The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

Abstract

Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF) gene resulting in a valine (Val) to methionine (Met) substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18) and Met-allele carriers (n = 55). Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

“…Following the demonstration that this SNP was functionally relevant over the past 18 years, more than 1700 studies have investigated the effects of this polymorphism on brain function in health, as well as in diseases, particularly in neuropsychiatric disorders [ 115 , 116 ]. The BDNF Val66Met polymorphism has been associated with cerebral cortex plasticity [ 117 , 118 ], with gray matter structures [ 119 , 120 ], or white matter integrities and structural networks [ 121 , 122 ]. More specifically, BDNF Val66Met polymorphism is associated with cognitive processes [ 112 , 123 , 124 , 125 , 126 , 127 ], and cognitive impairment in neurodegenerative disease, such as Parkinson’s disease (PD) [ 128 , 129 ] and AD [ 130 , 131 ], and even more with several brain disorders, including MDD and bipolar disorder [ 132 , 133 , 134 , 135 , 136 , 137 ], epilepsy [ 138 , 139 , 140 ], schizophrenia [ 125 , 141 , 142 , 143 , 144 ], aging and dementia [ 145 ] and stroke [ 117 , 146 , 147 ].…”

Alterations in the connection topology of brain structural networks in Internet gaming addiction

“…For each individual’s brain structural network, attacks on nodes were simulated in two different ways 17 . In one way, targeted attacks were addressed by eliminating central nodes from the original network.…”

Contextual experience modifies functional connectome indices of topological strength and organization

“…Preferential or targeted removal of highly connected hub nodes can cause a sharp reduction in the size of the largest component, S, and reveal the critical point at which the network breaks into much smaller unconnected components (42,(54)(55)(56). Sharper or faster reductions in S as a function of the fraction of nodes present is indicative of a high reliance on hub nodes, which are central to overall network robustness (47).…”