Association Of Brain-derived Neurotrophic Factor Research Articles

Associations Between ApoEε4 Carrier Status and Serum BDNF Levels--New Insights into the Molecular Mechanism of ApoEε4 Actions in Alzheimer's Disease.

Insufficient neurotrophic support increases the risk for developing Alzheimer's disease (AD). Mounting evidence has confirmed the association of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) with AD. As both BDNF and ApoE are suggested to be involved in modulating brain integrity, the present study is aiming to investigate the associations between these two factors. In this study, 110 AD patients and 120 cognitively normal controls (NC) were recruited for measurement of serum BDNF levels and ApoE genotyping. Serum BDNF levels in the AD group were significantly lower than that in the NC group, reflecting insufficient neurotrophic supply in AD patients. We further found that ApoE ε4+/- and ε4+/+ subjects had significantly lower serum BDNF levels than ε4-/- subjects in the whole cohort and the NC group, suggesting altered BDNF metabolism in ApoE ε4 carriers. Further analysis indicated possible interactions between ApoEε4 and BDNF in their co-effects on AD and mini-mental state examination (MMSE) scores. Our findings imply that the possible involvement of ApoE ε4 in BDNF metabolism might be another molecular mechanism underlying the contribution of ApoE ε4 to the development of AD.

Sex-specific association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and plasma BDNF with attention-deficit/hyperactivity disorder in a drug-naïve Han Chinese sample

A functional polymorphism of the brain derived neurotrophic factor gene (BDNF) (Val66Met) has been suggested to be involved in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). It also has an impact on peripheral BDNF levels in psychiatric disorders. This study examined the association of Val66Met with plasma BDNF level of ADHD in Han Chinese children (170 medication – naïve ADHD patients and 155 unaffected controls, aged 6–16 years). The Val allele was showed a higher frequency in females with ADHD (n=84) than controls (P=0.029) from the case-control association study. The analysis of covariance (ANCOVA) indicated that the mean plasma BDNF levels of ADHD patients were significantly higher than that of controls (P=0.001). We performed both total sample and sex stratified analyses to investigate the effect of Val66Met genotype on the plasma BDNF levels, but only a trend of association was found in females with ADHD (n=84), with a tendency of lower plasma BDNF level in Val allele carriers than Met/Met genotype carriers (P=0.071). Our results suggested a sex-specific association between BDNF and ADHD. Furthermore, there was a possible sex-specific relationship between the BDNF Val66Met genotype and plasma BDNF levels. However, further studies are required to elucidate the role of BDNF in ADHD.

Brain-derived Neurotrophic Factor Genetic Variants are Associated with Major Depression Susceptibility and Serotonin Reuptake Inhibitor Antidepressant Treatment Response in Taiwanese

The involvement of neurotrophic factors, notably brain-derived neurotrophic factor (BDNF) has been suggested in the pathogenesis of major depressive disorder (MDD) and in the response of antidepressant treatment both in preclinical and clinical studies. Thus, genetic variation in human BDNF gene may be associated with MDD susceptibility and be related to treatment response to antidepressants in patients with MDD. Two hundred and eighty-eight Taiwanese patients diagnosed with MDD and 397 participants with similar mean age and gender distribution were enrolled in the study, and three markers, including rs6265 (Val66Met) in the BDNF gene were examined for their association with MDD and 4-week response to selective serotonin reuptake inhibitors (SSRI) (n = 216) using single- and haplotype-based analyses. The results showed that the Met allele of rs6265 was in allelic association with MDD. Haplotype analysis of marker combination rs2049046-rs7103411-rs6265 further indicated the association between BDNF genetic polymorphisms and MDD (global permutation p = 0.0007). Regarding 4-week SSRI treatment response and controlling the effect of relevant covariates using logistic regression, the heterozygotes of rs7103411 and rs6265 had higher treatment responder percentage than their homozygous analogs. Furthermore, MDD patients carrying AGA-TAG diplotype tended to be the responders to 4-week SSRIs treatment compared with the non-AGA-TAG diplotype carriers (corrected p= 0.048). One strength of our study is the relatively large sample size. Our findings suggest that BDNF may be a susceptibility gene for MDD, and may also confer a heterosis effect for antidepressant treatment response. Keywords: Brain-derived neurotrophic factor association, depression, heterosis effect, polymorphism, selective serotonin reuptake inhibitor.

Association of brain-derived neurotrophic factor and tyrosine kinase B receptor in pregnancy

Abnormal brain development in a compromised prenatal and/or early postnatal environment is thought to be a risk factor for several neurobehavioural disorders. However, the mechanisms underlying these are not well understood. We have earlier reported reduced placental docosahexaenoic acid (DHA) levels in preterm deliveries. We have hypothesized that increased oxidative stress and reduced DHA levels may lead to changes in the circulating levels of maternal and cord brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) levels. A total number of 96 women delivering preterm and 95 women delivering at term were recruited. Plasma BDNF levels were measured in both mother and cord blood plasma using the BDNF Immuno Assay kit. Placental TrkB levels were analysed using sandwich enzyme-linked immunosorbent assay (ELISA). Maternal plasma BDNF levels and placental TrkB levels were higher (p<0.05) while cord plasma BDNF levels were lower (p<0.01) in women delivering preterm as compared to term. There was a negative association between levels of placental TrkB and DHA (p=0.034). A negative association between maternal plasma BDNF levels and placental weight (p=0.001) was observed while a positive association was seen between cord plasma BDNF levels and gestation (p=0.025). The reduction in cord BDNF levels may have implications for altered neurodevelopment in childhood and later life. Studies need to be undertaken to follow up children born preterm for risk of neurobehavioural disorders like attention deficit hyperactivity disorder (ADHD) to understand the effect of altered BDNF at birth on neurodevelopment.

Association of brain-derived neurotrophic factor ( BDNF) Val66Met polymorphism with Parkinson’s disease in a Greek population

Brain-derived neurotrophic factor (BDNF) enhances survival of dopaminergic neurons in the substantia nigra, whereas in patients with Parkinson’s disease (PD), the expression of BDNF mRNA is decreased, thus making BDNF a candidate gene for PD susceptibility. The association between BDNF Val66Met polymorphism and PD has been evaluated in several studies with controversial results. Thus, we determined the distribution of BDNF Val66Met polymorphism in 184 Greek patients with sporadic PD and 113 control participants using polymerase chain reaction–restriction fragment length polymorphism, and explored the association of the polymorphism with certain clinical parameters of the disease. Our results do not support a major role for the BDNF Val66Met polymorphism in PD in the Greek population.

Association of brain-derived neurotrophic factor (Val66Met) genetic polymorphism with methamphetamine dependence in a Malaysian population

Methamphetamine is a highly addictive psychostimulant that has surged in popularity worldwide in the last decade. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is widely expressed in the adult mammalian brain and plays an important role in the long-term survival, differentiation, and outgrowth of neurons. Previous studies suggested that the BDNF gene may be involved in the mechanisms underlying substance dependence. This study investigated the association of the BDNF gene Val66Met polymorphism with methamphetamine dependence and with psychosis in a Malaysian population with different ethnicities. The BDNF Val66Met polymorphism was genotyped by PCR-RFLP in 186 male methamphetamine-dependent subjects and in 154 male controls of four different ethnicities, namely, Malay, Chinese, Kadazan-Dusun, and Bajau. Our results showed that the distribution of the BDNF Val66Met genotype in Chinese subjects with methamphetamine dependence (OR = 2.6, p = 0.015) and methamphetamine psychosis (OR = 0.2, p = 0.034) were significant compared with controls. The frequency of the 66Val allele in methamphetamine-dependent subjects was higher than that in the control group, suggesting that the 66Val carriers are more susceptible to methamphetamine dependence. However, 66Val allele frequency in other ethnicities was not significantly different from the controls. The results of the study also showed that in the Chinese methamphetamine-dependent subjects, there was a difference in allele frequency when comparing those who developed psychosis and those who did not. Our findings suggest that the BDNF Val66Met polymorphism may contribute to methamphetamine dependence and psychosis in the Chinese population but not in other Malaysian ethnicities.

Association Of Brain-derived Neurotrophic Factor With Physical Activity And Cardiovascular Disease Risk Factors

Brain-derived neurotrophic factor (BDNF) is an important molecular mediator of structural and functional plasticity in the brain. It is now acceptable that regular physical activity increases BDNF level in various brain regions and it has been believed that serum-BDNF levels could be used to indirectly assess brain-BDNF levels. However, recent studies provided possibilities that circulating BDNF may not reflect brain-BDNF and that it may be associated with cardiovascular disease risk factors (CDRF). PURPOSE: To examine the association of serum BDNF with maximal oxygen consumption (VO2max/kg), moderate physical activity (MPAT) and CDRFs. METHODS: Healthy young adult (age range: 21-29 years, n=88) and middle-aged adult (41-55 years, n=447) men were participated as a part of the Preventive Health Study, Sports Science Institute, Yong-in Univ., Korea. When coming to laboratory after an overnight fast, participants were asked to take a 30-min rest followed by venous blood sampling. After the blood sampling, VO2max/kg was assessed by a maximal treadmill test. Serum-BDNF was analyzed by ELISA kits (Bio-Rad, USA), while total cholesterol (TC), triglyceride (TG) and low- and high-density lipoprotein cholesterol (LDL and HDL) were measured by UV methods (Hitachi U-2800, Japan). MPAT was measured by using international physical activity questionnaire. Pearson product moment correlation was conducted to analyze an association of serum BDNF to MPAT and VO2max/kg within each group. RESULTS: Our study resulted in a significantly inverse relationship between serum BDNF and MPAT (r=-0.79 and r=-0.78) and VO2max/kg (r=-0.42 and r=-0.33) in young and middle-aged adult groups respectively (P<0.0001). Our results showed a significant, linear correlation between serum BDNF and BMI (r=0.80 and r=0.81), SBP (r=0.33 and r=0.24) and triglyceride level (r=0.31 and r=0.35) in young and middle-aged adult groups respectively (P<0.0001). CONCLUSION: In conclusion, our data show that serum BNDF is associated with increases in cardiovascular disease risk factors and inversely associated with levels of physical activity within each aged group. However, because of the cross-sectional nature of the study, a future research is warranted to elucidate the possible mechanisms for these relationships for circulatory BDNF.

Brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T are not associated with response to electroconvulsive therapy in major depressive disorder

The aim of the present study was to examine an association of brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study group consisted of 119 patients consecutively admitted for ECT in the Department of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic criteria of DSM-IV for MDD. ECT was administered three times a week with a brief pulse constant current device. The Montgomery and Asberg Depression Rating Scale (MADRS) was used as an outcome measure of depression. Genotyping was performed using fluorescent allele-specific TaqMan probes. No association between either G196A or C270T and the response to ECT was found in the whole population. There were no significant differences in responses between men and women or between psychotic and non-psychotic patients. However, within subgroups such as in psychotic and in late-onset depression CC genotype of C270T may predict good response. BDNF may not be associated with response to ECT in general, but some association in subgroups may exist.