Impact of brain-derived neurotrophic factor Val66Met polymorphism on cortical thickness and voxel-based morphometry in healthy Chinese young adults

Abstract

Background: Following voxel-based morphometry (VBM), brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been shown to affect human brain morphology in Caucasians. However, little is known about the specific role of the Met/Met genotype on brain structure. Moreover, the relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied.

Methodology/principal findings: The present study investigated brain structural differences among three genotypes of BDNF (rs6265) for the first time in healthy young Chinese adults via cortical thickness analysis and VBM. Brain differences in Met carriers using another grouping method (combining Val/Met and Met/Met genotypes into a group of Met carriers as in most previous studies) were also investigated using VBM. Dual-approach analysis revealed less gray matter (GM) in the frontal, temporal, cingulate and insular cortices in the Met/Met group compared with the Val/Val group (corrected, P<0.05). Areas with less GM in the Val/Met group were included in the Met/Met group. VBM differences in Met carriers were only found in the middle cingulate cortex.

Conclusions/significance: The current results indicated a unique pattern of brain morphologic differences caused by BDNF (rs6265) in young Chinese adults, in which the Met/Met genotype markedly affected the frontal, temporal, cingulate, and insular regions. The grouping method with Met carriers was not suitable to detect the genetic effect of BDNF Val66Met polymorphism on brain morphology, at least in the Chinese population, because it may hide some specific roles of Met/Met and Val/Met genotypes on brain structure.

Figure 1. Cortical thickness differences among three genotypes based on the BDNF Val66Met polymorphism.

Left panel: areas with a significantly thinning cortex in the Met/Met group compared with the Val/Val group (Met/Met < Val/Val, corrected, P<0.05). Right panel: areas with a significantly thinning cortex in the Val/Met group compared with the Val/Val group (Val/Met < Val/Val, corrected, P<0.05). cMFC, caudal middle frontal cortex; IC, insular cortex; IPC, inferior parietal cortex; LOC, lateral occipital cortex; MTC, middle temporal cortex; OFC, orbital frontal cortex; PC, precuneus cortex; PCC, posterior cingulate cortex; rMFC, rostral middle frontal cortex; SFC, superior frontal cortex; SPC, superior parietal cortex;. See Table 2 and Table 3 for details.

Figure 2. VBM differences among three genotypes based on the BDNF Val66Met polymorphism.

Top panel: areas with a significantly decreased GM volume in Met/Met group compared with Val/Val group (Met/Met < Val/Val, corrected, P<0.05). Bottom left panel: areas with a significantly decreased GM volume in the Val/Met group compared with the Val/Val group (Val/Met < Val/Val, corrected, P<0.05). Bottom left panel: areas with a significantly decreased GM volume in the Met carriers group (Met/Met+Val/Met) compared with the Val/Val group (Met carriers < Val/Val, corrected, P<0.05 ). ACC, anterior cingulate cortex; MCC, middle cingulated cortex; MTC, middle temporal cortex; IC, insular cortex; IFC, inferior frontal cortex; OFC, orbital frontal cortex; PCC, posterior cingulate cortex; STC, superior temporal cortex.