Effects Of BDNF Val66Met Polymorphism Research Articles

Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations.

Objective The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD. Methods Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics. Results The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II. Conclusion Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

Interaction between BDNF val66met polymorphism and personality on long-term cardiac outcomes in patients with acute coronary syndrome.

BackgroundThe prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.MethodsA total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.ResultsThe BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.ConclusionsGene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

MARKERS AND BIOMARKERS OF DEMENTIA BDNF GENOTYPE AND CHANGES IN WHITE MATTER HYPERINTENSITIES AND HIPPOCAMPAL MICROSTRUCTURE IN OLDER MEN AND WOMEN

Brain-derived neurotrophic factor (BDNF) may protect against cerebral gray and white matter impairments in older age. The val66met genetic polymorphism of BDNF is recently emerging as an early marker of brain structural integrity. However, evidence is sparse, cross-sectional, and mostly in men. In a longitudinal cohort study of community-dwelling older adults (N=139, mean age=81.6, 58% female, 58% white, mean follow-up=3.4 years), we estimated the overall and sex-stratified effects of BDNF val66met polymorphism on changes in cognition and gray and white matter macro- and micro-structure. Annualized percent change was computed for volume of white matter (WM) hyperintensities and gray matter (GM), fractional anisotropy of normal appearing WM, and mean diffusivity (MD) of GM in whole brain and memory and executive control function networks. Significant associations were adjusted for variables differing by genotype (race, APOE4, diabetes, triglycerides, smoking). Compared to met carriers, val homozygotes had slower annual whole brain WMH accrual (median (IQR) 31.4% (61.7) vs. 60.7% (92.4)), stronger in women. Met carriers had slower annual accrual of hippocampal MD (median (IQR) 1.26% (0.92) vs. 1.85% (1.09) for right hippocampus, stronger for women, and 1.45% (1.06) vs. 1.97% (1.22) for left hippocampus, stronger for men) compared to val homozygotes. Associations were robust to covariates’ adjustment. BDNF polymorphism was not associated with cognitive changes. BDNF polymorphism may help in early identification of those more likely to resist accrual of WMH and loss of hippocampal microstructural integrity, with effects varying by sex.

Dosage Effects of BDNF Val66Met Polymorphism on Cortical Surface Area and Functional Connectivity

The single nucleotide polymorphism (SNP) that leads to a valine-to-methionine substitution at codon 66 (Val66Met) in BDNF is correlated with differences in cognitive and memory functions, as well as with several neurological and psychiatric disorders. MRI studies have already shown that this genetic variant contributes to changes in cortical thickness and volume, but whether the Val66Met polymorphism affects the cortical surface area of healthy subjects remains unclear. Here, we used multimodal MRI to study whether this polymorphism would affect the cortical morphology and resting-state functional connectivity of a large sample of healthy Han Chinese human subjects. An SNP-wise general linear model analysis revealed a "dosage effect" of the Met allele, specifically a stepwise increase in cortical surface area of the right anterior insular cortex with increasing numbers of the Met allele. Moreover, we found enhanced functional connectivity between the anterior insular and the dorsolateral prefrontal cortices that was linked with the dosage of the Met allele. In conclusion, these data demonstrated a "dosage effect" of BDNF Val66Met on normal cortical structure and function, suggesting a new path for exploring the mechanisms underlying the effects of genotype on cognition.

Effect of BDNF Val66Met Polymorphism on Normal Variability of Executive Functions

Associations of BDNF Val66Met polymorphism with such components of executive functions as verbal fluency, working memory, attention set shifting, and response inhibition were evaluated. A total of 401 healthy volunteers were genotyped. The effect of polymorphism on working memory during the counting test was detected. The test performance in heterozygotic carriers was much worse than in homozygotic ones. Individuals with the MetMet genotype demonstrated the best results, presumably due to molecular mechanisms compensating for the neuropeptide secretion deficiency.

Effects of BDNF Val66Met polymorphism on brain metabolism in Alzheimer's disease

Earlier studies showed that the Val66Met polymorphisms of the brain-derived neurotrophic factor differentially affect gray matter volume and brain region activities. This study used resting positron emission tomography to investigate the relationship between the polymorphisms of Val66Met and the regional cerebral metabolic rate in the brain. We analyzed the positron emission tomography images of 215 patients from the Alzheimer's Disease Neuroimaging Initiative and found significant differences in the parahippocampal gyrus, superior temporal gyrus, prefrontal cortex, and inferior parietal lobule when comparing Met carriers with noncarriers among both the normal controls and those with mild cognitive impairment. For those with Alzheimer's disease, we also found additional differences in the bilateral insula between the carriers and noncarriers.

Interaction effects between COMT and BDNF polymorphisms on boredom susceptibility of sensation seeking traits

Sensation seeking is a temperament associated with willingness to take risks to obtain arousal. We investigated the relationship between the polymorphisms of the COMT Val158Met and BDNF Val66Met and sensation seeking traits. The Sensation Seeking Scale (SSS) and genotyping were performed in 277 Korean healthy volunteers (165 males, 112 females). Multivariate analysis of covariance was used to test the association between the COMT and BDNF functional polymorphisms and dimensions of sensation seeking, namely, disinhibition, boredom susceptibility, experience seeking and thrill/adventure seeking. No main and interaction effects of the COMT and BDNF on SSS were observed for total subjects. However, in females, a significant gene–gene interaction effect on the boredom susceptibility of SSS was shown. Among females with COMT Met present genotype (Val/Met + Met/Met), subjects with BDNF Met absent genotype (Val/Val) had significantly higher boredom susceptibility than subjects with BDNF Met. The effects of BDNF Val66Met polymorphism on boredom susceptibility of sensation seeking traits could be modulated by COMT Val158Met polymorphism in female.