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The Influence of Val66Met Polymorphism in Brain-Derived Neurotrophic Factor on Stroke Recovery Outcome: A Systematic Review and Meta-analysis.
Liu, X, Fang, JC, Zhi, XY, Yan, QY, Zhu, H, Xie, J
Neurorehabilitation and neural repair. 2021;(6):550-560
Abstract
Background and purpose. A single nucleotide polymorphism at nucleotide 196 (G/A) in the human brain-derived neurotrophic factor (BDNF) gene produces an amino acid substitution (valine to methionine) at codon 66(Val66Met). It is unclear whether carriers of this substitution may have worse functional outcomes after stroke. We aimed to explore the distribution of Val66Met polymorphism and evaluate the effect of different genotypes on stroke functional recovery. Methods. Several databases were searched using the keywords BDNF or brain-derived neurotrophic factor, codon66, G196A, rs6265, or Val66Met, and stroke. Results. A total of 25 articles were relevant to estimate the distribution of alleles; 5 reports were applied in the meta-analysis to assess genetic differences on recovery outcomes. The genetic model analysis showed that the recessive model should be used; we combined data for AA versus GA+GG (GG-Val/Val, GA-Val/Met, AA-Met/Met). The results showed that stroke patients with AA might have worse recovery outcomes than those with GA+GG (odds ratio = 1.90; 95% CI: 1.17-3.10; P = .010; I2 = 69.2%). Overall, the A allele may be more common in Asian patients (48.6%; 95% CI: 45.8%-51.4%, I2 = 54.2%) than Caucasian patients (29.8%; 95% CI: 7.5%-52.1%; I2 = 99.1%). However, in Caucasian patients, the frequency of the A allele in Iranians (87.9%; 95% CI: 83.4%-92.3%) was quite higher than that in other Caucasians (18.7%; 95% CI: 16.6%-20.9%; I2 = 0.00%). Conclusion. Val66Met AA carriers may have worse rehabilitation outcomes than GA+GG carriers. Further studies are needed to determine the effect of Val66Met polymorphism on stroke recovery and to evaluate this relationship with ethnicity, sex, age, stroke type, observe duration, stroke severity, injury location, and therapies.
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The role of physical exercise in modulating peripheral inflammatory and neurotrophic biomarkers in older adults: A systematic review and meta-analysis.
Titus, J, Bray, NW, Kamkar, N, Camicioli, R, Nagamatsu, LS, Speechley, M, Montero-Odasso, M
Mechanisms of ageing and development. 2021;:111431
Abstract
BACKGROUND Physiological cascades of neurotrophic factors and inflammatory cytokines may mediate the exercise-induced amelioration of cognition in older adults. However, there is limited understanding on how different exercise modalities improving cognition alter biomarkers. Our aim was to evaluate the effects of different exercise modalities on blood biomarker concentrations in cognitive clinical trials of older adults. METHODS A systematic review (SR) and meta-analysis (MA) were performed using the databases PubMed, EMBASE, and SCOPUS. After exclusions, 17 trials with 18 distinct exercise interventions were included. RESULTS Aerobic training increased (n = 2) or did not significantly change BDNF (n = 5), and resistance training increased (n = 2) or did not significantly change (n = 2) IGF-1. Multimodal training significantly increased (n = 1) or did not change (n = 3) BDNF. Interventions that recruited sex-specific cohorts showed an advantage in males for blood marker concentrations and cognitive performance outcomes (n = 3) compared to females (n = 3). Only one of three interventions decreased concentrations of CRP. Eight studies examining BDNF changes were suited for MA and showed that higher BDNF concentrations were reached post intervention, although not reaching statistical significance (p = .26, I2 = 44 %). DISCUSSION Our results suggest that exercise has potential to ameliorate cognitive decline in older adults with divergent, modality-specific, neurotrophic mechanisms.
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Meta-analytic method reveal a significant association of theBDNF Val66Met variant with smoking persistence based on a large samples.
Zhao, H, Xiong, S, Li, Z, Wu, X, Li, L
The pharmacogenomics journal. 2020;(3):398-407
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Abstract
Although numerous genetic studies have reported the link between Val66Met in BDNF gene with smoking, the findings remain controversial, mainly due to small-to-moderate sample sizes. The main aim of current investigation is to explore whether the variant of Val66Met has any genetic functions in the progress of smoking persistence. The Val-based dominant genetic model considering Val/* (namely, Val/Val + Val/Met) and Met/Met as two genotypes with comparison of the frequency of each genotype in current smokers and never smokers. There were seven genetic association articles including eight independent datasets with 10,160 participants were chosen in current meta-analytic investigation. In light of the potent effects of ethnicity on homogeneity across studies, we carried out separated meta-analyses according to the ancestry origin by using the wide-used tool of Comprehensive Meta-analysis software (V 2.0). Our meta-analyses results indicated that the Val66Met polymorphism was significantly linked with smoking persistence based on either all the chosen samples (N = 10,160; Random and fixed models: pooled OR = 1.23; 95% CI = 1.03-1.46; P value = 0.012) or Asian samples (N = 2,095; Fixed model: pooled OR = 1.25; 95% CI = 1.01-1.54; P value = 0.044; Random model: pooled OR = 1.25; 95% CI = 1.001-1.56; P value = 0.049). No significant clue of bias in publications or heterogeneity across studies was detected. Thus, we conclude that the Val66Met (rs6265) variant conveys genetic susceptibility to maintaining smoking, and smokers who carry Val/* genotypes have a higher possibility of maintaining smoking than those having Met/Met genotype.
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Association of Brain-derived neurotrophic factor gene polymorphisms with body mass index: A systematic review and meta-analysis.
Akbarian, SA, Salehi-Abargouei, A, Pourmasoumi, M, Kelishadi, R, Nikpour, P, Heidari-Beni, M
Advances in medical sciences. 2018;(1):43-56
Abstract
BACKGROUND Many studies with inconsistent results have assessed the association of Brain-derived neurotrophic factor (BDNF) gene polymorphisms with prevalence of obesity and overweight. This review aims to provide a summary of the literature evaluating the relation between BDNF genotype and body mass index (BMI). METHODS A systematic search through PubMed, Scopus, Science direct, Ovid and Cochrane was performed. We included observational studies with cross-sectional and case-control design, which investigated relationship between all kinds of BDNF polymorphisms with BMI, as a representative index of obesity and overweight. Newcastle-Ottawa Scale was used to assess the quality of included articles. RESULTS Thirty five studies were included in quantitative synthesis. Analyses were performed separately using OR, β coefficient and mean. Significant association were documented between rs925946 and BMI (OR=1.12, 95% CI=1.08-1.17, P heterogeneity=0.317), rs10501087 and BMI (OR=1.14, 95% CI=1.04-1.24, P heterogeneity=0.861), rs6265 and BMI (OR=1.13, 95% CI=1.07-1.19, P heterogeneity=0.406), rs988712 and BMI (OR=1.29, 95% CI=1.18-1.40, P heterogeneity=0.602). According to pooled β coefficient analysis, significant result was only observed in the rs925946 polymorphism subgroup. Pooled mean analysis showed that overall effects for the association between BDNF polymorphisms and BMI were not statistically significant. CONCLUSION This meta-analysis suggests that some polymorphisms in BDNF gene including rs925946, rs10501087, rs6265 and rs988712 can be considered as genetic determinants of obesity.
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The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis.
Sanada, K, Zorrilla, I, Iwata, Y, Bermúdez-Ampudia, C, Graff-Guerrero, A, Martínez-Cengotitabengoa, M, González-Pinto, A
International journal of molecular sciences. 2016;(10)
Abstract
Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs) between the intervention groups and controls. In total, six randomized controlled trials with 289 participants were included. Of them, five studies used exercise, physical training or diet products. One study used cognitive training. Overall, the BDNF levels in the NPI group increased significantly compared with the control groups (SMD = 0.95, 95% confidence interval (CI) = 0.07 to 1.83, p = 0.03). Subgroup analyses indicated beneficial effects of a non-exercise intervention on peripheral BDNF levels (SMD = 0.41, 95% CI = 0.08 to 0.74, p = 0.01). Meta-regression analyses showed that the completion rate influenced the variation in SMD (p = 0.01). Despite insufficient evidence to draw a conclusion, our results suggest that use of NPIs as adjunctive treatments, specifically non-exercise interventions, may affect positively serum or plasma BDNF in patients with schizophrenia.
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BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis.
Harrisberger, F, Smieskova, R, Schmidt, A, Lenz, C, Walter, A, Wittfeld, K, Grabe, HJ, Lang, UE, Fusar-Poli, P, Borgwardt, S
Neuroscience and biobehavioral reviews. 2015;:107-18
Abstract
BACKGROUND Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity in the central nervous system, especially in the hippocampus, and has been implicated in the pathophysiology of several neuropsychiatric disorders. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a functionally relevant single nucleotide polymorphism affecting the secretion of BDNF and is implicated in differences in hippocampal volumes. METHODS This is a systematic meta-analytical review of findings from imaging genetic studies on the impact of the rs6265 SNP on hippocampal volumes in neuropsychiatric patients with major depressive disorder, anxiety, bipolar disorder or schizophrenia. RESULTS The overall sample size of 18 independent clinical cohorts comprised 1695 patients. Our results indicated no significant association of left (Hedge's g=0.08, p=0.12), right (g=0.07, p=0.22) or bilateral (g=0.07, p=0.16) hippocampal volumes with BDNF rs6265 in neuropsychiatric patients. There was no evidence for a publication bias or any demographic, clinical, or methodological moderating effects. Both Val/Val homozygotes (g=0.32, p=0.004) and Met-carriers (g=0.20, p=0.004) from the patient sample had significantly smaller hippocampal volumes than the healthy control sample with the same allele. The magnitude of these effects did not differ between the two genotypes. CONCLUSION This meta-analysis suggests that there is no association between this BDNF polymorphism and hippocampal volumes. For each BDNF genotype, the hippocampal volumes were significantly lower in neuropsychiatric patients than in healthy controls.
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Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications.
Fernandes, BS, Steiner, J, Berk, M, Molendijk, ML, Gonzalez-Pinto, A, Turck, CW, Nardin, P, Gonçalves, CA
Molecular psychiatry. 2015;(9):1108-19
Abstract
It has been postulated that schizophrenia (SZ) is related to a lower expression of brain-derived neurotrophic factor (BDNF). In the past few years, an increasing number of divergent clinical studies assessing BDNF in serum and plasma have been published. It is now possible to verify the relationship between BDNF levels and severity of symptoms in SZ as well as the effects of antipsychotic drugs on BDNF using meta-analysis. The aims of this study were to verify if peripheral BDNF is decreased in SZ, whether its levels are correlated with positive and negative symptomatology and if BDNF levels change after antipsychotic treatment. This report consists of two distinct meta-analyses of peripheral BDNF in SZ including a total of 41 studies and more than 7000 participants: (1) peripheral BDNF levels in serum and plasma were moderately reduced in SZ compared with controls. Notably, this decrease was accentuated with the disease duration. However, the extent of peripheral BDNF level decrease did not correlate with the severity of positive and negative symptoms. (2) In plasma, but not serum, peripheral BDNF levels are consistently increased after antipsychotic treatment irrespective of the patient's response to medication. In conclusion, there is compelling evidence that there are decreased levels of peripheral BDNF in SZ, in parallel to previously described reduced cerebral BDNF expression. It remains unclear whether these systemic changes are causally related to the development of SZ or if they are merely a pathologic epiphenomenon.
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Does BDNF Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder?
Wang, T
Neuropsychobiology. 2015;(3):149-53
Abstract
BACKGROUND Evidence has indicated that BDNF (brain-derived neurotrophic factor) Val66Met genetic variant could be linked to the development of posttraumatic stress disorder (PTSD). However, clinical observations studying the BDNF polymorphism and the risk of PTSD yielded contradictory results. In this meta-analysis we evaluated the association between BDNF Val66Met and PTSD risk. METHOD Systematic searches in online databases retrieved 6 relevant publications. Different inherited models were utilized to perform the pooled analysis. Subgroup analyses and sensitive analyses based on Hardy-Weinberg equilibrium (HWE) test results were also carried out. RESULTS Our study did not found a significant overall effect of BDNF Val66Met on the susceptibility to PTSD under various genetic models. In contrast, subgroup analyses suggested that the stress status of the control group, but not ethnicity, may influence the relationship of BDNF Val66Met with PTSD risk. After the exclusion of a study that was not in HWE, our conclusions remained unchanged during the influence analyses. CONCLUSIONS This meta-analysis suggested no genetic association of BDNF Val66Met with vulnerability to PTSD. Further research studies are warranted to clarify the impact of BDNF variants on the occurrence of PTSD.
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Meta-analysis study on the role of bone-derived neurotrophic factor Val66Met polymorphism in Parkinson's disease.
Mariani, S, Ventriglia, M, Simonelli, I, Bucossi, S, Siotto, M, R, RS
Rejuvenation research. 2015;(1):40-7
Abstract
To evaluate a possible involvement of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in susceptibility to Parkinson's disease (PD), we performed a meta-analysis of all studies on the topic published from 2002 to 2014. This article reviews and compares the data from two previous meta-analyses, including two studies not previously considered. We selected studies referring to a genetic comparison between PD patients and healthy controls, so 15 studies involving 3754 cases and 4026 controls were included in our meta-analysis. We found no association between the Val66Met polymorphism and the risk of developing PD in our overall analysis. The ethnicity-specific meta-analysis produced no significant association either. Our data do not support a major role for the BDNF Val66Met polymorphism in the pathogenesis of PD.
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BDNF Val66Met polymorphism and antipsychotic-induced tardive dyskinesia occurrence and severity: a meta-analysis.
Miura, I, Zhang, JP, Nitta, M, Lencz, T, Kane, JM, Malhotra, AK, Yabe, H, Correll, CU
Schizophrenia research. 2014;(2-3):365-72
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Abstract
BACKGROUND Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. METHODS Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges' g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. RESULTS Out of 699 potentially eligible hits, 6 studies (N=1740, mean age=46.0±10.4years; males=73.1%; Asians=80.5%, Caucasians=19.5%; schizophrenia=96.2%) were included in this meta-analysis. Pooling data from all studies, no significant associations were found between BDNF Val66Met polymorphism and TD (p=0.82) or AIMS total scores (p=0.11). However, in studies including only Caucasians (n=339), Met allele carriers had significantly higher AIMS total scores (Hedges' g=0.253, 95% confidence interval=0.030 to 0.476, p=0.026) and non-significantly higher TD occurrence (p=0.127). Conversely, there was no association between BDNF and AIMS scores (p=0.57) or TD (p=0.65) in Asians. CONCLUSION Although there was no significant association between BDNF Val66Met polymorphism and TD or AIMS scores across all patients, our results suggest that BDNF Val66Met polymorphism affects severity and, possibly, TD development in Caucasians. Since the number of studies and patients was still small, additional data are needed to confirm genotype-racial interactions. Furthermore, BDNF enhancing treatments for TD may require further study, especially in Caucasians.