Abstract
Brain-derived neurotrophic factor (BDNF) promotes survival and synaptic plasticity in the human brain. The Val66Met polymorphism of the BDNF gene interferes with intracellular trafficking, packaging, and regulated secretion of this neurotrophin. The human prefrontal cortex (PFC) shows lifelong neuroplastic adaption implicating the Val66Met BDNF polymorphism in the recovery of higher-order executive functions after traumatic brain injury (TBI). In this study, we examined the effect of this BDNF polymorphism on the preservation of general intelligence following TBI. We genotyped a sample of male Vietnam combat veterans (n = 156) consisting of a frontal lobe lesion group with focal penetrating head injuries for the Val66Met BDNF polymorphism. Val/Met did not differ from Val/Val genotypes in general cognitive ability before TBI. However, we found substantial average differences between these groups in general intelligence (≈ half a standard deviation or 8 IQ points), verbal comprehension (6 IQ points), perceptual organization (6 IQ points), working memory (8 IQ points), and processing speed (8 IQ points) after TBI. These results support the conclusion that Val/Met genotypes preserve general cognitive functioning, whereas Val/Val genotypes are largely susceptible to TBI.
Highlights
Traumatic Brain Injury (TBI) is a global public health epidemic
The present study provides compelling evidence for a relationship between variations in the Val66Met brain-derived neurotrophic factor (BDNF) polymorphism and preservation of general intelligence after penetrating TBI
The Met allele had been found to be associated with relatively impaired cognitive functions in healthy individuals [11,13], stroke patients [42], psychiatric populations [43,44], and in patients recovering from mild TBI [45]
Summary
In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it results in motor and sensory deficits as well as severe cognitive, emotional, and psychosocial impairment. Despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. We build upon our prior work [1,2] by investigating the relationship between variations in the BDNF gene and preservation of general intelligence in the prefrontal cortex (PFC) after TBI. Damage to the PFC leads to impairment in executive function, which normally allows individuals to effectively engage in complex goal-directed behaviors, whereas the domains of perception and language are more often preserved [3]
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