sectional analysis, not a longitudinal injury-response experiment. It therefore cannot tell clinicians how BDNF changes immediately after concussion, how long any change persists, or whether the within-person delta differs from the between-person differences seen at baseline. It can, however, show what the baseline noise looks like before injury enters the picture.
Contact sport exposure may shape circulating BDNF before injury is diagnosed
The lower BDNF seen in contact sport athletes may reflect repeated subclinical head impacts, training load, or a broader physiologic adaptation to repeated collision exposure. The study does not prove mechanism, but the association is biologically plausible. Recurrent mechanical stress could influence neurotrophic signaling through repeated perturbation of neuronal and glial networks, with downstream effects on peripheral BDNF concentrations. Whether that represents a protective adaptation, a marker of cumulative exposure, or a transient response to recent participation remains unresolved.
This is where biomarker development becomes difficult. A valid concussion biomarker should ideally change because of injury, not because the athlete is older, taller, male, or plays a contact sport. The current data show that several of those baseline characteristics already move plasma BDNF in different directions. A diagnostic cutpoint built without accounting for them would be vulnerable to misclassification.
What this means for concussion biomarker research
Future studies of BDNF in sport-related concussion will need to control for participant characteristics with far more precision than a simple case-versus-control comparison. Sex, age, height, and sport classification should not be treated as peripheral covariates; they are part of the measurement environment. In adolescent athletes, that environment is especially dynamic because growth and maturation are still underway, and the biology of neurotrophins likely evolves alongside it.
The broader lesson is methodological rather than speculative. Before BDNF can be advanced as a clinically credible concussion biomarker, investigators will need longitudinal sampling, injury-linked trajectories, and careful stratification by developmental stage and sport exposure. Without that structure, the biomarker may remain difficult to interpret in the clinic, where the question is not whether a blood value is interesting, but whether it helps distinguish a concussed athlete from a healthy one on the sideline or in follow-up.
For now, the study narrows the field of interpretation. Plasma BDNF was higher in males, rose with height, increased with age in females, and was lower in contact sports. Prior concussion history did not clearly separate baseline levels. Those patterns make one thing plain: any future diagnostic use of BDNF will have to be built on the biology of the athlete first, and the injury second.