Effects of the BDNF Val66Met Polymorphism on White Matter Microstructure in Healthy Adults

Abstract

The BDNF Val 66 Met polymorphism, a possible risk variant for mental disorders, is a potent modulator of neural plasticity in humans and has been linked to deficits in gray matter structure, function, and cognition. The impact of the variant on brain white matter structure, however, is controversial and remains poorly understood. Here, we used diffusion tensor imaging to examine the effects of BDNF Val 66 Met genotype on white matter microstructure in a sample of 85 healthy Caucasian adults. We demonstrate decreases of fractional anisotropy and widespread increases in radial diffusivity in Val/Val homozygotes compared with Met-allele carriers, particularly in prefrontal and occipital pathways. These data provide an independent confirmation of prior imaging genetics work, are consistent with complex effects of the BDNF Val 66 Met polymorphism on human brain structure, and may serve to generate hypotheses about variation in white matter microstructure in mental disorders associated with this variant.

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…Genetic variants of the BDNF gene associated with schizophrenia (Neves-Pereira et al, 2005) produce progressive cortical and hippocampal structural changes, as well as behavioral impairment (Egan et al, 2003a;Pezawas et al, 2004). A genetic variant of BDNF associated with increased risk for psychiatric disorders including schizophrenia (Egan et al, 2003b;Gratacos et al, 2007) is linked to reduced cortical and hippocampal volumes and impaired learning and memory, presumably by interfering with the development and maintenance of neurons and synapses (Egan et al, 2003b;Eisenberg et al, 2013;Hariri et al, 2003;Pezawas et al, 2004;Szeszko et al, 2005;Tost et al, 2013). However, these findings are not always replicated and more studies are needed to clarify the mechanisms of the Val66Met allele and psychiatric illness (Kanazawa et al, 2007).…”

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive–compulsive disorder

“…While genetic polymorphisms have been associated with WM microstructure in healthy individuals (Braskie et al, , 2013Tost et al, 2013), others have been exclusively associated in patients suffering from different mental disorders (Mounce et al, 2014;Seok et al, 2013). The influence on WM microstructure of the genetic variants associated in the present study had not been previously studied.…”

“…Results from studies that have assessed BDNF (Fontenelle et al, 2012;Maina et al, 2010;Y Wang et al, 2011) and NGF (Fontenelle et al, 2012) levels in patients with OCD showed lower and higher protein levels compared with healthy controls, respectively. Genetic variants encoding neurotrophins and their receptors have shown an effect on WM microstructure in healthy subjects (Braskie et al, , 2013Tost et al, 2013) and also in patients with major depression (Carballedo et al, 2012). Cadherins mediate cell-cell adhesion and are involved at all levels of functional brain specification, from early embryonic patterning to circuit formation, synaptogenesis and synaptic plasticity in the mature brain.…”

“…However, genetic markers in genes involved in the dopaminergic (COMT), glutamatergic (GRM3) and neurotrophic (BDNF, NTRK1 and NTRK3) pathways have been recently associated with this WM microstructure measure in healthy subjects and also in patients with schizophrenia or major depression (Braskie et al, , 2013Carballedo et al, 2012;Kohannim et al, 2012;Mounce et al, 2014;Seok et al, 2013;Tost et al, 2013).…”

White and gray matter contributions to executive function recovery after traumatic brain injury

“…Interestingly, the Val variant of the BDNF gene is associated with reduced white matter integrity in healthy participants, 38 while Met allele carriers demonstrate increased structural connectivity, 39 despite the greater association of the Met allele with cognitive impairment and clinical pathology. 40 It would be interesting to study whether individual genetic variation mediates the contribution of white matter structural integrity in functional outcome after brain injury.…”