Brain-derived Neurotrophic Factor Rs6265 Polymorphism Research Articles

The relationship between the rs6265 polymorphism of the BDNF gene and the level of serum neurotrophic factor in patients with Parkinson's disease

To evaluate the clinical features and the level of serum brain-derived neurotrophic factor (BDNF) in groups of patients with Parkinson's disease (PD) differentiated by the genotypes of BDNF polymorphism (rs6265). The level of serum BDNF in the biomarkers' multiplex panel of neurodegenerative diseases (HNDG3MAG-36K) was assessed in 134 PD patients. Allele discrimination was carried out by real-time PCR using TaqMan probes for the analysis of BDNF rs6265 polymorphism in groups of patients and controls (n=192) matched for sex, age and ethnicity. Comparing the distribution of rs6265 genotypes and alleles between groups of patients and controls no significant differences were found (p>0.05). Serum BDNF levels varied significantly by genotype (rs6265) among PD patients. Minimum mean serum BDNF level (320.1±164.6 pg/ml) was noted for individuals with the AA genotype, which significantly differs from the corresponding indicator among individuals with GA (2944.2±1590.6 pg/ml; p=0.0001) and GG genotypes (2949.4±1620.6 pg/ml; p=3.9×10-5). The concentration of BDNF significantly differed between patients with different forms of PD (p=0.0007) and increased as the stage of the disease progressed according to Hoehn and Yahr staging scale (p=1.0×10-6). The BDNF rs6265 polymorphism was not associated with the development of PD in the studied population. The variability of the mean serum BDNF level was established depending on the genotype of the BDNF polymorphism in PD patients and a number of clinical features.

Association of the G>A (rs6265) polymorphism in the brain derived neurotrophic factor gene (BDNF) with post-training changes in Caucasian women

The brain-derived neurotrophic factor (BDNF) rs6265 (G196A; Val66Met) polymorphism has been associated with obesity and type 2 diabetes, with contradictory results involving either A or G as the risk allele. The main aim of this study was to examine whether the BDNF rs6265 polymorphism would influence the efficiency of a training program. An additional aim was to determine whether selected polymorphism can be used as a genetic marker for obesity-related parameters. We studied the genotype distribution in a group of 160 Caucasian females in whom body mass and composition parameters, lipid profile, and glucose levels were measured before and after the 12-week aerobic training program. The majority of obesity-related parameters significantly changed during the intervention (main effect of training); however, the training response was not modulated by genotype (non-significant genotype × training interactions). We also did not find an effect of genotype on selected parameters. Our study showed that the rs6265 polymorphism does not affect the efficiency of the applied training program and is not a good genetic marker for assessing the obesity-related parameters in the studied population. However, we confirmed that regular physical activity is associated with an improvement in obesity-related parameters, which is an important observation for public health.

Brain-Heart Axis: Brain-Derived Neurotrophic Factor and Cardiovascular Disease-A Review of Systematic Reviews.

The brain-heart axis is an intra- and bidirectional complex that links central nervous system dysfunction and cardiac dysfunction. In recent decades, brain-derived neurotrophic factor (BDNF) has emerged as a strategic molecule involved in both brain and cardiovascular disease (CVD). This systematic review of systematic reviews aimed to (1) identify and summarize the evidence for the BDNF genotype and BDNF concentration in CVD risk assessment, (2) evaluate the evidence for the use of BDNF as a biomarker of CVD recovery, and (3) evaluate rehabilitation approaches that can restore BDNF concentration. A comprehensive search strategy was developed using PRISMA. The risk of bias was assessed via ROBIS. Seven studies were identified, most of which aimed to evaluate the role of BDNF in stroke patients. Only two systematic reviews examined the association of BDNF concentration and polymorphism in CVDs other than stroke. The overall evidence showed that BDNF plays a fundamental role in assessing the risk of CVD occurrence, because lower BDNF concentrations and rs6265 polymorphism are often associated with CVD. Nevertheless, much work remains to be carried out in current research to investigate how BDNF is modulated in different cardiovascular diseases and in different populations.

Brain-Derived Neurotrophic Factor rs6265 polymorphism is associated with severe cancer-related fatigue and neuropathic pain in female cancer survivors

PurposeThis study examined the relationships between a single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) rs6265 and psychoneurological (PN) symptoms in female cancer survivors.MethodsThis secondary analysis examined 393 study participants. In addition to demographic variables, self-reported PN symptom scores (anxiety, bodily pain, depression, fatigue, neuropathic pain, and sleep disturbance) were collected using the Patient-Reported Outcomes Measurement Information System and 36-Item Short-Form Health Survey. Buccal swab samples were collected to obtain genotypes for BDNF rs6265 (Val/Val, Val/Met, or Met/Met). The PN symptom scores were compared across genotypes, and the relationships were examined using a regression model. We also explored correlations between different symptoms within each genotype.ResultsParticipants with the Met/Met genotype reported significantly worse cancer-related fatigue and neuropathic pain, which was confirmed by rank-based regression analysis. In addition, cancer-related fatigue was correlated with other PN symptoms, particularly depression. These correlations were stronger in study participants with the Met/Met genotype than those with other genotypes.ConclusionOur study suggests that female cancer survivors with the Met/Met genotype of BDNF rs6265 are likely to experience worse cancer-related fatigue and neuropathic pain and that cancer-related fatigue is a good predictor of co-occurring PN symptoms in this population.Implications for Cancer SurvivorsOur findings advance the scientific community's understanding of cancer-related PN symptoms experienced by female cancer survivors, especially the unique role of BDNF rs6265 polymorphism in these symptoms. Our findings offer valuable insights for clinical practice that the symptom experience among female cancer survivors may vary based on BDNF genotypes.

Brain-derived neurotrophic factor Val66Met polymorphism moderates the relationship between impulsivity, negative emotions, and binge drinking intensity in university students.

Studies on the genetic factors involved in binge drinking (BD) and its associated traits are very rare. The aim of this cross-sectional study was to investigate differences in the association between impulsivity, emotion regulation and BD in a sample of young adults according to the rs6265/Val66Met variant in the brain-derived neurotrophic factor (BDNF) gene, a well-known candidate gene in alcohol use disorders. We recruited 226 university students (112 women), aged between 18 and 25years old, from two centers in France. The participants completed measures related to alcohol consumption, depression severity, state anxiety levels, impulsivity (UPPS-P), and difficulties in emotion regulation [Difficulty in Emotion Regulation Scale (DERS)]. The relationship between the BD score and the clinical characteristics in the BDNF genotype groups was assessed by partial correlation analyses and moderation analyses. The partial correlation analyses showed that, in the Val/Val genotype group, the BD score was positively related to UPPS-P Lack of Premeditation and Sensation Seeking scores. In the Met carriers group, the BD score was positively related to UPPS-P Positive Urgency, lack of Premeditation, lack of Perseverance and Sensation Seeking scores and to Clarity score of the DERS. Moreover, the BD score was positively associated with depression severity and state anxiety scores. The moderation analyses revealed that BDNF Val/Met genotype moderated the relationship between several clinical variables and BD. The results of the present study support the hypothesis of common and specific vulnerability factors regarding impulsivity and emotion regulation difficulties associated with BD according to this BDNF rs6265 polymorphism.

BDNF rs6265 differentially influences neurometabolites in the anterior cingulate of healthy and bipolar disorder subjects.

Brain-derived neurotrophic factor (BDNF) is the most abundant brain neurotrophin and plays a critical role in neuronal growth, survival and plasticity, implicated in the pathophysiology of Bipolar Disorders (BD). The single-nucleotide polymorphism in the BDNF gene (BDNF rs6265) has been associated with decreased hippocampal BDNF secretion and volume in met carriers in different populations, although the val allele has been reported to be more frequent in BD patients. The anterior cingulate cortex (ACC) is a key center integrating cognitive and affective neuronal connections, where consistent alterations in brain metabolites such as Glx (Glutamate + Glutamine) and N-acetylaspartate (NAA) have been consistently reported in BD. However, little is known about the influence of BDNF rs6265 on neurochemical profile in the ACC of Healthy Controls (HC) and BD subjects. The aim of this study was to assess the influence of BDNF rs6265 on ACC neurometabolites (Glx, NAA and total creatine- Cr) in 124 euthymic BD type I patients and 76 HC, who were genotyped for BDNF rs6265 and underwent a 3-Tesla proton magnetic resonance imaging and spectroscopy scan (1H-MRS) using a PRESS ACC single-voxel (8cm3) sequence. BDNF rs6265 polymorphism showed a significant two-way interaction (diagnosis × genotype) in relation to NAA/Cr and total Cr. While met carriers presented increased NAA/Cr in HC, BD-I subjects with the val allele revealed higher total Cr, denoting an enhanced ACC metabolism likely associated with increased glutamatergic metabolites observed in BD-I val carriers. However, these results were replicated only in men. Therefore, our results support evidences that the BDNF rs6265 polymorphism exerts a complex pleiotropic effect on ACC metabolites influenced by the diagnosis and sex.

Brain‐derived Neurotrophic Factor in Duchenne Muscular Dystrophy Myopathy

Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are crucial for neuronal growth and survival, and loss of this signaling nexus invariably leads to neurodegeneration. In a small cohort of Duchenne muscular dystrophy (DMD) patients we found that BDNF blood levels positively correlated with better heart function, and carriers of the common BDNF single nucleotide polymorphism rs6265 (Val66‐Met) exhibited significantly worse skeletal muscle function and earlier loss of ambulation, compared to non‐carriers. We thus hypothesized that BDNF/TrkB signaling delays progression of myopathy in DMD. To test this hypothesis, we administered the TrkB agonist 7,8‐dihydroxyflavone (DHF) to mdx mice in their drinking water for 26 weeks, beginning at 8 weeks of age. Based on functional assessment using the hang test, DHF treatment preserved skeletal muscle function compared to vehicle‐treated controls. Trichrome staining of gastrocnemius and cardiac tissues also showed reduced levels of fibrosis, which correlated with BDNF expression levels. Using humanized BDNF polymorphic mice, which have the Val66‐Met mutation, and mice with a point mutation in the equivalent position of murine BDNF (Val68‐Met), we found that skeletal muscle strength was significantly reduced in mice with the Met allele, compared to Val/Val littermate controls. Although Val/Met and Met/Met mice weighed considerably more than control mice, they exhibited significantly increased activity, as measured by voluntary wheel running. Based on transmission electron microscopy, individual gastrocnemius muscle fibers of Met/Met mice were smaller and less organized compared to those of Val/Val. Finally, we crossed Val66‐Met mice with mdx mice to assess the effects of the BDNF polymorphism on the dystrophic background. As was found for DMD patients who harbor the BDNF rs6265 polymorphism, dystrophic mice with the Met allele exhibited worse skeletal muscle function compared to noncarriers. Considered together, our results indicate that BDNF plays a protective role in dystrophic muscle and might represent a novel therapeutic candidate for DMD myopathy.

Low-dose ketamine infusion for treating subjective cognitive, somatic, and affective depression symptoms of treatment-resistant depression.

Whether the antidepressant effects of low-dose ketamine infusion and the therapeutic impact of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism vary across different depression symptom domains, namely affective, cognitive, and somatic, remains unclear. We-reanalyzed the data of Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression (TRD). A total of 71 patients with TRD were randomized to three infusion groups: 0.5 and 0.2mg/kg ketamine groups and the normal saline placebo group. The Beck Depression Inventory-II (BDI-II) was used to obtain self-reported scores prior to infusion and 240min after infusion and sequentially on days 3, 7, and 14 after infusion. The three-factor model of cognitive, somatic, and affective depressive symptoms that is based on the BDI-II and proposed by Beck et al. was applied in the current study. The Val66Met BDNF polymorphism was genotyped. Ketamine infusion exerted rapid and sustained antidepressant effects on the affective (p=0.014) and cognitive (p=0.005) depression symptom domains but not on the somatic (p=0.085) depression symptom domain. Only patients with TRD harboring any Val allele at the BDNF rs6265 polymorphism were more likely to respond (p=0.011) to low-dose ketamine infusion. Additional studies should elucidate different mechanisms underlying the effects of ketamine infusion on cognitive, affective, and somatic depression symptom domains in patients with TRD.

Genetic association between bone mineral density and the fracture of distal radius: A case-control study.

Low bone mineral density (BMD) was significantly related to the fracture of distal radius. Serum brain-derived neurotrophic factor (BDNF) level was closely related to BMD in spine and osteoporotic fractures. In this study, we aimed to explore the association of BDNF polymorphisms (rs6265 and rs7124442) with BMD and the fracture of distal radius.This retrospective study included 152 patients with distal radius fractures and 148 healthy controls. BDNF polymorphisms were detected via TaqMan allelic discrimination assay. BMD was evaluated through X-ray. Difference in features between cases and controls were compared adopting Chi-square test or t test. The associations of BDNF polymorphisms with fracture risk of distal radius and BMD were assessed employing χ2 test and expressed by odd ratios (ORs) with 95% confidence intervals (95% CIs).BMD was significantly decreased in patients with the fracture of distal radius than in healthy controls. The polymorphism rs6265 significantly increased the risk of distal radius fracture (adjustment: GA: OR = 1.724, 95%CI = 1.003 –2.951, P = .049; GG: OR = 2.415, 95%CI = 1.0219 –3.674, P = .005). Moreover, rs6265 genotypes GA (OR = 4.326, 95%CI = 1.725 –11.896, P = .003) and GG (OR = 13.285, 95%CI = 3.659 –51.072, P = .001) significantly increased BMD reduction. However, BDNF polymorphism rs7124442 had no obvious correlation with BMD or fracture risk.BMD was associated with BDNF rs6265 polymorphism. BDNF polymorphism rs6265 could elevate the risk of osteoporosis and distal radius fracture.

The BDNF rs7934165 polymorphism is a biomarker of central obesity and cardiometabolic risk in Mexican women.

Brain-derived neurotrophic factor (BDNF) is a cornerstone in the hypothalamic regulation of food intake and energy homeostasis. Polymorphisms in the BDNF gene may thus contribute to obesity traits. The aim of this investigation was to analyze the association of rs6265 and rs7934165 BDNF polymorphisms in women from Northeast Mexico classified as obese or overweight using their BMI and waist-to-height ratio (WHtR). A total of 296 women were enrolled and further divided into normal weight and obese overweight groups according to their BMI status and WHtR classifications, which were low and high at < 0.50 and ≥ 0.50, respectively. Genotyping of BDNF rs6265 and rs7934165 polymorphisms was performed using a TaqMan assay. Distinct anthropometric, biochemical, clinical, and dietary parameters were obtained and used as covariates in the statistical analyses. The rs6265-G allele and its homozygote state (GG) were the most prominent without statistically significant differences between groups (p = 0.412). The study of rs7934165 with BMI showed marginal associations. Moreover, the rs7934165-AA genotype was more frequent among individuals with a high WHtR than those with a low WHtR (43.4 vs. 25.2%, p = 0.01). This association was maintained after adjustments for age and caloric intake through logistic regression analysis (OR = 2.20, 95% CI = 1.15-4.18, p = 0.016). The present study indicates that the BDNF-rs7934165-AA genotype is associated with a higher WHtR which is related to central obesity and its comorbidities. This suggests that this SNP could act as a potential biomarker for central obesity and cardiometabolic risk.

Sex-Based Differences in Cardiac Gene Expression and Function in BDNF Val66Met Mice.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic neuronal growth and survival factor that is indispensable in the brain, as well as in multiple other tissues and organs, including the cardiovascular system. In approximately 30% of the general population, BDNF harbors a nonsynonymous single nucleotide polymorphism that may be associated with cardiometabolic disorders, coronary artery disease, and Duchenne muscular dystrophy cardiomyopathy. We recently showed that transgenic mice with the human BDNF rs6265 polymorphism (Val66Met) exhibit altered cardiac function, and that cardiomyocytes isolated from these mice are also less contractile. To identify the underlying mechanisms involved, we compared cardiac function by echocardiography and performed deep sequencing of RNA extracted from whole hearts of all three genotypes (Val/Val, Val/Met, and Met/Met) of both male and female Val66Met mice. We found female-specific cardiac alterations in both heterozygous and homozygous carriers, including increased systolic (26.8%, p = 0.047) and diastolic diameters (14.9%, p = 0.022), increased systolic (57.9%, p = 0.039) and diastolic volumes (32.7%, p = 0.026), and increased stroke volume (25.9%, p = 0.033), with preserved ejection fraction and fractional shortening. Both males and females exhibited lower heart rates, but this change was more pronounced in female mice than in males. Consistent with phenotypic observations, the gene encoding SERCA2 (Atp2a2) was reduced in homozygous Met/Met mice but more profoundly in females compared to males. Enriched functions in females with the Met allele included cardiac hypertrophy in response to stress, with down-regulation of the gene encoding titin (Tcap) and upregulation of BNP (Nppb), in line with altered cardiac functional parameters. Homozygous male mice on the other hand exhibited an inflammatory profile characterized by interferon-γ (IFN-γ)-mediated Th1 immune responses. These results provide evidence for sex-based differences in how the BDNF polymorphism modifies cardiac physiology, including female-specific alterations of cardiac-specific transcripts and male-specific activation of inflammatory targets.

Lack of association between BDNF rs6265 polymorphism and risk of type 2 diabetes: A protocol for meta-analysis and trial sequential analysis.

Background:Brain-derived neurotrophic factor (BDNF) rs6265 polymorphism has been previously suggested to be associated with the susceptibility of type 2 diabetes mellitus (T2DM), but results remained controversial. We aim to provide a more reliable conclusion about the association between BDNF rs6265 polymorphism and T2DM risk by using a meta-analysis.Methods:Electronic databases such as Pubmed, Embase, CNKI, and Wanfang were searched for relevant articles published up to May 06, 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Subgroup analysis was carried out according to source of controls and quality score of included studies. A trial sequential analysis was conducted to reduce the risk of type I error.Results:A total of 8 case-control studies (7 conducted in China) with 1576 T2DM patients and 1866 controls were included. Overall, our results indicated no significant association between BDNF rs6265 polymorphism and T2DM risk with the random-effects model (allele model: pooled OR = 1.14, 95% CI = 0.79–1.65, homozygote model: pooled OR = 1.13, 95% CI = 0.57–2.21, heterozygote model: pooled OR = 1.07, 95% CI = 0.78–1.48, dominant model: pooled OR = 1.14, 95% CI = 0.74–1.75 and recessive model: pooled OR = 1.10, 95% CI = 0.67–1.80). Subgroup analysis by source of controls and quality score also showed no significant association between BDNF rs6265 polymorphism and T2DM risk. Trial sequential analysis results confirmed the null association and further studies were unnecessary.Conclusion:This meta-analysis study indicated that no significant association between BDNF rs6265 polymorphism and T2DM risk.

BDNF rs6265 Polymorphism and Its Methylation in Patients with Stroke Undergoing Rehabilitation.

Brain-Derived Neurotrophic Factor (BDNF) and its rs6265 single nucleotide polymorphism (SNP) play an important role in post-stroke recovery. We investigated the correlation between BDNF rs6265 SNP and recovery outcome, measured by the modified Barthel index, in 49 patients with stroke hospitalized in our rehabilitation center at baseline (T0) and after 30 sessions of rehabilitation treatment (T1); moreover, we analyzed the methylation level of the CpG site created or abolished into BDNF rs6265 SNP. In total, 11 patients (22.4%) were heterozygous GA, and 32 (65.3%) and 6 (12.2%) patients were homozygous GG and AA, respectively. The univariate analysis showed a significant relationship between the BDNF rs6265 SNP and the modified Barthel index cut-off (χ2(1, N = 48) = 3.86, p = 0.049), considering patients divided for carrying (A+) or not carrying (A−) the A allele. A higher percentage of A− patients obtained a favorable outcome, as showed by the logistic regression model corrected by age and time since the stroke onset, compared with the A+ patients (OR: 5.59). At baseline (T0), the percentage of BDNF methylation was significantly different between GG (44.6 ± 1.1%), GA (39.5 ± 2.8%) and AA (28.5 ± 1.7%) alleles (p < 0.001). After rehabilitation (T1), only patients A− showed a significant increase in methylation percentages (mean change = 1.3, CI: 0.4–2.2, p = 0.007). This preliminary study deserves more investigation to confirm if BDNF rs6265 SNP and its methylation could be used as a biological marker of recovery in patients with stroke undergoing rehabilitation treatment.

The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy.

Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, the effect of the Val66Met polymorphism on cardiac function has not been determined. The goal of the current study was to determine the effects of rs6265 on BDNF biomarker suitability and DMD cardiac functions more generally. We assessed cardiovascular and skeletal muscle function in human DMD patients segregated by polymorphic allele. We also compared echocardiographic, electrophysiologic, and cardiomyocyte contractility in C57/BL-6 wild-type mice with rs6265 polymorphism and in mdx/mTR (mDMD) mouse model of DMD. In human DMD patients, plasma BDNF levels had a positive correlation with left ventricular function, opposite to that seen in rs6265 carriers. There was also a substantial decrease in skeletal muscle function in carriers compared to the Val homozygotes. Surprisingly, the opposite was true when cardiac function of DMD carriers and non-carriers were compared. On the other hand, Val66Met wild-type mice had only subtle functional differences at baseline but significantly decreased cardiomyocyte contractility. Our results indicate that the Val66Met polymorphism alters myocyte contractility, conferring worse skeletal muscle function but better cardiac function in DMD patients. Moreover, these results suggest a mechanism for the relative preservation of cardiac tissues compared to skeletal muscle in DMD patients and underscores the complexity of BDNF signaling in response to mechanical workload.

Assessment of association of BDNF rs6265 polymorphism with apathy in Parkinson's Disease

Background: Apathy is a common behavioral problem in Parkinson's disease, with important clinical consequences for patients and their families. The neurobiology of this disorder is still unclear. The polymorphism of the brain-derived neurotrophic factor (BDNF) gene is associated with various neuropsychiatric diseases. Data from neuroimaging studies suggest an association between BDNF rs6265 (Val66Met) polymorphism and brain atrophy in regions, which have been linked to the pathogenesis of apathy.

Association between BDNF rs6265 polymorphisms and postoperative cognitive dysfunction in Chinese Han Population.

IntroductionBrain‐derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD). In present study, we aimed to assess the possible association between POCD and BDNF rs6265 polymorphisms.Methods124 patients aged 60 years or older scheduled for elective surgery under general anesthesia and 25 age‐ and gender‐matched healthy volunteers were recruited. POCD was identified using a neuropsychological test battery administered preoperatively, 7 days, and 3 months after surgery. Genotyping of rs6265 was performed using polymerase chain reaction amplification and restriction fragment length polymorphism analysis.Results99 patients and 25 healthy controls were finally enrolled in the analysis. 29(29.3%) and 18(18.2%) of 99 patients had POCD at 7 days and 3 months after surgery, respectively. The patients carrying a G allele at the rs6265 locus showed a lower risk for POCD than an A allele carriers on postoperative 7 days, but not 3 months after surgery (OR = 0.67; 95% CI: 0.47–0.96; p = .017; OR = 0.69; 95% CI: 0.42–1.13; p = .14, respectively). The risk of POCD at 7 days following surgery was significantly lower in additive model (OR = 0.41; 95% CI: 0.2–0.84; p = .015) and dominant model (OR = 0.35; 95% CI: 0.13–0.96; p = .042).ConclusionWe tentatively demonstrate that BDNF rs6265 polymorphisms might be associated with occurrence of POCD at 7 days after surgery and the A > G mutant at the rs6265 locus be likely a protective factor for early POCD in Chinese Han population.

Association of circulating BDNF levels with BDNF rs6265 polymorphism in schizophrenia

Schizophrenia is a severe neuropsychiatric disorder affecting 1% of the world population. Disturbances in neuronal development and synaptic connections are important factors in the pathogenesis of schizophrenia. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays a critical role in the development of neurons. Among several polymorphisms reported in BDNF, the rs6265 polymorphism is known to be associated with many neuropsychiatric diseases. This study was aimed to determine the effect of BDNF rs6265 functional polymorphism on serum BDNF concentration in patients with schizophrenia. In total, 50 schizophrenia patients and 50 controls were recruited after obtaining written informed consent. Serum BDNF levels were estimated using the ELISA method and BDNF rs6265 polymorphism was genotyped using T-ARMS PCR. Serum BDNF levels were decreased significantly in schizophrenia patients when compared to the healthy controls (p < 0.0001). Further, the rs6265 polymorphism was also not associated with the schizophrenia (p = 0.41). Intragroup analysis between different genotypes revealed no association between the serum BDNF levels and rs6265 polymorphism. Our results suggest that the functional polymorphism rs6265 is not associated with serum BDNF levels, which is in line with previous findings, which indicates that serum BDNF levels depend more on diagnostic effect than genetic effect. Replication studies on a larger study population are needed.

Negative association between left prefrontal GABA concentration and BDNF serum concentration in young adults

BackgroundThe brain's major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the brain-derived neurotrophic factor (BDNF) play important roles in several stress-related disorders. Magnetic resonance spectroscopy (MRS) allows for non-invasive quantification of GABA concentration in the brain. We investigated the relationship between GABA concentration in the left dorsolateral prefrontal cortex (DLPFC) and BDNF concentration in the serum in a community-based sample of young subjects. MethodsFor the GABA measurement a single voxel MR spectrum was assessed in the prefrontal lobe (25 × 40 × 30 mm) using the MEGA-PRESS method in 276 subjects. BDNF serum concentrations were assessed with an ELISA kit. For 147 subjects we had both MRS and BDNF serum data, and for 79 subjects we had genotype data on the BDNF rs6265 polymorphism. Depressive psychopathology was assessed using Beck's Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS) and Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders (SCID) for DSM-IV. ResultsGABA concentration in the left DLPFC was negatively associated with BDNF serum concentration (r = -.264, p = .001). This correlation remained significant if corrected for sex (r = -.264, p = .001). BDNF serum concentration was also positively associated with volumes and surface areas of the left prefrontal cortex (p = .048, p = .005). There were no significant associations or interaction with depressive psychopathology (BDI, MADRS, SCID) or rs6265. ConclusionThe results of this study suggest that GABA, BDNF and prefrontal brain volumes are interrelated, but do not show a strong association to depressive psychopathology, possibly due to the mild forms of psychiatric conditions present in our community-based sample.

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

Losing one’s only child is a major traumatic life event that may lead to posttraumatic stress disorder (PTSD); however, not all parents who experience this trauma develop PTSD. Genetic variants are associated with the risk of developing PTSD. Catechol-O-methyltransferase (COMT) rs4680 and brain-derived neurotrophic factor (BDNF) rs6265 are two most well-described single-nucleotide polymorphisms that relate to stress response; however, the neural mechanism underlying their effects on adults who lost an only child remains poorly understood. Two hundred and ten Han Chinese adults who had lost their only child (55 with PTSD and 155 without PTSD) were included in this imaging genetics study. Participants were divided into subgroups according to their COMT rs4680 and BDNF rs6265 genotypes. Degree Centrality (DC)—a resting-state fMRI index reflecting the brain network communication—was compared with a three-way (PTSD diagnosis, COMT, and BDNF polymorphisms) analysis of covariance. Diagnosis state had a significant effect on DC in bilateral inferior parietal lobules and right middle frontal gyrus (MFG), where PTSD adults showed weaker DC. BDNF × diagnosis interaction effect was found in the right MFG and hippocampus, and these two regions were reversely modulated. Also, there was a significant COMT × BDNF interaction effect in left cuneus, middle temporal gyrus, right inferior occipital gyrus, and bilateral putamen, independent of PTSD diagnosis. These findings suggest that the modulatory effect of BDNF polymorphism on the MFG and hippocampus may contribute to PTSD development in bereaved adults. Interactions of COMT × BDNF polymorphisms modulate some cortices and basal ganglia, irrespective of PTSD development.

The Distribution of Brain-Derived Neurotrophic Factor rs6265 Polymorphism in Turkish Volleyball Players

Athletic performance is associated with many environmental factors such as inborn genetic factors, nutrition, psychological factors, and education. We aimed to analyze the brain-derived neurotrophic factor (BDNF) rs6265 polymorphism, which is an important genetic marker related to psychological factors, in 21 professional female volleyball players and compare it with the control group. Genotyping was assessed by real-time polymerase chain reaction technique. BDNF rs6265 polymorphism genotypes were calculated as 72% and 28% for GG and GA in volleyball players, respectively. No AA genotype was detected. In the control group, the GG, GA, and AA genotype percentages were calculated as 57.8, 36.3, and 5.9, respectively. In the allelic distribution, the percentages in the athlete group were calculated as 86% (36) for the G allele and 14% (6) for the A allele, respectively. In the control group, for the G and A alleles, respectively, it was 76.25% and 23.75%. No statistical significance was found in terms of both genotype distribution (P = 0.407) and allelic frequency distribution (P = 0.218). Our results were in line with data indicating the stress and anxiety-related nature of professional volleyball players. More studies with more athletes and more groups of athletes are needed to understand the effect of these parameters on volleyball players.