BDNF polymorphism and inter hemispheric balance of motor cortex excitability: a preliminary study

Preclinical studies have demonstrated that Brain-Derived Neurotrophic Factor (BDNF) plays a crucial role in the homeostatic regulation of cortical excitability and excitation/inhibition balance. Using transcranial magnetic stimulation (TMS) techniques we investigated whether BDNF polymorphism could influence cortical excitability of the left and right primary motor cortex in healthy humans. Twenty-nine participants were recruited and genotyped for the presence of the BDNF Val66Met polymorphism, namely homozygous for the valine allele (Val/Val), heterozygotes (Val/Met), and homozygous for the methionine allele (Met/Met). Blinded to the latter, we evaluated inhibitory and facilitatory circuits of the left (LH) and right motor cortex (RH) by measuring resting (RMT) and active motor threshold (AMT), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). For each neurophysiological metric we also considered the inter-hemispheric balance expressed by the Laterality Index (LI). Val/Val participants (n= 21) exhibited an overall higher excitability of the LH compared to the RH, as probed by lower motor thresholds, lower SICI and higher ICF. Val/Val participants displayed positive LI, especially for AMT and ICF (all p< 0.05), indicating higher LH excitability and more pronounced inter-hemispheric excitability imbalance as compared to Met carriers. Our preliminary results suggest that BDNF Val66Met polymorphism might influence interhemispheric balance of motor cortex excitability.

Associations of the BDNF Val66Met Polymorphism With Body Composition, Cardiometabolic Risk Factors, and Energy Intake in Youth With Obesity: Findings From the HEARTY Study

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein (p = 0.01) and fat (p = 0.05) intake, C-Reactive protein (p = 0.05), and a trend toward higher overall energy intake (p = 0.07), fat-free mass (p = 0.07), and lower HDL-C (p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence.Clinical Trial Registration:http://clinicaltrials.gov/, identifier NCT00195858.

Interactions of Dietary Insulin Index and Dietary Insulin Load with BDNF Val66Met Polymorphism in Relation to Cardiometabolic Markers in Iranian Diabetic Patients: A Cross-Sectional Study

The progression of cardiometabolic diseases is determined by both genetic and environmental factors. Gene-diet interactions may therefore be important in modulating the risks of developing metabolic diseases. The objectives were to investigate the effect of the interaction between BDNF Val66Met polymorphisms and Dietary Insulin Index and Insulin Load (DII and DIL) on Cardiometabolic Markers among diabetic patients. In this cross-sectional study, blood samples were collected from 667 patients. DIL & DII were defined using a validated food frequency questionnaire (FFQ). Genotyping the BDNF Val66Met polymorphism was conducted by the PCR-RFLP method. Interactions between dietary indices and gene variants were evaluated using a Generalized Linear Model (GLM). PGF2a concentrations were significantly higher among Val homozygotes than Met alleles carrier. This study revealed that, compared with individuals with the Val/Val genotype, those with the Met/Val or Met/Met genotype had lower BMI (P-interaction =0.04), TG (P-interaction=0.04), leptin (P-interaction =0.01), LDL (P-interaction=0.04) and TC (P-interaction =0.01) when they consumed diets higher on the DIL index. Moreover, the highest quartile of the DIL, compared to the lowest, showed increased in WC (P-interaction =0.02) and LDL/HDL (P-interaction =0.04) for Val/Val homozygotes compared to Met-allele carriers. BDNF Val66Met variants may interact with DIL and DII, thus be involved in the development of cardiometabolic risk factors. If diabetic patients with Met alleles regulate dietary intakes, they have a protective opportunity to regulate their cardiometabolic markers.

The association between BDNF levels and risperidone-induced weight gain is dependent on the BDNF Val66Met polymorphism in antipsychotic-naive first episode schizophrenia patients: a 12-week prospective study

A growing number of studies have shown that brain-derived neurotrophic factor (BDNF) is associated with weight gain during antipsychotic treatment in schizophrenia patients. However, there is still a lack of research results in the initial stage of antipsychotic treatment. This study aimed to evaluate the relationship between weight gain caused by risperidone monotherapy for 12 weeks and BDNF level in antipsychotic-naive and first-episode (ANFE) patients with schizophrenia, and we hypothesize that this may depend on BDNF Val66Met gene polymorphism. In a 12-week longitudinal trial, 225 ANFE patients were enrolled and treated with risperidone. Body weight was measured at baseline and during the 12-week follow-up. After treatment, the average weight of ANFE patients increased by 2.6 kg. Furthermore, we found that in patients with Val/Val genotype, the increase in serum BDNF levels was negatively correlated with risperidone-induced weight gain (r = −0.44, p = 0.008). Regression analysis showed that the baseline BDNF level was a predictor of weight gain after treatment (β = −0.45, t = −3.0, p = 0.005). Our results suggest that the BDNF signaling may be involved in weight gain caused by risperidone treatment. Furthermore, the negative association between weight gain and increased BDNF levels during risperidone treatment in ANFE schizophrenia depends on the BDNF Val66Met polymorphism.