Brain-derived neurotrophic factor, sex hormones and cognitive decline in male patients with schizophrenia receiving continuous antipsychotic therapy

BACKGROUND There are systematic differences in clinical features between women and men with schizophrenia(SCZ).The regulation of sex hormones may play a potential role in abnormal neurodevelopment in SCZ.Brain-derived neurotrophic factor(BDNF)and sex hormones have complex interacting actions that contribute to the etiology of SCZ.AIM To investigate the influence of BDNF and sex hormones on cognition and clinical symptomatology in chronic antipsychotic-treated male SCZ patients.METHODS The serum levels of follicle-stimulating hormone,luteinizing hormone(LH),estradiol(E2),progesterone,testosterone(T),prolactin(PRL)and BDNF were compared between chronic antipsychotic-treated male(CATM)patients with SCZ(n=120)and healthy controls(n=120).The Positive and Negative Syndrome Scale was used to quantify SCZ symptoms,while neuropsychological tests were used to assess cognition.Neuropsychological tests,such as the Digit Cancellation Test(DCT),Semantic Verbal Fluency(SVF),Spatial Span Test(SS),Paced Auditory Serial Addition Test(PASAT),Trail Making Task(TMT-A),and Block Design Test(BDT),were used to assess executive functions(BDT),attention(DCT,TMT-A),memory(SS,PASAT),and verbal proficiency(SVF).RESULTS Although E2 levels were significantly lower in the patient group compared to the healthy controls,T,PRL,and LH levels were all significantly higher.Additionally,the analysis revealed that across the entire sample,there were positive correlations between E2 Levels and BDNF levels as well as BDNF levels and the digital cancellation time.In CATM patients with SCZ,a significant correlation between the negative symptoms score and PRL levels was observed.CONCLUSION Sex hormones and BDNF levels may also be linked to cognitive function in patients with chronic SCZ.

Differences in brain-derived neurotrophic factor gene polymorphisms between acute ischemic stroke patients and healthy controls in the Han population of southwest China

Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, Wes: China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological defici:s in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR]= 0.67;95% confidence interval [CI]: 0.45-1.00;P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65;95% CI: 0.42-1.00;P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.5& 95% CI: 0.37-0.90;P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008,4]) on July 25, 2008.

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

Brain-derived neurotrophic factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor(BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature.

The Biological Actions and Mechanisms of Brain-Derived Neurotrophic Factor in Healthy and Disordered Brains

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.

Effects of Risperidone and Paliperidone on Brain-Derived Neurotrophic Factor and N400 in First-Episode Schizophrenia

Background：Risperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor （BDNF） and N400 （an event-related brain potential component）.So far,different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments.However,few studies have been conducted on the mechanism ofrisperidone and paliperidone on BDNF and N400.This study aimed to compare the effects ofrisperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.Methods：Ninety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone,respectively,for 12 weeks.Serum BDNF level,the latency,and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale （PANSS） scores were compared between the two groups.Results：A total of 94 patients were included in the final analysis （47 patients in each group）.After the treatment,the serum BDNF levels in both groups increased （all P 〈 0.01）,while no significant difference in serum BDNF level was found between the groups before and after the treatment （all P 〉 0.05）.After the treatment,N400 amplitudes were increased （from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv,respectively） under congruent condition in both risperidone and paliperidone groups （all P 〈 0.01）.Under incongruent conditions,the N400 latencies were shortened in the paliperidone group （from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms,P 〈 0.05）,and the N400 amplitudes were increased in the risperidone group （from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv,P 〈 0.01）.After treatment,the total PANSS score in both groups decreased significantly （all P 〈 0.01）,but the difference between the groups was not significant （P 〉 0.05）.A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.Conclusions：Both risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function （N400 latency and amplitude）,but their antipsychotic mechanisms might differ.

Differential Relationships among Facets of Alexithymia and BDNF- and Dopamine-Related Polymorphisms

Alexithymia refers to a cluster of emotion-related deficits such as difficulty attending to and identifying one’s feelings. Although not a diagnosable psychiatric condition, alexithymia is considered a personality risk factor for multiple pathologies, including somatoform, substance use, eating, and mood disorders. Evidence suggests heritability, but few studies have examined the influence of specific genes on alexithymic traits. Candidate genes explored thus far include those involved in modulation of brain-derived neurotrophic factor (BDNF) and dopamine, two neurotransmitters whose functions have been implicated in human emotion processing. This study investigated the relationship between the C270T polymorphism of the BDNF gene, facets of alexithymia, and possible interactions with the COMT, DAT1, and ANKK1 genes in a sample of 130 healthy adults. Given the multidimensionality of the alexithymia construct and its overlap with the related constructs of emotional intelligence and mood awareness, we used principal components analysis to derive Clarity of Emotion and Attention to Emotion as specific facets of alexithymia. Results showed that the C270T C/C genotype group had lower Clarity of Emotion scores relative to the C/T genotype group, even after covarying for COMT, DAT1, and ANKK1 genotypes. Dopamine-related genes had no association with alexithymia dimensions, nor did they interact with the C270T polymorphism to predict Clarity of Emotion. Although the molecular mechanisms by which this polymorphism influences BDNF are unknown, this study suggests a role for BDNF in modulating aspects of alexithymia. We discuss these results in the context of BDNF’s trophic effects in the nervous system.

The roles of BDNF and ProBDNF in schizophrenia: possibilities for treatment

This review discusses the roles of brain-derived neurotrophic factor(BDNF)and precursor BDNF(proBDNF)in schizophrenia(SCZ).SCZ is associated with neuronal dysfunction,altered synaptic plasticity,and cognitive deficits.BDNF positively promotes neuronal growth,differentiation,and synapse forma-tion,and regulates synaptic transmission and plasticity.ProBDNF negatively affects neuronal survival and synaptic remodeling,however,by binding to its neurotroph-in receptor p75(p75NTR).A better understanding of the pathogenesis of SCZ vis-à-vis BDNF and proBDNF may provide new directions and strategies for its treatment.

脑源性神经营养因子基因C270T多态性与儿童精神分裂症的关系

目的探讨脑源性神经营养因子(BDNF)基因C270T多态性与儿童精神分裂症的关系。方法采用病例对照研究,用聚合酶链反应-限制性片段长度多态性方法,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;进行阳性与阴性症状量表(PANSS)评定,用Andreason阳性与阴性精神分裂症分型标准将患者分为阴性症状为主型(阴性组)和阳性症状为主型(阳性组)。结果①患者组和对照组间BDNF基因C270T多态性的基因型频率差异有统计学意义(2=24.56,P<0.01),前者的C/T型和T/T型频率高于后者;患者组等位基因T频率显著高于对照组(2=24.04,P<0.01);②阴性组、阳性组、对照组3组间基因型及等位基因分布的差异均有统计学义(2=37.93,P<0.01;2=38.90,P<0.01);两两比较显示,阴性组、阳性组分别与对照组比较,基因型及等位基因分布差异均有统计学义(P<0.001)。③不同基因型患者组之间PANSS各因子分和总分差异均无统计学意义(P>0.05)。结论BDNF C270T多态性与儿童精神分裂症有关,但与具体临床表现之间无明显的关系。

脑源性神经营养因子基因C270T多态性与精神分裂症的关联研究

目的研究脑源性神经营养因子(BDNF)基因C270T多态性与精神分裂症的相关性。方法运用聚合酶链反应技术检测194例精神分裂症和187例正常对照的BDNF基因C270T多态性的分布频率。结果精神分裂症的C/T和T/T基因型的分布频率分别为26.8%和14.4%;而对照组分别5.9%和2.7%,两组差异有显著性(P<0.05)。基因型为C/C或C/T患者在阴阳性症状量表阳性症状量表分,阴性症状量表分和一般精神病理分方面没有统计学意义。结论BDNF基因C270T多态性与精神分裂症相关。

儿童精神分裂症患者脑源性神经营养因子基因C270T多态性与脑室扩大及微小躯体异常的关系

目的调查儿童精神分裂症患者脑源性神经营养因子基因(BDNF)C270T多态性与脑室扩大及微小躯体异常(MPA)的关系。方法采用横断面研究的方法,用聚合酶链反应-限制性片段长度多态性方法,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;用CT测量患者的脑室值,采用Waldrop编制的躯体异常量表(WS)修改版评定MPA发生情况。结果①患者组BDNF基因C270T多态性的C/T和T/T基因型频率及T等位基因频率均高于对照组(2=24.56,P<0.01;2=24.04,P<0.01);②不同基因型患者组之间各脑室值比较差异均无统计学意义(P>0.05);T/T与C/T基因型患者合并后哈氏值高于C/C型患者(t=2.28,P<0.05);③T/T和C/T型合并后与C/C型患者比较,两组患者手部WS评分及WS总分的差异均具有统计学意义(Z=2.34,P<0.05;t=2.10;P<0.05);④WS总分与哈氏值及三脑室宽度存在正相关(r=0.26,P<0.01;r=0.29;P<0.01),与前角指数存在负相关(r=-0.18,P<0.05)。结论儿童精神分裂症患者BDNF基因C270T多态性与微小躯体异常有关,并可能与脑室扩大也有关。

BDNF基因rs6265多态性与首发精神分裂症患者伴发糖代谢异常的相关性研究

目的探讨脑源性神经营养因子(BDNF)基因rs6265多态性与首发精神分裂症发生糖代谢异常的关联性。方法首发精神分裂患者经OGTT试验区分为糖代谢异常者(研究组)与糖代谢正常者(对照组),分别收集120例,同时收集健康组120例。用高分辨率熔解曲线(HRM)对BDNFrs6265进行基因型检测,同时利用酶联免疫吸附技术测定血清BDNF水平。结果研究组AA基因型、A等位基因频率高于对照组(χ~2=9.82,P=0.00;χ~2=4.70,P=0.03)及健康组(χ~2=19.70,P=0.00;χ~2=8.16,P=0.03),差异有统计学意义。对照组与健康组的基因型及等位基因频率相比差异无统计学意义(χ~2=1.12,P=0.57;χ~2=0.50,P=0.48)。血清BDNF水平在各组中依次为研究组<对照组<健康组(F=40.09,P=0.00),3组中AA基因型BDNF水平均低于GG型、GA型(F=634.55,P=0.00,F=337.62,P=0.00,F=106.78,P=0.00)。结论 BDNF基因rs6265多态性与首发精神分裂症伴发糖代谢异常有关,且AA基因型是影响患者BDNF表达的因素之一。

脑源性神经营养因子基因3个SNPs位点与精神分裂症的相关性

目的研究脑源性神经营养因子(Brain-derived neurotrophic factor,BDNF)基因启动子区G-712A、外显子区C270T及Val66Met 3个SNPs位点与精神分裂症是否存在相关性。方法选取无亲缘关系的精神分裂症患者220例及健康对照组200例提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测G-712A、C270T和Val66Met 3个多态性位点的基因型,采用HaploView4.0及SPSS 11.5软件分析各位点基因型、等位基因频率及组间差异。结果 BDNF基因C270T位点的基因型及等位基因频率分布在精神分裂症组与正常对照组差异有统计学意义(P<0.05),精神分裂症组C270T位点的等位基因T频率高于正常对照组(χ2=7.573,P=0.006,OR=1.494,95%CI=1.122～1.990);G-712A和Val66Met位点的基因型及等位基因频率分布在精神分裂症组与正常对照组无统计学意义(P>0.05)。结论 BDNF基因C270T多态性可能与精神分裂症有关,携带有C270T多态性位点T等位基因的个体可能更容易患精神分裂症。

GDNF基因多态性与精神分裂症临床特征的相关性

目的探讨GDNF基因多态性与精神分裂症临床特征的相关性。方法对符合纳入标准的精神分裂症病例组及健康对照组进行临床资料收集及血样的采集,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测GDNF基因多态性。选取GDNF基因2个SNP位点:rs2973050,rs2910702。所有数据应用SSPS13.0软件包处理。结果①哈迪温伯格平衡(Hardy-Weinberg s equilibrium)结果显示,GDNF基因rs2910702在病例组中偏离哈迪温伯格平衡(χ2=24.983,P=0.000);②GDNF等位基因频率在病例组与对照组中的分布无统计学差异(P>0.05),但基因型频率分布有统计学差异(P<0.05);③GDNF各基因型与精神分裂症的临床分型、PANSS量表各因子分无明显相关性。结论 rs2973050基因型C/C、rs2910702基因型G/G可能与精神分裂症的发生有关,为精神分裂症的危险基因型。

精神分裂症患者BDNF基因C270T多态性Meta分析

目的评价脑源性神经营养因子基因C270T多态性与精神分裂症的关系。方法检索国内外公开发表的关于精神分裂症患者C270T位点多态性病例对照研究的文献,对C270T位点C/T等位基因和CC/(CT+TT)基因型进行Meta分析,计算OR值,并按人种因素分亚组分析。结果共纳入16篇文献,包括3874例患者与4309名对照。C/T等位基因和CC/(CT+TT)基因型均与精神分裂症有关(均P<0.01),OR值分别为1.65[95%CI(1.26,2.16)]和1.71[95%CI(1.27,2.30)]。亚组分析中,高加索人群等位基因和基因型与精神分裂症无统计学关联(均P=0.05);亚洲人群等位基因和基因型与发病风险有关(均P<0.01),OR值分别为1.89[95%CI(1.30,2.75)]和1.97[95%CI(1.29,3.03)]。结论脑源性神经营养因子基因C270T位点多态性可能增加亚洲人群精神分裂症的易感性。

脑源性神经营养因子基因多态性与精神分裂症的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因多态性与精神分裂症的关联性。方法:以111例精神分裂症发作期患者与362例正常对照为研究对象,通过TaqM an探针单核苷酸多态性(SNP)基因分型技术对BDNF基因及基因上游10 kb区域的标签SNPs rs6265和rs11030101进行基因分型,比较各组间基因型、等位基因及联合基因型分布频率。结果:精神分裂症患者(n=107)与正常对照(n=357)的SNPs rs6265和rs11030101基因型、等位基因及联合基因型分布频率差异无统计学意义;患者发病年龄、不同临床分型与正常对照的基因型、联合基因型之间比较差异无统计学意义。治疗4周后,SNPrs6265的G/G型、G/A型及A/A型阳性与阴性症状量表(PANSS)阴性分量表分依次为(16.38±8.17)、(12.63±4.32)及(12.60±5.08)(F=3.442,P=0.037)。治疗4周个人和社会功能量表(PSP)评分的升幅依次为(37.60±17.96),(25.25±19.18)及(22.90±15.44)(F=4.129,P=0.020)。结论:精神分裂症患者SNPs rs6265和rs11030101基因多态性与精神分裂症发病年龄、临床分型、急性期症状无关,但rs6265的A/A基因型患者在治疗后阴性症状及社会功能的改善较其他基因型患者显著。

脑源性神经营养因子基因多态性与精神分裂症及其认知功能的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因多态性与中国汉族精神分裂症(SCZ)发病及其认知功能的关系。方法:对354例SCZ患者(SCZ组)和416名健康对照人群(正常对照组)的BDNF基因4个多态性位点(rs7482257、rs7483883、rs1491850、rs16917234)进行基因分型;采用重复性成套神经心理状态测验(RBANS)对SCZ组及正常对照组进行认知功能评估。结果:SCZ组RBANS注意分、言语分、视觉广度分、即刻记忆分、延迟记忆分及总分明显低于正常对照组(F=1. 40,F=16. 38,F=96. 99,F=41. 12,F=114. 40,F=65. 23; P均<0. 001)。两组BDNF基因4个多态性位点的等位基因(χ2=0. 37～2. 80)、基因型(χ2=1. 06～5. 77)及单体型(χ2=0. 224～2. 979)分布频率比较差异无统计学意义(P均> 0. 05)。在SCZ组中,BDNF基因rs7482257不同基因型间视觉广度因子评分差异有统计学意义(F=3. 79,P=0. 024)。结论:BDNF基因多态性可能与SCZ易感性无关联; BDNF基因rs7482257位点的CC基因型可能与SCZ的视觉广度损害有关。

精神分裂症脑源性神经营养因子基因C270T多态性与利培酮临床疗效的关联性研究

目的观察脑源性神经营养因子(BDNF)基因C270T多态性与利培酮临床疗效的关联性。方法将104例首发精神分裂症患者按C270T多态性分为C/C组65例和C/T+T/T组39例。所有患者均予以利培酮治疗,根据病情逐步调整,最大剂量不超过8 mg·d^(-1)。于治疗前及治疗后1个月后用阳性和阴性症状评定量表(PANSS)评估精神症状,比较2组患者精神症状的改善情况。结果 BDNF基因C270T多态性分布情况:C/C型65例(62.5%)、C/T型36例(34.6%)、T/T型3例(2.9%);等位基因分布情况:C等位基因166个(79.8%)、T等位基因42个(20.2%)。治疗1个月后,2组患者的PANSS的阳性评分、阴性评分及总分均较治疗前显著下降(P<0.05),且C/C组PANSS阳性评分、阴性评分及总分的减分率均明显优于C/T+T/T组(P<0.05)。结论利培酮对不同C270T基因亚型的精神分裂症患者均能发挥治疗效果,但对C/C型患者的疗效更好,而对C/T+T/T型患者疗效相对偏差。

脑源性神经营养因子基因多态性与早发精神分裂症的关联分析

目的探讨中国汉族人群脑源性神经营养因子（BDNF）基因rs11030101和rs6265多态性与早发精神分裂症的关联性。方法采用TaqMan法，检测360例早发精神分裂症患者（患者组，起病年龄〈18岁）和399名健康对照（对照组）BDNF基因rs11030101及rs62652个多态位点，并对等位基因、基因型及单体型频率进行比较。结果（1）患者组与对照组rs11030101等位基因分布和基因型分布的差异均有统计学意义[X^2=5．13，自由度（df=1，P=0．024；X^2=6．12，df=2，P=0．047]，但经Bonferrpmo校正检验后，只有等位基因分布的差异有统计学意义（P=0．048）；单体型分析显示，患者组与对照组A—Val及T—Val分布的差异有统计学意义（X^2=7．96，P=0．005；X^2=8．53，P=0．004）。（2）在女性人群中，患者组与对照组rs11030101基因型分布的差异有统计学意义（X^。=7．76，df=2，P=0．021），经Bonferroni校正检验后差异仍有统计学意义（P=0．042）；单体型T—Val及T—Met分布的差异均有统计学意义（X^2=6．90，P=0．009；X^2=4．60，P=0．032）。结论在中国汉族人群中BDNF基因可能与早发精神分裂症存在关联，尤其与女性早发精神分裂症存在关联，其可能是女性早发精神分裂症的易患基因。

脑源性神经营养因子Va166Met基因多态性与首发精神分裂症临床特征的关联研究

目的探讨脑源性神经营养因子（brain—derivedneurotrophicfactor，BDNF）基因Val66Met多态性与首发精神分裂症临床特征的关联性。方法应用TaqMan荧光探针技术对135例首发精神分裂症患者及483名正常对照者进行基因分型；采用阳性与阴性症状量表（positiveandnegativesyndromescale，PANSS）评估精神分裂症患者临床特征。结果精神分裂症患者组与正常对照组BDNFVal66Met基因型及等位基因分布频率的差异具有统计学意义（P〈0．01）；Met／Met基因型患者的PANSS总分、焦虑（抑郁）因子分及认知损害因子分均高于Val／Val和Val／Met基因型患者，差异有统计学意义（P〈0．01）。结论BDNF基因Val66Met多态性可能与精神分裂症的发病有关；首发精神分裂症患者中Met／Met基因型者临床症状可能更重。