Polymorphisms in the Brain-Derived Neurotrophic Factor Gene Influence Memory and Processing Speed One Month after Brain Injury

Abstract

Brain-derived neurotrophic factor (BDNF) plays a role in cognition, as well as neural survival and plasticity. There are several common polymorphisms in the BDNF gene, one of which (rs6265) is an extensively studied non-synonymous coding polymorphism (Val66Met) which has been linked to cognitive performance in healthy controls and some clinical populations. We hypothesized that the Met allele of rs6265 would be associated with poorer cognitive performance in individuals with mild-to-moderate traumatic brain injury, and that other polymorphisms in the BDNF gene would also affect cognition. Genotype at 9 single-nucleotide polymorphisms (SNPs) in the BDNF gene, and measures of speed of information processing, learning, and memory were assessed in 75 patients with mTBI and 38 healthy subjects. Consistent with previous reports, the Met allele of rs6265 was associated with cognition (slower processing speed) in the entire group. Two other SNPs were associated with processing speed in the mTBI group, but both are in linkage disequilibrium with rs6265, and neither remained significant after adjustment for rs6265 status. Within the mTBI group, but not the controls, 4 SNPs, but not rs6265, were associated with memory measures. These associations were not affected by adjustment for rs6265 status. Polymorphisms in BDNF influence cognitive performance shortly after mTBI. The results raise the possibility that a functional polymorphism other than rs6265 may contribute to memory function after mTBI.

Outcome Prediction after Mild and Complicated Mild Traumatic Brain Injury: External Validation of Existing Models and Identification of New Predictors Using the TRACK-TBI Pilot Study

“…Emerging technologies that could improve prognostication in mTBI include proteomic biomarkers, [31][32][33] genetic factors, [34][35][36] and improved imaging biomarkers, including magnetic resonance imaging. 37 Additionally, prediction models for mTBI may require moresensitive and -specific outcome measures beyond the GOS-E.…”

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

“…110,115 The APOE genotype is not neces sarily a non-modifiable risk factor for concussion recovery: therapies being developed for AD include drugs that modify the interaction between the ApoE4 protein and Aβ, which might also be applicable to paediatric concussion. 116,117 Other genetic risk factors The Val66Met polymorphism in the gene encoding brain-derived neurotrophic factor has been linked to better outcomes after mTBI, 118 but worse outcomes after focal penetrating brain injury. 119 Polymorphisms in genes involved in dopaminergic signalling may also help to account for the wide range of TBI outcomes.…”

Impact of traumatic brain injury on sleep structure, electrocorticographic activity and transcriptome in mice

“…Research has shown that some of these elements may guide regrowth of damaged neurons in developed organisms (Deister and Schmidt, 2006). One such element is brain-derived neurotrophic factor (BDNF) that seems to profit brain recovery after TBI (McAllister et al, 2012;Rostami et al, 2011). The expression of plasticity genes such as Bdnf, Homer1a and Fos or of their protein product is increased in the hippocampus and cortex during the first hours after mTBI (Abrous et al, 1999;Colak et al, 2012;Crack et al, 2009;Hicks et al, 1999).…”