Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

Abstract

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder (BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray (GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P ¼ 0.01, right P ¼ 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P ¼ 0.01) and healthy groups (left P ¼ 0.03, right P ¼ 0.03). The Val/ Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (Po0.01). There was a significant main effect of diagnosis on memory function (P ¼ 0.04), but no interaction between diagnosis and genotype was found (P ¼ 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD.

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

“…The smaller hippocampal volumes in the Val66Met BDNF polymorphism detected in this meta-analysis have been also found in some (Pezawas et al 2004;Matsuo et al 2009;Schofield et al 2009), but not other (Ho et al 2006;Nemoto et al 2006;Joffe et al 2009;Montag et al 2009) studies using voxel-based morphometry. Converging lines of evidence from basic science as well as clinical studies further corroborate the effects of Val66Met BDNF polymorphism on hippocampal volumes.…”

BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects

“…However, the influence of BDNF on brain structure and function was also observed in different cortical regions (Pezewas et al 2004, Matsuo et al 2009, Yang et al 2012). In our study we concentrated on the relation between BDNF polymorphisms and haplotypes with neuropsychological measures engaging predominantly prefrontal cortex, an area associated with higher cognitive functions, such as working memory, executive attention, planning, set-shifting (Bath and Lee 2006).…”

“…Some research found BDNF genetic effect on cognition to be gender-specific (Matsuo et al 2009, Raz et al 2009, van Wingen et al 2010, Laing et al 2012). In our study the relation between BDNF polymorphisms and TMT_A performance was not modified by gender.…”

Influence of Brain-Derived Neurotrophic Factor Genetic Polymorphisms on the Ages of Onset for Heroin Dependence in a Chinese Population

“…Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin superfamily (Matsuo et al, 2009), promotes neuronal survival, and regulates the proliferation and differentiation of nerve cells in the peripheral and central nervous systems (Hartmann et al, 2001). BDNF serves an important role during brain development and in synaptic plasticity (Yang et al, 2009).…”