5-羟色胺转运体基因多态性与精神分裂症的相关性研究

目的：探讨中国汉族人群中5一羟色胺转运体（5-HTT）基因与精神分裂症之间的相关性。方法：189例符合中国精神障碍分类与诊断标准第3版及美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者（患者组）使用聚合酶链式反应扩增5-HTT基因的启动子区（5-HTrLPR）位点和内含子区（5-HTTVNTR）位点,以琼脂糖凝胶电泳分离法进行基因分型,并和300名正常人（正常对照组）进行对照。结果：患者组与正常对照组之间5-HTTLPR位点L／L、L／S和S／S基因型频率以及等位基因L、s频率分布上差异具有统计学意义（x2=47．882,x2=44．188;P〈0．01或P〈0．001）;5-HTTVNTR位点12／12、12／10、10／10基因型频率和等位基因10、12频率分布上差异无统计学意义（X2=0．335,X。=0．051;P均〉0．05）。结论：S／S基因型及S等位基因可能是精神分裂症患者的易感等位基因;5-HT．TVNTR位点在中国汉族人群精神分裂症发病机制中可能不起主要作用。     

5羟色胺转运体启动子区CpG岛甲基化与精神分裂症的相关研究

目的探讨5羟色胺转运体(5-HTT)启动子区CpG岛甲基化水平与精神分裂症的相关性。方法纳入符合美国精神障碍诊断与统计手册第Ⅳ版(DSM-IV)诊断标准的首发精神分裂症患者30例和正常对照30名,采用亚硫酸氢钠测序法测定受试者的5-HTT基因启动子区CpG岛甲基化水平。结果患者组和正常对照组间5-HTT基因启动子区CpG岛甲基化水平的差异无统计学意义(2=0.25,P0.05);以两组的平均年龄27岁分层后再比较,患者组和对照组相同年龄段的5-HTT基因启动子区CpG岛甲基化水平差异亦无统计学意义(P0.05),按性别分组后比较,患者组和对照组间的差异也无统计学意义(P0.05)。结论本研究未发现5-HTT基因启动子区CpG岛甲基化水平与精神分裂症相关。     

5-羟色胺转运体基因多态性与SSRIs疗效

本文就5-羟色胺转运体多态性与SSRIs疗效之间关系作一综述。     

5-羟色胺转运体基因多态性与SSRIs疗效

本文就 5 -羟色胺转运体多态性与 SSRIs疗效之间关系作一综述。     

儿童孤独症与5-羟色胺转运体基因连锁多态性区域的关联性研究

目的:探讨汉族人群中5-羟色胺转运体基因连锁多态性区域(5-HTTLPR)与儿童孤独症(CA)的相关性. 方法:采用病例对照研究、聚合酶链反应(PCR)的方法对中国汉族CA患儿与5-HTTLPR的关联性进行研究.以健康儿童作对照. 结果:中国汉族CA患者的5-HTTLPR分布与对照组差异无显著性,但CA组5-HTTLPR纯合子基因型的频率显著高于对照组;5-HTTLPR的基因型与CA的躯体运动因子显著相关. 结论:5-HTTLPR与CA的主要症状存在显著关联;5-HTTLPR的纯合子基因型和等位基因L可能增加了CA的患病危险.     

五羟色胺转运体启动子区CpG岛甲基化与精神分裂症的相关性研究

本文综述了DNA甲基化及5羟色胺转运体与精神分裂症的研究进展。通过分析三者之间的相关性,指出了精神分裂症发病原因的可能研究方向。     

5-羟色胺转运体基因第二内含子多态性与强迫症的关联分析

目的　探索上海地区汉族人口中 5 羟色胺转运体 ( 5 HTT)基因第二内含子多态性与强迫症的关系。方法　采用聚合酶链反应扩增片段长度多态 (PCR AmFLP)技术测定 10 2例强迫症 (OCD)患者和 110名健康对照的基因型。结果　强迫症患者 5 HTT第二内含子基因型与等位基因分布与健康对照之间均存在显著性差异 (P <0 0 5 ) ;等位基因 10和 12 / 10基因型与强迫症存在显著正关联 (OR值分别为 2 4 5和 2 4 2 ,P <0 0 5 )。结论　汉族人群中 5 HTT基因第二内含子多态性与强迫症的发病可能有遗传关联 ,等位基因 10和 12 / 10基因型可能是强迫症的风险因子     

5-羟色胺转运体基因多态性与自杀未遂的关联研究

目的探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与自杀未遂的关系。方法运用聚合酶链反应技术(PCR)检测71例自杀未遂患者和80名健康对照5-HTTLPR基因型。结果自杀未遂组与对照组5-HTTLPR的基因型及等位基因(S/L)频率差异无统计学意义(P>0.05);进一步分析显示,有精神疾病自杀未遂组(37例)的短重复序列S等位基因频率为85.1%,与正常对照组(72.5%)及无精神疾病自杀未遂组(69.1%)的差异均具有统计学意义(X2=4.49,P=0.04;X2=5.21,P=0.03)。结论5-HTTLPR的S等位基因和精神病自杀未遂存在关联。     

广泛性焦虑障碍与5-羟色胺转运体基因多态性的相关研究

目的　探讨广泛性焦虑障碍与 5 羟色胺转运体 (5 HTT)基因启动子区和内含子 2区两种多态性的相关性。方法　运用聚合酶链反应技术检测 4 7例广泛性焦虑障碍患者 (患者组 )和 90名健康对照者 (对照组 )两种基因多态性的分布频率。结果　患者组启动子区多态性 (5 HTTLPR)的short/short(SS)基因型和short(S)等位基因频率分别为 72 %和 83% ,对照组SS基因型和S等位基因频率分别为 4 9%和 71% ,两组间的差异有显著性 (P <0 0 5 )。内含子 2区数目可变的顺向重复多态性各基因型 (12 / 12 ,12 / 10 ,10 / 10 )频率在患者组中分别为 72 % ,2 6 % ,2 % ,在对照组中分别为 78% ,2 1% ,1% ,两组间的差异无显著性 (P >0 0 5 ) ;等位基因频率比较的差异亦无显著性 (P >0 0 5 )。结论　 5 HTTLPR的SS基因型可能是广泛性焦虑障碍的易感基因之一。     

强迫症与5-羟色胺转运体基因多态的关联分析

目的 探索汉族人群中5-羟色胺转运体SLC6A4基因多态与强迫症发病的关系。方法采用聚合酶链反应扩增片段长度多态技术测定120例强迫症患者(强迫症组)和130名健康人(对照组)的SLC6A4基因型。结果 强迫症组SLC6A4第2内含子及启动子的基因型多态分布与对照组间的差异有显著性(X2=6.70,P=0.035;X2=6.35,P=0.042);第2内含子等位基因频数分布与对照组之间的差异有非常显著性(X2=7.54,P=0.006);第2内含子的等位基因10,12/10基因型和启动子的L/L基因型与强迫症存在显著正关联[比数比(OR)值分别为2.24,2.12和3.57,P<0.05];强迫症组及对照组内不同性别间基因型分布的差异均无显著性(P>0.05)。结论 在汉族人群中SLC6A4基因可能与强迫症存在遗传关联,第2内含子的等位基因10和12/10基因型、启动子的L/L基因型可能是强迫症的风险因子。     

Electroconvulsive shock regulates serotonin transporter mRNA expression in rat raphe nucleus

The antidepressive actions of electroconvulsive shock (ECS) therapy are considered to involve altered neurotransmission of serotonin. In this study, we investigated the effects of acute and chronic ECS on 5-hydroxytryptamine (5-HT) transporter mRNA expression in rat raphe nucleus. We found that serotonin transporter (5-HTT) mRNA expression was decreased in 9 and 24 h after acute ECS and in 3, 9, 24 h and 2 weeks after chronic ECS in rat raphe nucleus. We presume that the adaptive change in 5-HTT mRNA expression is possibly related to the therapeutic efficacy of electroconvulsive therapy (ECT) on medication-resistant depression.     

Blood serotonin levels in suicidal schizophrenic patients

A decrease in central serotonin metabolism has been found in suicidal patients. In schizophrenic patients suicidality is predominantly observed as a transient phenomenon being most pronounced during an acute psychotic episode. We investigated blood serotonin levels as a paradigm for serotonin metabolism in suicidal schizophrenic women who were psychotic and compared their data with those of nonsuicidal psychotic schizophrenic women and healthy controls. Blood serotonin was lower in suicidal female schizophrenic patients (0.44 +/- 0.05 mumol/l, n = 17) than in nonsuicidal female schizophrenic patients (0.94 +/- 0.07 mumol/l, n = 17; P less than 0.001) or in healthy women (0.90 +/- 0.02 mumol/l, n = 26; P less than 0.001). These findings support the hypothesis that decreased serotonin metabolism may be associated with suicidal behavior in schizophrenic women.     

Platelet serotonin transporter in stroke patients

OBJECTIVES: Post-stroke depression can be treated with serotonin transport inhibitors suggesting a role for the serotonin system in these patients. The number of platelet serotonin transporters in stroke patients and in control subjects have been measured in this study. MATERIAL AND METHODS: Newly admitted stroke patients who did develop or who did not develop a post-stroke depression, non-acute patients who previously had had a stroke and control subjects were compared. The number of platelet serotonin transporters was analysed by ligand binding methodology. RESULTS: The number of platelet serotonin transporters was low shortly after a stroke compared with normal subjects; no difference was found between the stroke patients who developed a post-stroke depression and those who did not. CONCLUSION: A low number of platelet serotonin transporters may be a non-specific state marker for a condition as acute stroke.     

Identification of serotonin transporter mRNA in rat platelets

Summary Total RNA was isolated from rat platelets by guanidinium — acid —phenol extraction, and mRNA for the serotonin (5-hydroxytryptamine) transporter (5HTt) was identified. From a typical starting sample of 20mL of rat blood (9 × 10⁹ platelets), 14 to 17g of total platelet RNA was obtained. Northern blot analysis, using³²P-labeled 5HTt cDNA as a probe, identified 3.3 kb long 5HTt mRNA. After rehybridization with cyclophilin cDNA, 1kb long mRNA for cyclophilin, which could serve as a reference for 5HTt mRNA quantification, was also identified. Densitometric analysis demonstrated clearly measurable signals for both mRNAs. The possibility of quantification of rat platelet 5HTt mRNA should enable parallel studies on 5HTt gene expression in platelets and brain of the same animal, and the evaluation of the platelet model at the molecular genetic level.     

Brain serotonin transporter binding in non-depressed patients with Parkinson's disease

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [¹¹C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (−22%), caudate (−30%), putamen (−26%), and midbrain (−29%). However, only a slight non-significant reduction (−7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.     

Platelet serotonin transporters and the transporter gene in control subjects, unipolar patients and bipolar patients

OBJECTIVE: The purpose of the present study was to relate the number of platelet serotonin transporters in unipolar and bipolar patients and in control subjects to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a deletion/insertion in the promoter region. METHOD: Density of platelet serotonin transporters was determined by radioligand binding analysis. Genotyping was performed by PCR amplification of polymorphic regions followed by size determination of the obtained fragments. RESULTS: The control subjects and the two groups of patients were similar with respect to the genotype and allele distribution belonging to the two polymorphisms in the serotonin transporter gene for. An interaction between status (control, unipolar- or bipolar patient) and VNTR genotype regarding the number of platelet serotonin transporters was observed; unipolar patients with the genotype 12/10 had more platelet serotonin transporters than bipolar patients and controls with this genotype. No association related to the polymorphism was found in the promoter region of the serotonin transporter gene. CONCLUSION: An association was observed between the polymorphism in intron 2 of the serotonin transporter gene and the number of platelet serotonin transporters. Unipolar patients with a particular genotype had more platelet serotonin transporters than the corresponding controls and bipolar patients.     

Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis.

BACKGROUND: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains. METHODS: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type. RESULTS: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p =.001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p =.001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis. CONCLUSIONS:The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.     

A comparative uptake study of serotonin, dopamine, and norepinephrine by platelets of acute schizophrenic patients

Active uptake of serotonin, dopamine, and norepinephrine by blood platelets of 22 acute schizophrenic patients and 15 normal control subjects was studied over a 6-week period. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the subjects' mental state over this period. Serotonin uptake by platelets of the schizophrenic group was 40% lower than that by platelets of the control group (p less than 0.001). No significant differences in uptake of dopamine or norepinephrine were observed. These results might reflected a genetic defect in the schizophrenic patients. No significant correlations were found between the biochemical and BPRS results. A correlation was found between the uptake results with dopamine and norepinephrine but not between these amines and serotonin. This finding may provide indirect support for previously published experimental data which suggest that the carriers to dopamine and norepinephrine differ in function from those of serotonin.     

精神分裂症患者多巴胺D2受体和多巴胺转运体基因表达水平与临床症状的关系

目的 探讨精神分裂症患者外周血淋巴细胞多巴胺D2受体(DRD2)和多巴胺转运体(DAT)的mRNA表达水平与精神分裂症临床症状的关系.方法 以实时荧光定量逆转录-聚合酶链反应技术检测治疗前精神分裂症组(25例)、长期服药(氯氮平)慢性精神分裂症组(27例)和对照组(30名)外周血淋巴细胞中DRD2和DAT的mRNA表达水平,同时对精神分裂症患者的阳性和阴性症状量表(PANSS)进行评定,并采用Spearman分析二者的相关性.结果 治疗前精神分裂症组、长期服药慢性精神分裂症组、对照组样本外周血淋巴细胞DRD2的基因表达水平分别为0.32±0.13、0.37±0.19、0.34±0.09,3组比较差异无统计学意义(F=0.510,P＞0.05);DAT的基因表达水平分别为0.48±0.24、0.58±0.21、0.39±0.24,3组比较差异有统计学意义(F=4.330,P＜0.05);长期服药慢性精神分裂症组DAT基因表达水平显著高于对照组(MS组内=0.194,P ＜0.01);治疗前精神分裂症组DRD2基因表达水平与PANSS阳性症状分呈显著正相关(r=0.443,P＜0.05),DAT基因表达水平与PANSS总分(r=-0.418,P=0.075)、一般病理症状分(r=-0.434,P=0.063)的相关性未达统计学意义.结论 精神分裂症患者外周血淋巴细胞DRD2的基因表达水平与PANSS量表的阳性症状分显著正相关,而精神分裂症患者外周血淋巴细胞DAT的基因表达水平可能受氯氮平影响上调.