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. 2017 Mar 9;10:44. doi: 10.3389/fnmol.2017.00044

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Copyright © 2017 Munoz, Kumar, Oh, Conley, Wang, Failla and Wagner.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Conceptual figure capturing biomarker relationships among younger individuals (≤48 years. Old, N = 90): (1) cortisol has a significant regulatory (mediating) effect on BDNF's influence on mortality, accounting for ~45% of BDNF's mortality effects; (2) the association between BDNF above/below the 75th percentile and high cortisol TRAJ is only significant among individuals with low BDNF secretion genotypes; and (3) the direct association between BDNF above/below the 75th percentile and mortality risk is stronger among individuals with the high BDNF secretion genotype (GRS = 0) compared to the low secretion genotypes. Taken together, the data support a conceptual model for younger individuals with TBI wherein high BDNF levels among those with high BDNF secretion phenotypes directly increases mortality risk, while mortality risk for those with high BDNF levels paired with low BDNF secretion genotypes is regulated (mediated) by cortisol.