Preservation of general intelligence following traumatic brain injury: contributions of the Met66 brain-derived neurotrophic factor

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.

Figure 1. Lesion mapping results for Val/Val genotype patients (n = 97).

In each axial slice, the right hemisphere is on the reader’s left.

Figure 2. Lesion mapping results for Val/Met genotype patients (n = 59).

In each axial slice, the right hemisphere is on the reader’s left.

Figure 3. Lesion overlap map illustrating common and distinctive brain regions for Val/Val (blue) and Val/Met (yellow) genotype patients.

Overlap between Val/Val and Val/Met genotype patients is illustrated in green. In each axial slice, the right hemisphere is on the reader's left.

Figure 4. Summary of structural equation modeling results (n = 171).

Figure 5. Wechsler Adult Intelligence Scale latent scores.

g = general intelligence, VC = verbal comprehension, PO = perceptual organization, WM = working memory, PS = processing speed, * = p<0.05, ** = p<0.01.