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The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

ABSTRACT: INTRODUCTION:Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. AIMS:We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. METHODS:In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). RESULTS:mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. CONCLUSIONS:Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE.

SUBMITTER: Sidhu MK

PROVIDER: S-EPMC6488925 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

Sidhu Meneka K MK Thompson Pamela J PJ Wandschneider Britta B Foulkes Alexandra A de Tisi Jane J Stretton Jason J Perona Marina M Thom Maria M Bonelli Silvia B SB Burdett Jane J Williams Elaine E Duncan John S JS Matarin Mar M

CNS neuroscience & therapeutics 20180627 2

<h4>Introduction</h4>Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups.<h4>Aims</h4>We examined whether BDNF Val66Met variatio ...[more]

PMID: 29952080

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Project description:BackgroundAlthough structural correlation network (SCN) analysis is an approach to evaluate brain networks, the neurobiological interpretation of SCNs is still problematic. Brain-derived neurotrophic factor (BDNF) is well-established as a representative protein related to neuronal differentiation, maturation, and survival. Since a valine-to-methionine substitution at codon 66 of the BDNF gene (BDNF Val66Met single nucleotide polymorphism (SNP)) is well-known to have effects on brain structure and function, we hypothesized that SCNs are affected by the BDNF Val66Met SNP. To gain insight into SCN analysis, we investigated potential differences between BDNF valine (Val) homozygotes and methionine (Met) carriers in the organization of their SCNs derived from inter-regional cortical thickness correlations.MethodsForty-nine healthy adult subjects (mean age = 41.1 years old) were divided into two groups according to their genotype (n: Val homozygotes = 16, Met carriers = 33). We obtained regional cortical thickness from their brain T1 weighted images. Based on the inter-regional cortical thickness correlations, we generated SCNs and used graph theoretical measures to assess differences between the two groups in terms of network integration, segregation, and modularity.ResultsThe average local efficiency, a measure of network segregation, of BDNF Met carriers' network was significantly higher than that of the Val homozygotes' (permutation p-value = 0.002). Average shortest path lengths (a measure of integration), average local clustering coefficient (another measure of network segregation), small-worldness (a balance between integration and segregation), and modularity (a representative measure for modular architecture) were not significantly different between group (permutation p-values ? 0.01).Discussion and conclusionOur results suggest that the BDNF Val66Met polymorphism may potentially influence the pattern of brain regional morphometric (cortical thickness) correlations. Comparing networks derived from inter-regional cortical thickness correlations, Met carrier SCNs have denser connections with neighbors and are more distant from random networks than Val homozygote networks. Thus, it may be necessary to consider potential effects of BDNF gene mutations in SCN analyses. This is the first study to demonstrate a difference between Val homozygotes and Met carriers in brain SCNs.

Dataset Information

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

Publications

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

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