Neuregulin 1基因多态性与中国汉族精神分裂症关联分析

目的 探讨Neuregulin 1(NRG1)基因多态性与精神分裂症的关联.方法 在258个中国汉族精神分裂症核心家系(患者及其亲生父母)中,应用实时定量PCR技术检测位于NRGl基因5'端的4个单核苷酸多态(single nucleotide polymorphism,SNP)位点:rs221533(C/T)、rs7820838(C/T)、433E1006 (A/G)和rs3924999(C/T),进行基因分型,应用传递不平衡检测(transmission disequilibrium test,TDT)分析等位基因传递情况,分析该基因与精神分裂症易感性的关联.结果 在258个中国汉族核心家系中,rs221533、433E1006、rs3924999三个SNP均存在有统计学意义的传递不平衡,优先传递的等位基因分别是:C、A、T(rs221533:X2=27.45,P=0.000;433E1006:X2=56.08,P=0.000;rs3924999:X2=10.53,P=0.001).rs7820838未检到不平衡传递(X2=3.31,P=0.081).频率大于1%单倍型进行分析,rs221533-rs7820838-433E1006联合分析,单倍型C/C/G和C/C/A优先传递(C/C/G:X2=5.26,P=45.08;C/C/A:X2=0.026,P=0.000);rs221533-rs7820838-433E1006-rs3924999联合分析,单倍型C/C/G/T、C/C/A/C和C/C/A/T优势传递(C/C/G/T:X2=10.71,P=0.001;C/C/A/C:.)X2=8.83,P=0.006、C/C/A/T:X2=27.00,P=0.000).213个阳性亚型的精神分裂症核心家系中传递不平衡得出基本一致的结果 .结论 Nrg1基因多态性与中国汉族人群精神分裂症存在关联,尤其是支持与阳性亚型精神分裂症存在关联.     

慢性精神分裂症事件相关电位P300与认知功能成套测验的研究

目的探讨慢性精神分裂症P300的波幅、潜伏期的变化,及其与认知功能成套测验的关系。方法检测41例慢性精神分裂症患者（患者组）及40名正常人（对照组）Cz、Fz、Pz 3点的P300,并用认知功能成套测验（MCCB）评定其认知功能。结果与正常对照相比,在Cz、Fz、Pz 3点,患者组P300波幅降低,潜伏期延长 患者组女性波幅明显比男性高。P300与MCCB相关分析显示,Fz潜伏期与连线、符号编码及持续操作呈负相关 Cz潜伏期与连线、符号编码、言语记忆及迷宫呈负相关 Pz潜伏期与符号编码、迷宫及视觉记忆呈负相关 Pz波幅与符号编码、空间广度、迷宫及视觉记忆呈正相关。结论P300及MCCB可以反映出额叶、顶叶及枕叶的情况,将神经生理学与神经心理学结合起来,说明他们可以从两方面共同对大脑认知功能做出评定。     

Neuregulin 1 gene and variations in perceptual aberration of schizotypal personality in adolescents

BACKGROUND: We test the hypothesis that the neuregulin 1 (NRG1 ) gene at chromosome 8p22-p12, which has been implicated as a susceptibility gene to schizophrenia, is associated with variations in schizotypal personality in non-clinical populations. METHOD: A randomly selected sample of 905 adolescents were assessed for their personality features using the Perceptual Aberration Scale (PAS) and the Schizotypal Personality Questionnaire (SPQ) and genotyped for three single nucleotide polymorphisms (SNP8NRG221533, rs3924999, and rs2954041) at the NRG1 gene. Relations between the three genetic variants and continuous schizotypal personality scores were evaluated using ANOVA for single-locus analyses and haplotype trend regression test for multi-locus analyses. RESULTS: Single locus analysis showed that the A allele of rs3924999, a functional polymorphism in exon 2, had the largest effect size and exhibited a prominent allele-dose trend effect for the PAS score. Haplotype analyses using the haplotype trend regression test indicated that the A allele of rs3924999 was mainly responsible for the association with the PAS but not with the SPQ or its three factors, and the magnitude of significance was not strengthened by the combination of this allele with adjacent locus. CONCLUSIONS: Our study provides the first evidence for the association of NRG1 with schizotypal personality and indicates a possible role of NRG1 in the genetic etiology of schizophrenia through perceptual aberrations.     

中国乒乓球听障奥运选手脑诱发电位特点的研究

探讨中国乒乓球听障奥运队员视觉诱发电位P100和事件相关电位P300的特点,为该项目运动员的选材和机能学评定提供参考。采用上海海神医疗电子仪器厂生产的NDI-200（海神号）神经电检诊仪,对参加2013年7月在保加利亚举行的第22届夏季听障奥林匹克运动会的8名中国乒乓球听障奥运选手和74名常人大学生的视觉诱发电位和视觉事件相关电位进行了记录、分析比较。奥运选手组和对照组之间视觉诱发电位P100波幅和潜伏期均无显著性差异（P＞0．05）。奥运选手组与对照组相比,视觉事件相关电位P300表现为：Cz点的波幅呈极显著性增加（P＜0．01）、Fz点的波幅呈显著性增加（P＜0．05）、Pz点的波幅有一定的增加（P＝0．061）;Pz点的潜伏期呈极显著性缩短（P＜0．01）;Pz、Cz、Fz点的反应时均呈极显著性缩短（P＜0．01）。听障乒乓球运动员和常人对照组之间视觉诱发电位P100波幅和潜伏期均无显著性差异;视觉事件相关电位P300表现为波幅增加、潜伏期缩短、反应时缩短的特点。     

老年慢性精神分裂症患者的听觉P300初步研究

应用丹表仪器，完成３４例患者和４０例正常老人的Ｐ３００检测。结果表明与正常老人比较，患者组靶潜伏期主成分（Ｎ１－Ｐ２－Ｎ２－Ｐ３）前移（Ｐ＜０．０１），靶波幅Ｐ２和Ｐ３降低（Ｐ＜０．０１）。非靶改变同靶刺激。提示老年慢性精神分裂症患者的听觉Ｐ３００仍有待进一步研究。     

老年慢性精神分裂症患者事件相关电位P300改变的意义

目的观察老年慢性精神分裂症(SCS)患者P300的变化.方法共有40例正常老人和34例SCS患者,应用丹麦仪器及两种短音刺激,完成P300检查.结果部分SCS患者波形有切迹.Fz、Cz和Pz三记录点比较无差异.N1靶潜伏期在额区右侧延长于左侧.与正常老人比较, SCS患者靶潜伏期主成分(N1-P2-N2-P3)前移(P＜0.01),靶波幅P2和P3降低(P＜0.01).非靶改变同靶刺激.结论P300可以辅助评定SCS患者的认知功能状态.     

Habituation of event-related potentials in patients with Parkinson's disease

Auditory event-related potential (ERP) was studied in idiopathic Parkinson's disease (PD) using our new procedures. We examined 12 non-demented patients with PD, and 9 age-matched control subjects. Ninety responses induced by rare stimulation were continuously recorded from Fz, Cz, Pz referred to linked earlobe electrode (A1A2), and were divided into nine blocks (one block = 10 responses) for statistical analysis. We assessed the habituation of auditory ERP to detect delicate changes related to the information processing in PD. N100 and P300 latencies were significantly longer in PD than in control subjects (p<0.05). P300 latency gradually increased with progression of recording blocks in both PD and control subjects, whereas N100 latency increased only in PD. Three way analysis of variance for P300 amplitude revealed significant effects of subject group, recording electrode site, and trial block. P300 amplitude was smaller in PD than in control subjects. Significant negative correlation between P300 amplitudes and block numbers were observed at Cz and Pz in PD, and at Fz in the control group. Previous reports as well as present results suggest that prolongation of N100 latency might be related to frontal lobe dysfunction, and abnormality of P300 to dysfunction in both the frontal lobe and hippocampus in PD.     

Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population

Results of gene expression microarray and quantitative PCR studies have suggested abnormalities in the expression of myelin-related genes including myelin-associated glycoprotein (MAG) in schizophrenic patients. Research provides strong evidence for oligodendrocyte dysfunction in schizophrenics. In order to further assess the role of MAG in schizophrenia, we examined four single nucleotide polymorphisms (SNPs), namely rs2301600, rs3746248, rs720309 and rs720308, of this gene in Chinese schizophrenic patients (n=470) and healthy controls (n=470). The distribution of rs720309 T/A genotypes showed a strong association with schizophrenia (chi(2)=14.58, d.f.=2, P=0.0008). A haplotype constructed of rs720309-rs720308 also revealed a significant association with schizophrenia (chi(2)=11.914, d.f.=3, P=0.0084). Our findings of a significant associations between schizophrenia and the MAG gene suggest that this gene may be involved in susceptibility to schizophrenia in the Chinese Han population.     

Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis.

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.     

Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.     

焦虑症患者VEP及AEP临床研究

目的：观察焦虑症患者听觉诱发电位(AEP)及视觉诱发电位(VEP)的特点。方法：对30例符合CCMD-Ⅱ-R诊断标准的焦虑症患者进行VEP和AEP检查，并以30例正常人作对照。结果：VEP在Fz及Cz处的P2、P3波幅明显降低，在Cz处N1潜伏期延长；AEP在Cz及P2处的P2、P3波波幅明显降低，N1潜伏期延长，在Cz处P2潜伏期延长。结论：焦虑症患者的VEP、AEP有波幅降低，潜伏期延长。     

Reliability analysis of event-related brain potentials to olfactory stimuli

Olfactory event-related potentials (OERP) have been used to investigate olfactory processing in health and disease. However, the reliability of the OERP has yet to be established statistically. The present study examined test-retest reliability of the OERP over a 4-week interval. EEG was recorded from Fz, Cz, and Pz, using a single-stimulus paradigm with amyl acetate. Reliabilities for ERP component latencies and interpeak amplitudes were assessed as intraclass and Pearson product-moment correlation coefficients. Reliabilities were higher for latency than for amplitude. Highest correlation coefficients were observed for P2 latency, specifically at Cz and Pz P3 amplitude and latency exhibited high reliability at Cz and Pz. Fz demonstrated weakest correlation coefficients. The data suggest that OERP reliability is comparable to that of auditory and visual ERPs, supporting the use of OERPs in both basic research and clinical assessment.     

The relationship between reaction time and response variability and somatosensory No-go potentials

We investigated the relationship between reaction time (RT) and response variability and somatosensory Go/No-go potentials. Event-related potentials following electrical stimulation of the second (Go stimulus) or fifth (No-go stimulus) digit of the left hand were recorded from 16 subjects, and Go and No-go stimuli were presented at an even probability. The subjects were instructed to respond to the Go stimuli by pushing a button with their right thumb. We analyzed the correlation between RT and the N140 and P300 components, and between the standard deviation (SD) of RT and the N140 and P300. Neither the amplitude nor latency of the No-go-N140 (N140 evoked by No-go stimuli) or the Go-N140 (N140 evoked by Go stimuli) related significantly with RT and the SD of RT. There was a significant negative correlation between RT and the amplitude of the No-go-P300 (P300 evoked by No-go stimuli) at Fz and C3, indicating that subjects with a shorter RT had a No-go-P300 of larger amplitude. The latency of the Go-P300 (P300 evoked by Go stimuli) at Pz and C3 showed a significant correlation with RT. The SD of RT was significantly correlated with the amplitudes of the No-go-P300 at C3 and Go-P300 at Pz and C4, and the latency of the No-go-P300 at Cz and Go-P300 at Fz, Cz, Pz, C3, and C4. Our results suggest that response speed and variability for the Go stimulus in Go/No-go paradigms affect No-go-related neural activity for the No-go stimulus.     

Association of catechol-O-methyltransferase gene polymorphisms with schizophrenia and negative symptoms in a Chinese population

The gene encoding Catechol-O-methyltransferase (COMT), a dopamine catabolic enzyme, has been associated inconsistently with schizophrenia in spite of consistent evidence for dopaminergic dysfunction in the prefrontal cortex (PFC) of schizophrenia. Since one contribution to this inconsistency might be genetic heterogeneity, this study investigated whether the COMT gene was associated with the development and symptoms of schizophrenia in relatively genetically homogeneous Chinese schizophrenic patients. We analyzed two polymorphisms (rs740603 and rs4818) of the COMT gene in a case-control study of 604 Han Chinese (284 patients and 320 controls). The patients' psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). We found no significant differences in the rs740603 and rs4818 genotype and allele distributions between the patient and control groups. Quantitative trait analysis by the UNPHASED program showed that the rs740603 and rs740603(G)-rs4818(G) haplotypes were associated with negative symptoms in the schizophrenic patients, particularly among female patients. Thus, the COMT gene polymorphisms may not contribute to the susceptibility to schizophrenia, but may contribute to the negative symptoms of schizophrenia among Han Chinese.     

The P300 component in patients with Alzheimer's disease and their biological children

OBJECTIVE: There are few studies examining P300 in the biological children of patients with Alzheimer's disease (AD). In addition to examining P300 in patients with AD, the current study examined the utility of P300 as a preclinical marker in the offspring of AD patients. METHODS: P300 was elicited from an AD group, their biological children, and two age- and gender-matched control groups using the auditory oddball paradigm. Each group consisted of 20 subjects each. ERPs recorded from sites Fz, Cz, and Pz were analysed using analysis of variance. RESULTS: Amplitudes were significantly smaller in the AD group when compared to controls. Both amplitude and latency values in the FH+ group were significantly impaired when compared to its control group. CONCLUSION: These findings replicate previous P300 amplitude abnormalities found in patients with AD. Further, participants with a family history of AD demonstrate possible preclinical evidence at the electrophysiological level. Comparisons with other findings and theoretical implications are discussed.     

Trk and cAMP-dependent survival activity of adenosine A(2A) agonist CGS21680 on rat motoneurons in culture

Schizophrenia is thought to arise in part from abnormal gray matter (GM), which are partly shared by the relatives of the probands. DISC1 is one of the most promising susceptibility genes of schizophrenia and a SNP rs821597 (A) in the gene was associated with schizophrenia in Han Chinese population. In this study, 61 healthy controls and 72 with schizophrenic patients were genotyped at rs821597, and underwent T1-weighted MRI for the density of GM. The results showed that the risk allele (A) carriers had higher GM density in regional left parahippocampal gyrus and right orbitofrontal cortex in schizophrenic patients, but had reduced GM density of these brain regions in healthy controls. The DISC1 variant rs821597 may confer risk for schizophrenia by its effects on the regional GM in left parahippocampal gyrus and right orbitofrontal cortex with other risk factors for schizophrenia.     

Association between FOXP2 polymorphisms and schizophrenia with auditory hallucinations

OBJECTIVE: A mutation in the FOXP2 gene has been the first genetic association with a language disorder. Language disorder is considered as a core symptom of schizophrenia. Therefore, the FOXP2 gene could be considered a good candidate gene for the vulnerability to schizophrenia. METHODS: A set of single nucleotide polymorphisms mainly located in the 5' regulatory region of the FOXP2 gene was analysed in a sample of 186 DSM-IV schizophrenic patients with auditory hallucinations and in 160 healthy controls. RESULTS: Statistically significant differences in the genotype (P=0.007) and allele frequencies (P=0.0027) between schizophrenic patients with auditory hallucinations and controls were found in the single nucleotide polymorphism rs2396753. These P values changed to 0.07 and 0.0273, respectively, after Bonferroni sequential correction. The haplotype rs7803667T/rs10447760C/rs923875A/rs1358278A/rs2396753A (TCAAA) also showed a significant difference confirmed with a permutation test (P=0.009). CONCLUSIONS: These results suggested that the FOXP2 gene may confer vulnerability to schizophrenic patients with auditory hallucinations.     

单胺氧化酶A基因多态性与精神分裂症的关联研究

目的探讨河南地区汉族人群单胺氧化酶A（monoamine oxidase A，MAOA）基因多态性与精神分裂症的关系。方法参照CCMD-3诊断标准，选取212例精神分裂症患者与168名正常对照，应用聚合酶链反应及限制性片段长度多态性技术检测MAOA基因多态性，采用病例一对照的关联分析方法对精神分裂症患者及正常对照的基因型和等位基因频率进行分析。结果（1）MAOA基因的基因型在患者组和对照组中均符合Hardy-Weinberg平衡定律（X^2=0．618，dr：2，P〉0、05；X^2=3．173，df=2，P〉0．05）。（2）MAOA基因的基因型和等位基因频率在患者组与对照组间的分布差异无统计学意义（P〉0．05）。（3）按性别分组，男性患者组中CT基因型分布频率显著高于男性对照组（X^2=7．654，P=0．022）。（4）MAOA基因的基因型和等位基因频率在家族史阴、阳性间的分布差异无统计学意义（P〉0．05）。结论没有发现MAOA基因多态性与汉族精神分裂症的发病有关联，但对性别发病有影响，基因型CT可能是男性精神分裂症发病的易感因素。     

The transmission disequilibrium analysis between neuronal nicotinic acetylcholine receptor alpha 7 subunit gene polymorphisms and schizophrenia]

OBJECTIVE: To investigate the association between neuronal nicotinic acetylcholine receptor alpha 7 subunit (CHRNA7) gene and schizophrenia. METHODS: The three polymorphisms rs2337980, rs1909884, rs883473 in CHRNA7 gene were detected based on PCR and polyacrylamide gel microarray in 129 schizophrenic trios. The results of genotyping were analyzed by haplotype relative risk analysis based on haplotype(HHRR), transmission disequilibrium test(TDT) and hyplotype analysis. RESULTS: (1)The HHRR analysis suggested that there was significant differences in rs2337980 allele frequencies between schizophrenia group and dummy control group(P= 0.017); (2)In TDT test, there may be transmission disequilibrium between rs2337980 and schizophrenia, the heterozygous parents excessively transferred the C allele to patients (P= 0.021); (3)The haplotype between rs2337980 and rs1909884 as well as the hyplotype among rs2337980, rs1909884 and rs883473 may have significant association with schizophrenia (global P= 0.034; global P= 0.027), the T-C and T-C-T hyplotype may have transmission disequilibrium with schizophrenia. CONCLUSION: There may be association between CHRNA7 gene polymorphisms and schizophrenia, the variant allele T in rs2337980 may have a protective effect to schizophrenia.