OBJECTIVE:Mild traumatic brain injuries (mTBIs) have frequently been associated with the emergence and persistence of depressive symptoms. However, the factors which contribute to the increased risk for depression after these head injuries remain unclear. Accordingly, we examined the relationship between frequency of self-reported mTBIs and current symptoms of depression and the mediating role of rumination and cognitive flexibility. We also examined whether these relations were moderated by sex differences and the presence of the Val66Met polymorphism in a gene coding for brain-derived neurotrophic factor (BDNF). DESIGN:Retrospective, cross-sectional. SETTING:Carleton University. PARTICIPANTS:Two hundred nineteen Carleton University undergraduate students. MAIN OUTCOME MEASURES:Cognitive flexibility as assessed by the Wisconsin Card Sorting Task (WCST); subtypes of rumination (Ruminative Response Scale; Treynor, Gonzalez, and Nolen-Hoeksema, 2003); depressive symptoms (Beck Depression Inventory; Beck, Ward, and Mendelson, 1961). RESULTS:Greater frequency of self-reported mTBIs was associated with more frequent depressive rumination among women, but not men, which was accompanied by elevated current depressive symptoms. In addition, among Met allele carriers of the BDNF polymorphism, but not those who were Val homozygotes, greater frequency of mTBIs was related to higher levels of brooding, which was accompanied by heightened depressive symptoms. Brain-derived neurotrophic factor genotype also moderated the relationship between self-reported mTBIs and cognitive flexibility in that more frequent mTBIs were associated with more perseverative errors on the WCST among Met carriers, but not Val homozygotes. CONCLUSIONS:The present findings raise the possibility that the evolution of depression after mTBIs may be dependant on a BDNF polymorphism and sex differences.