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The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia.

ABSTRACT: OBJECTIVE:Brain-derived neurotropic factor (BDNF) is widely distributed in the peripheral and central nervous systems. BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of several mental illnesses. To elucidate the role of BDNF, we compared the plasma BDNF levels and the BDNF Val66Met gene variants effect in several mental disorders. METHOD:We enrolled 644 participants: 177 patients with bipolar I disorder (BP-I), 190 with bipolar II disorder (BP-II), 151 with schizophrenia, and 126 healthy controls. Their plasma BDNF levels and BDNF Val66Met single nucleotide polymorphisms (SNP) were checked before pharmacological treatment. RESULTS:Plasma levels of BDNF were significantly lower in patients with schizophrenia than in healthy controls and patients with bipolar disorder (F = 37.667, p<0.001); the distribution of the BDNF Val66Met SNP was not different between groups (?(2) = 5.289, p = 0.507). Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not influence plasma BDNF levels in our participants. Plasma BDNF levels were, however, significantly negatively correlated with depression scores in patients with bipolar disorder and with negative symptoms in patients with schizophrenia. CONCLUSION:We conclude that plasma BDNF profiles in different mental disorders are not affected by BDNF Val66Met gene variants, but by the process and progression of the illness itself.

SUBMITTER: Chen SL

PROVIDER: S-EPMC7137229 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia.

Chen Shiou-Lan SL Lee Sheng-Yu SY Chang Yun-Hsuan YH Chen Shih-Heng SH Chu Chun-Hsien CH Wang Tzu-Yun TY Chen Po-See PS Lee I-Hui IH Yang Yen-Kuang YK Hong Jau-Shyong JS Lu Ru-Band RB

Progress in neuro-psychopharmacology & biological psychiatry 20140125

<h4>Objective</h4>Brain-derived neurotropic factor (BDNF) is widely distributed in the peripheral and central nervous systems. BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of several mental illnesses. To elucidate the role of BDNF, we compared the plasma BDNF levels and the BDNF Val66Met gene variants effect in several mental disorders.<h4>Method</h4>We enrolled 644 participants: 177 patients with b ...[more]

PMID: 24468644

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Project description:BackgroundBrain-derived neurotrophic factor (BDNF) is a candidate for susceptibility locus of Panic disorder (PD). However, the findings about the role of the BDNF Val66Met variant in PD were not consistent. Till now, the relationship between BDNF Val66Met polymorphism and anxiety-related traits in PD patients has been rarely explored. This study aimed to explore the relationship among BDNF Val66Met polymorphism, plasma BDNF level and anxiety-related trait in Chinese PD patients.MethodThis multi-center study included 116 PD patients and 99 health controls. We detected single-nucleotide polymorphism (SNP) of BDNF rs6265 (Val66Met) and BDNF plasma level in the two groups. In addition, PD patients were administered the State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Rating Scale (HAMA-14). Quantitative comparison of the differences of BDNF concentration among subjects with different genotypes and association between BDNF Val66Met genotype and trait anxiety were performed.ResultsThere were no significant differences in the genotype frequency (p = 0.79) or allele frequency (p = 0.88) between PD patients and health controls. BDNF plasma levels of PD patients were significantly lower than those in control group (p = 0.003). BDNF plasma levels of the Met/Met genotype were significantly lower than those of Val/Met genotype in PD patients (p = 0.033). PD patients carried Met/Met genotype showed significantly higher scores in STAI trait compared to those carried Val/Val genotype (p = 0.045) and Val/Met genotype (p = 0.018). STAI trait scores of PD patients with agoraphobia were significantly higher than those of patients without agoraphobia (p < 0.05). The ANCOVA showed that the dependent variable STAI trait score was significantly affected by factor "genotype" (Val/Val, Val/Met, Met/Met, p = 0.029), and covariate "agoraphobia" (p = 0.008). In this model, 11.5% of the variance of the STAI trait score was explained by the BDNF genotype. Contrast analysis showed STAI trait scores of Met/Met subjects were significantly higher than those of Val/Met (p = 0.018) and Val/Val individuals (p = 0.045).ConclusionWe found that anxiety trait was associated with the BDNF polymorphism in PD patients. BDNF Met/Met genotype may decrease plasma BDNF level and increase trait anxiety in panic disorder.

Project description:A novel susceptibility locus (rs11098403) for schizophrenia and bipolar disorder (BD) was identified in an Ashkenazi Jewish population by a recent large-scale genome-wide association study. The rs11098403 is located in the vicinity of the gene encoding N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3, (NDST3). This study aimed to replicate the results in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association of NDST3 with the schizophrenia and BD risk in the Han Chinese. In stage 1, a total of 632 patients with schizophrenia, 654 patients with BD and 684 healthy controls were recruited from the Shanghai region. In stage 2, 522 schizophrenia patients and 547 normal subjects were enrolled from the Hangzhou region. Then, we conducted a meta-analysis based on the present literature. In stage 1, the single nucleotide polymorphism (SNP) rs11098403 showed a significant association with schizophrenia (corrected P=0.005). The frequency of the rs11098403 G allele was significantly lower among schizophrenia patients than among the controls (odds ratio (OR)=0.68, 95% confidence interval (CI): 0.55-0.84, corrected P=0.002). No significant difference was observed in individual SNP marker genotypes or allele distributions between the BD and control groups. In stage 2, the association of rs11098403 with schizophrenia could be validated (genotypic P=0.001 and allelic P=0.0003). After pooling all data from 1861 patients with schizophrenia and 2081 controls, we observed a significant association of the rs11098403 G allele with schizophrenia (Z=5.56, P<0.001), with an OR=0.70 (95% CI: 0.61-0.79). Then, we performed an expression quantitative trait loci analysis to investigate the functional effect of rs11098403 on NDST3 expression in the brain. We observed a significant association of rs11098403 with NDST3 expression in the hippocampus (P=0.027), although the significance did not survive after multiple testing correction. Our findings provided preliminary evidence that rs11098403 might modify the genetic risk of schizophrenia in the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brain NDST3 expression in the Han Chinese. These results would help to explain the pathophysiological mechanism of schizophrenia.

Project description:BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

Dataset Information

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia.

Publications

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia.

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