Correlations of Four Genetic Single Nucleotide Polymorphisms in Brain-Derived Neurotrophic Factor with Posttraumatic Stress Disorder.
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ABSTRACT:
SUBMITTER: Guo JC
PROVIDER: S-EPMC5912493 | biostudies-literature | 2018 Apr
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Brain-derived neurotrophic factor (BDNF) is a neurotrophin found in abundance in brain regions such as the hippocampus, cortex, cerebellum and basal forebrain. It has been associated with the risk of susceptibility to major depressive disorder (MDD). This study aimed to determine the association of three BDNF variants (rs6265, rs1048218 and rs1048220) with Malaysian MDD patients. METHODS:The correlation of these variants to the plasma BDNF level among Malaysian MDD patients was assessed. A total of 300 cases and 300 matched controls recruited from four public hospitals within the Klang Valley of Selangor State, Malaysia and matched for age, sex and ethnicity were screened for BDNF rs6265, rs1048218 and rs1048220 using high resolution melting (HRM). FINDINGS:BDNF rs1048218 and BDNF rs1048220 were monomorphic and were excluded from further analysis. The distribution of the alleles and genotypes for BDNF rs6265 was in Hardy-Weinberg equilibrium for the controls (p = 0.13) but was in Hardy Weinberg disequilibrium for the cases (p = 0.011). Findings from this study indicated that having BDNF rs6265 in the Malaysian population increase the odds of developing MDD by 2.05 folds (95% CI = 1.48-3.65). Plasma from 206 cases and 206 controls were randomly selected to measure the BDNF level using enzyme-linked immunosorbent assay (ELISA). A significant decrease in the plasma BDNF level of the cases as compared to controls (p<0.0001) was observed. However, there was no evidence of the effect of the rs6265 genotypes on the BDNF level indicating a possible role of other factors in modulating the BDNF level that warrants further investigation. CONCLUSION:The study indicated that having the BDNF rs6265 allele (A) increase the risk of developing MDD in the Malaysian population suggesting a possible role of BDNF in the etiology of the disorder.
| S-EPMC6345459 | biostudies-literature
Project description:Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial. The other frequently studied BDNF polymorphism, C270T (rs56164415), has been associated with the development of different neuropsychiatric symptoms/disorders. As far as we are aware, there are no data on the association of BDNF Val66Met and C270T polymorphisms with metabolic indices in PTSD. Due to high rates of obesity and dyslipidaemia in PTSD, the aim of this study was to elucidate the association of BDNF Val66Met and C270T polymorphisms with BMI and lipid levels in veterans with PTSD. We hypothesized that BDNF variants contribute to susceptibility to metabolic disturbances in PTSD. The study included 333 Caucasian males with combat related PTSD, diagnosed according to DSM-5 criteria. Genotyping of the BDNF Val66Met and C270T polymorphisms was performed using the real-time PCR method. Results were analyzed using hierarchical multiple linear regression and the Mann-Whitney test, with p-value corrected to 0.005. The results showed that BDNF Val66Met and BDNF C270T polymorphisms were not significantly associated with BMI, total cholesterol, LDL-cholesterol, HDL-cholesterol or triglycerides. Although the BDNF C270T polymorphism was nominally associated only with HDL-cholesterol in veterans with PTSD, this significance disappeared after controlling for the effect of age. Namely, slightly higher plasma HDL values in T allele carriers, compared to CC homozygotes, were associated with differences in age. Our results, controlled for the critical covariates, revealed that BDNF Val66Met and C270T were not significantly associated with metabolic indices in veterans with PTSD and that these genetic variants do not contribute to susceptibility to metabolic disturbances in PTSD.
| S-EPMC6277864 | biostudies-literature
Project description:Genetic variation at the locus encoding the brain derived neurotrophic factor (BDNF) has been implicated in some neuropsychiatric disorders such as Alzheimer's disease (AD), affective disorders (AFDs), schizophrenia, and substance dependence. We therefore performed a mutation scan of the BDNF gene to identify novel gene variants and examined the association between BDNF variants and several neuropsychiatric phenotypes in European American (EA) subjects and controls. Using denaturing high performance liquid chromatography (dHPLC), we identified a novel variant (G-712A) in the putative promoter region. This variant and two previously reported BDNF SNPs (C270T and Val66Met) were genotyped in 295 patients with AD, 108 with AFDs, 96 with posttraumatic stress disorder (PTSD), 84 with schizophrenia, 327 with alcohol and/or drug dependence, and 250 normal control subjects. No association was found between these three BDNF gene variants and AD, AFDs, PTSD, or schizophrenia. However, there was a nominally higher frequency of the G-712A G-allele and the G/G genotype in subjects with substance dependence than in controls (Allele: chi(2) = 4.080, df = 1, P = 0.043; Genotype: chi(2) = 7.225, df = 2, P = 0.027). Although after correction for multiple testing, the findings are not considered significant (threshold P-value was set at 0.020 by the program SNPSpD), logistic regression analyses confirmed the modest association between SNP G-712A and substance dependence, when the sex and age of subjects were taken into consideration. The negative results for AFDs, PTSD, and schizophrenia could be due to the low statistical power. Further study with larger samples is warranted.
| S-EPMC2567822 | biostudies-literature
Project description:BackgroundAutism Spectrum Disorder (ASD) is a complex neurobehavioral syndrome with no known biomarker so far for early detection. It has been challenging, both to classify typical autism and associate a suitable biomarker with clinical phenotype spectrum. Brain-derived neurotrophic factor (BDNF) has emerged as a key neurotrophin regulating synaptic plasticity, neuronal differentiation and survival.PurposeRecently, BDNF depletion is reported in neurodegenerative as well as in psychiatric disorders, associated with severity of neurological dysfunction. Role of BDNF as a biomarker in ASD is gaining significance. Pre-clinical results have linked BDNF depletion in autism and mental retardation, however, with conflicting findings.MethodsIn view of this, a preliminary study was carried out to measure serum BDNF levels in 48 children with ASD and mental retardation, and 29 age-matched controls.ResultsSerum BDNF levels were found significantly higher (p<0.001) in atypical autistic subjects (clinically milder phenotype) as compared to controls, but not in typical ASD cases (clinically severe phenotype). BDNF levels were significantly lower in females with typical/Rett Syndrome (p<0.05), but not in males with typical autism (p>0.1), as compared to controls. Lower BDNF levels indicate impairment in neuroprotective mechanism, while higher levels may imply a manifested protective response.ConclusionOur study highlights the differential BDNF response based on the severity of neurobehavioral deficit, indicating a possible neuroprotective role of this molecule and supporting its exploration in targeted therapy in ASD.
| S-EPMC4248479 | biostudies-literature
Project description:In this study of the effect of bipolar status and presence of BDNF Val66Met polymorphism on differences in regional brain volumes, we hypothesized based on previous studies that 1) bipolar subjects will have smaller regional brain volumes than healthy controls; 2) BDNF Met66 allele carriers within the same population are likely to have smaller regional brain volumes as compared to Val66 homozygyotes. In our Caucasian sample of 166 bipolar subjects and 64 gender-matched healthy controls, we found significant decreases in total (p = 0.005) and regional gray matter volumes in bipolar patients compared to healthy controls, more pronounced in the inferior and posterior parts of the brain, together with a concomitant increase in total CSF (p = 0.012) particularly in the lateral ventricles (p = 0.023). However, there was no difference in white matter volumes noted by other studies. Furthermore we did not find significant differences in other brain regions that have been reported by other authors. Nor did we find a significant effect of BDNF on these measurements.
| S-EPMC3408450 | biostudies-literature
Project description:ObjectiveSeveral lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a role in the pathophysiology of anxiety. We analyzed the association of the BDNF gene polymorphism, G196A (val66met), in the coding region of exon XIIIA in chromosome 11p13, and generalized social anxiety disorder (GSAD).MethodsPatients with GSAD (n=73) and age-matched control subjects (n=152) were tested for the BDNF (val66met) polymorphism. A clinical interview and a Mini-International Neuropsychiatric Interview were conducted by trained psychiatrists in order to diagnose GSAD. The symptomatic characteristics of the GSAD patients were assessed with the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Retrospective Self Report of Inhibition, the Spielberger State-Trait Anxiety Inventory, and the Liebowitz Social Anxiety Scale.ResultsThere were no significant differences in the frequencies of the genotypes (χ(2)=0.961, degree of freedom [df]=2, p=0.619), alleles (χ(2)=0.415, df=1, p=0.519), or allele (methionine) carriers (χ(2)=0.019, df=1, p=0.889) between the patients and controls. In addition, when we compared the severity of social anxiety symptom as determined by the clinical scales with the genotypes of the BDNF gene, we could not find any significant differences between the genotypes or allele carriers.ConclusionThese results do not support the hypothesis that the BDNF gene might be a candidate gene for susceptibility or severity of GSAD in the Korean population in this study.
| S-EPMC3569117 | biostudies-literature
Project description:Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of major depressive disorder (MDD). In this mini review, we explored the association between BDNF and MDD using meta-analytic evidence. Our findings indicated that the Val66Met polymorphism in the BDNF gene was not associated with MDD or hippocampal volume in patients with MDD. However, plasma/serum levels of BDNF were decreased in patients with acute MDD compared with healthy controls. Both antidepressant treatment and electroconvulsive therapy increased plasma and serum levels of BDNF in patients with MDD. Val66Met polymorphism in the BDNF gene was associated with an antidepressant response in patients with MDD. Taken together, we did not detect any plausible evidence regarding Val66Met polymorphism in the BDNF gene contributing to a risk of MDD. However, peripheral BDNF levels are decreased in patients with MDD, and the polymorphisms are associated with treatment response. In conclusion, BDNF is best understood to be a biomarker for the state of MDD and its treatment response rather than a risk factor for MDD.
| S-EPMC5776079 | biostudies-literature
Project description:ObjectiveBrain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders.MethodsTen single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families. Family-based association analysis was used with three hierarchical bipolar disorder models to test for an association between SNPs in BDNF and the risk of bipolar disorder. In addition, an exploratory analysis was performed to test for an association of the SNPs in BDNF and the phenotypes of rapid cycling and episode frequency.ResultsEvidence of association (P<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (P<0.05) with rapid cycling.ConclusionThese results provide further evidence that variation in BDNF affects the risk for bipolar disorder.
| S-EPMC2653694 | biostudies-literature
Project description:IntroductionOur study was designed to examine the relationship between Brain-Derived Neurotrophic Factor (BDNF) genotypes (rs6265, Val66Met), BDNF plasma levels, and cognitive impairment in Chinese patients with panic disorder (PD).MethodsTotal 85 patients with PD and 91 healthy controls finally completed all assessments. The severity of panic symptoms and whole anxiety of PD was measured by Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Scale (HAMA-14). Montreal Cognitive Assessment (MoCA) and some neurocognitive measures were conducted to evaluate the cognitive performance. All participants were detected for the plasma BDNF levels and BDNF Val66Met polymorphism before assessment and treatment.ResultsNo significant differences were found in the BDNF allele frequencies and the BDNF genotype distributions between healthy controls and PD patients. BDNF Met/Met genotype was associated with lower BDNF plasma levels in PD patients, and PD patients with BDNF Met/Met genotype had the lower scores in the attention and speed of processing domains compared to those with Val/Val and Met/Val genotype (p's < .05). Among PD patients, the BDNF plasma levels showed moderate positive correlations with Stroop interference (r = .60, p < .001). Using the MoCA data, the BDNF plasma levels were correlated with delayed memory (r = .50, p < .001), verbal learning (r = .45, p < .001), and total scores of MoCA (r = .51, p < .001).ConclusionsThe BDNF Met/Met genotype may be associated with lower BDNF plasma levels and cognitive impairments in PD patients.
| S-EPMC7749616 | biostudies-literature
Project description:The brain-derived neurotrophic factor (BDNF) is a secretory growth factor that promotes neuronal proliferation and survival, synaptic plasticity and long-term potentiation in the central nervous system. Brain-derived neurotrophic factor biosynthesis and secretion are chrono-topically regulated processes at the cellular level, accounting for specific localizations and functions. Given its role in regulating brain development and activity, BDNF represents a potentially relevant gene for schizophrenia, and indeed BDNF and its non-synonymous functional variant, rs6265 (C ? T, Val ? Met) have been widely studied in psychiatric genetics. Human and animal studies have indicated that brain-derived neurotrophic factor is relevant for schizophrenia-related phenotypes, and that: (1) fine-tuned regulation of brain-derived neurotrophic factor secretion and activity is necessary to guarantee brain optimal development and functioning; (2) the Val ? Met substitution is associated with impaired activity-dependent secretion of brain-derived neurotrophic factor; (3) disruption of brain-derived neurotrophic factor signaling is associated with altered synaptic plasticity and neurodevelopment. However, genome-wide association studies failed to associate the BDNF locus with schizophrenia, even though a sub-threshold association exists. Here, we will review studies focused on the relationship between the genetic variation of BDNF and schizophrenia, trying to fill the gap between genetic risk per se and insights from molecular biology. A deeper understanding of brain-derived neurotrophic factor biology and of the epigenetic regulation of brain-derived neurotrophic factor and its interactome during development may help clarifying the potential role of this gene in schizophrenia, thus informing development of brain-derived neurotrophic factor-based strategies of prevention and treatment of this disorder.
| S-EPMC7386257 | biostudies-literature