多巴胺D2受体基因多态性与利培酮疗效、锥体外系副反应及治疗前后泌乳素水平变化的关联分析

目的 探讨多巴胺D2受体基因Tqq1A多态性与利培酮的疗效、锥体外系副反应及治疗前后泌乳索水平变化的相关性.方法 纳入198例首发精神分裂症患者和198名健康对照,给予患者利培酮治疗8周;采用阳性和阴性症状量表和修改的Sampson氏锥体外系反应量表分别评定患者的疗效和锥体外系副反应(EPS);测定患者治疗前后泌乳素水平;检测所有受试者的D2受体基因Taq1 A多态性.结果 不同疗效组、有无EPS组的Taq1 A多态性基因型和等位基因频率差异均无统计学意义(P>0.05),不同基因型组和不同等位基因组患者之间治疗前后泌乳素升高的差异无统计学意义(P>0.05).结论 未发现D2受体基因Taq1 A多态性与利培酮的疗效、锥体外系副反应及治疗前后泌乳素变化存在关联.     

精神分裂症患者MDR1C3435T基因多态性与帕利哌酮疗效的相关性

目的:研究精神分裂症患者MDR1C3435T基因多态性与帕利哌酮缓释片疗效的相关性。方法:收集服用非典型抗精神病药物帕利哌酮缓释片患者68例,采用阳性和阴性症状量表(PANSS)评定疗效,个人与社会功能量表(PSP)评定社会功能,根据PANSS减分率(≥50%为有效)分为有效组和无效组。采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测其MDR1C3435T位点的基因型。将有效组和无效组的基因型进行卡方检验。结果:治疗前后PANSS及PSP量表评分比较差异有统计学意义(P<0.001),有效组与无效组基因型差异无统计学差别(P>0.05)结论:帕利哌酮缓释片治疗精神分裂症疗效肯定,未发现MDR1C3435T基因多态性与帕利哌酮的疗效有关。     

非典型抗精神病药对男性精神分裂症患者勃起功能及血浆催乳素水平的影响

目的:探讨非典型抗精神病药(AAP)对恢复期男性精神分裂症患者勃起功能及血浆催乳素(PRL)水平的影响。方法:采用国际勃起功能指数-5问卷(IIEF-5)对以氯氮平、喹硫平、奥氮平、利培酮、阿立哌唑、氨磺必利、帕利哌酮及齐拉西酮单一治疗≥6个月、具有稳定性伴侣的恢复期男性精神分裂症患者各30例进行总体勃起功能障碍(ED)评定,以IIEF-5≤21分定义为ED;同时采用放免法检测患者的血浆PRL水平。结果:ED发生率氨磺必利组显著高于氯氮平组、喹硫平组及阿立哌唑组(P均0.001),利培酮组显著高于阿立哌唑组(P0.01)。血浆PRL水平氨磺必利组、齐拉西酮组及利培酮组显著高于氯氮平组、喹硫平组、奥氮平组及阿立哌唑组(P均0.001),帕利哌酮组显著高于阿立哌唑组(P0.001)。IIEF-5评分与全部患者及氨磺必利组、帕利哌酮组和齐拉西酮组血浆PRL水平呈正相关(P均0.001)。结论:AAP中氨磺必利较易导致ED,利培酮次之;且氨磺必利、齐拉西酮及利培酮可能导致血浆PRL水平增高。     

精神分裂症患者多药耐药基因多态性与帕利哌酮和注射用利培酮微球临床疗效的关联研究

目的 探讨中国汉族精神分裂症患者多药耐药基因(multidrug resistance gene 1,MDR1)多态性与帕利哌酮和注射用利培酮微球治疗精神分裂症的临床疗效的关联.方法 对入组的133例精神分裂症患者分别给予帕利哌酮或注射用利培酮微球治疗12周;以阳性与阴性症状量表(PANSS)作为主要疗效评价工具,以治疗结束时临床总体印象-严重程度量表(CGI-S)及人际和社交能力量表(PSP)作为次要疗效评价工具;每2周进行PANSS评定;应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法检测受试者多药耐药基因5个多态性位点的基因型,应用卡方检验和方差分析法分析各基因型与临床疗效的关联性.结果 MDR1基因多态性与主要疗效指标PANSS减分率及有效率的关联分析中未发现差异有统计学意义(P＞0.05);非参数检验分析显示:位点rs1045642 CC基因型携带者在阴性症状条目抽象思维障碍(Z=-2.62,P=0.009)及阳性症状条目夸大(Z=-2.84,P=0.005)有较好疗效;rs2032582位点GG基因型携带者在一般病理学症状条目紧张改善较差(Z=-2.50,P=0.012);rs1202169位点A等位基因携带者在一般病理学条目主动社会回避改善较好(Z=-2.09,P=0.036);rs13233308位点CC基因型携带者在一般病理学条目罪恶观念(Z=-2.09,P=0.036)和交流缺乏自发性和主动性疗效(Z=-2.73,P=0.006)改善不佳,该位点携带TT基因型的个体在紧张条目的 疗效改善较好(Z=-2.54,P=0.011).次要疗效指标分析显示,rs1045642位点C等位基因与PSP评分高度相关(Z=-2.18,P=0.029).结论 多药耐药基因多态性可能并不影响中国汉族精神分裂症患者帕利哌酮和注射用利培酮微球的临床疗效,但与妄想、社交回避的改善可能相关.     

帕利哌酮与利培酮对精神分裂症首次发病患者血清催乳素水平及体质量影响的对照研究

目的：探讨帕利哌酮与利培酮对精神分裂症首次发病患者血清催乳素水平（ PRL）及体质量的影响。方法：130例首发精神分裂症患者随机分成帕利哌酮组66例（实际完成31例）和利培酮组64例（实际完成42例）,分别给予帕利哌酮和利培酮治疗,观察12周。采用阳性与阴性症状量表（ PAN-SS）在治疗前后进行测评;同时检测血清PRL及体质量,比较治疗前后的变化。结果：两组PANSS总分治疗后各周期均显著下降（P均<0.01）,而血清PRL和体质量均较治疗前明显增加（P<0.05）;两组间比较,差异无统计学意义。结论：帕利哌酮与利培酮治疗精神分裂症首次发病患者疗效相当,但两药均可致血清PRL及体质量增高。     

阿立哌唑与利培酮对血清催乳素水平的影响

目的:比较阿立哌唑与利培酮对精神分裂症患者血清催乳素(PRL)的影响及其与临床疗效的关系。方法:选取70例精神分裂症患者,随机分为阿立哌唑组36例,利培酮组34例,分别给予阿立哌唑和利培酮治疗8周,在治疗前及治疗1、2、4、6、8周末采用阳性与阴性症状量表(PANSS)对两组进行评定。并于治疗前、中、后采用放射免疫法测查PRL水平。结果:两组PANSS减分率分别为阿立哌唑组(44.9±15.0)%、利培酮组(51.3±14.3)%,临床有效率分别为89.7%、92.1%,治疗前后阿立哌唑组PRL水平比较差异无显著性(P>0.05),利培酮组PRL明显增高(P<0.05)。阿立哌唑组治疗前后PRL水平的差值与PANSS减分率经相关分析差异有显著性(r=0.50,P<0.05),而利培酮组差异则无显著性(r=0.20,P>0.05)。出现月经紊乱或泌乳阿立哌唑组(1/14,7.1%)较利培酮组(7/18,38.9%)明显为少(χ2=4.23,P<0.05)。结论:2药对精神分裂症均有较好疗效,阿立哌唑与利培酮对PRL影响不同,与疗效关系不明显。     

帕利哌酮与利培酮治疗老年精神分裂症的对照研究

目的比较帕利哌酮缓释片与利培酮治疗老年精神分裂症的效果和安全性,为老年精神分裂症的药物治疗提供参考。方法于2014年3月-2015年12月在成都市第四人民医院就诊者中筛选126例符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准的、年龄≥60岁的老年精神分裂症患者,按计算机随机法分为帕利哌酮组和利培酮组各63例,分别给予帕利哌酮缓释片和利培酮治疗,两组疗程均为180天。于基线期及治疗第1、2、4、8、12周末、180天时采用阳性和阴性症状量表(PANSS)、副反应量表(TESS)评定疗效和不良反应,并进行心电图和肝功监测。结果共107例完成研究,帕利哌酮组54例,利培酮组53例。分别从治疗第1、2周末开始,帕利哌酮组和利培酮组各治疗时点PANSS总评分与基线期比较,差异均有统计学意义(P均0.05),两组各治疗时点PANSS总评分比较差异均有统计学意义(P0.05或0.01);治疗第180天,帕利哌酮组痊愈率高于利培酮组,差异有统计学意义(79.63%vs.62.27%,P0.05)。整个治疗期间,帕利哌酮组锥体外系副反应(EPS)发生率低于利培酮组,差异有统计学意义(9.26%vs.24.53%,P0.05)。结论帕利哌酮与利培酮均能改善老年精神分裂症患者的精神症状,但帕利哌酮起效更快,疗效更佳,安全性更好。     

帕利哌酮缓释片治疗急性精神分裂症的疗效及安全性分析

目的探讨帕利哌酮缓释片治疗急性精神分裂症的临床疗效及安全性。方法选取我院2015-07-2016-05诊治的急性精神分裂症患者74例为研究对象,并遵照随机抽签方式分组,治疗组(n=37)应用帕利哌酮缓释片,对照组(n=37)口服利培酮片,对比2组临床疗效及不良反应发生率。结果 (1)治疗组治疗总有效率为97.3%,高于对照组的78.4%(P0.05);(2)治疗组不良反应事件发生率为10.8%,低于对照组的46.0%(P0.01);(3)治疗组治疗后PANSS总分是(44.1±3.5)分,低于对照组的(67.7±5.6)分(P0.01)。结论帕利哌酮缓释片治疗急性精神分裂症的临床疗效显著,安全性较高,可作为急性精神分裂症患者首选治疗药物。     

帕利哌酮缓释片治疗精神分裂症疗效及社会功能研究

帕利哌酮是非典型抗精神病药利培酮的活性代谢产物9-羟利培酮,为苯并异噁唑的衍生物,主要通过阻断5-羟色胺2A(5-HT 2A)受体和多巴胺D2(DA2)受体发挥抗精神病的作用.笔者对帕利哌酮缓释片的疗效、安全性及社会功能进行了研究,现报道如下.     

细胞色素P4502D6及多巴胺D2受体基因多态性与利培酮疗效的关联

目的 探讨细胞色素P450 2D6(cytochromes P450 2D6,CYP2D6)基因多态性、多巴胺D2受体(dopamine D2 receptor,DRD2)基因多态性与利培酮疗效的相关性.方法 对199例首发精神分裂症患者给予利培酮治疗8周,治疗前后采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评定疗效,同时收集198例正常对照进行病例-对照分析.采用聚合酶链反应序列特异性引物扩增技术检测CYP2D6/C188T、DRD2 TaqIA基因型,分析二者与利培酮临床效应的相关性.结果 病例组和对照组CYP2D6/C 188T的基因型和等位基因频率相比,差异有统计学意义(CC:40.7％ vs.21.2％,CT:25.6％ vs.45.5％,TT:33.7％vs.33.3％,P＜0.05;C:53.5％ vs.43.9％,T:46.5％ vs.56.1％,P＜0.05),病例组和对照组DRD2 TaqIA的基因型和等位基因频率相比,差异有统计学意义(A1A1:29.1％ vs.35.9％,A1A2:37.7％ vs.47.5％,A2A2:33.2％ vs.16.6％,P＜0.05; A1:48.0％ vs.59.6％,A2:52.0％ vs.40.4％,P＜0.05);CYP2D6/C 188T与DRD2TaqIA的交互作用对PANSS减分率的影响没有统计学意义(F=0.735,P＞0.05);CYP2D6/C188T,DRD2TaqIA与性别的交互作用对PANSS减分率的影响具有统计学意义(F=3.214,P＜0.05).结论 CYP2D6基因C188T多态性和DRD2基因TaqIA多态性不是影响精神分裂症患者利培酮临床疗效的易感因素,但是在协变量性别的作用下,上述基因多态性的交互作用可能影响利培酮的疗效.     

多巴胺D2、D3受体基因多态性与汉族人精神分裂症相关研究

目的探索多巴胺D2受体(Dopamine D2receptor,DRD2)基因第8外显子Taq I A位点多态和多巴胺D3受体(Dopamine D3receptor,DRD3)基因第5内含子Msp I位点多态与汉族人群精神分裂症是否关联及其在不同性别是否存有差异。方法使用聚合酶链反应-限制性片段长度多态性(Polymerase chain reaction-re-striction fragment length polymorphism,PCR-RFLP)及DNA测序技术,对317例精神分裂症患者及310名对照DRD2Taq I A基因多态性和DRD3Msp I位点基因多态性进行检测。结果患者组与对照组间DRD2 Taq I A位点等位基因分布差异显著(P<0.01)、两两基因型对比(A1/A2与A1/A1相比:P<0.05;A2/A2与A1/A1相比:P<0.01)及两基因型联合对比(A1/A2+A2/A2与A1/A1:P<0.01)组间差异也显著。性别分层研究DRD2Taq I A位点女性组间差异显著(P<0.01),男性组间差异无意义(P>0.05)。DRD3Msp I位点的基因型频率、等位基因分布及性别分层分析等所有数据均显示患者组与对照组之间差异无统计学意义(P>0.05)。风险因子趋势检验结果DRD2Taq I A位点等位基因A2:P<0.01;DRD3Msp I位点等位基因2:P>0.05。结论所得数据支持DRD2Taq I A位点等位基因A2可能为精神分裂发生的风险因子,特别对女性而言。数据分析不支持DRD3Msp I位点基因与精神分裂发生有关。此结果需更进一步研究证实。     

Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

BACKGROUND: The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. METHODS: Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. RESULTS: Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p < .0001). Prolactin levels were also significantly increased at 6 months (32.4 +/- 17.8 ng/ml; N = 43, p < .0001) and at 22 months (N = 30, 25.3 +/- 15.6 ng/ml, p < .0001). Prolactin levels were not associated with adverse effects and DRD2 alleles (Taq1A, -141C Ins/Del, C957T) did not significantly influence baseline levels or risperidone-induced increases in prolactin. CONCLUSIONS: Risperidone treatment was associated with two- to four-fold mean increases in serum prolactin in children with autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.     

多巴胺D3受体基因Ser9Gly多态性与阿立哌唑及利培酮治疗效应的关联研究

目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周后分别评测阳性与阴性症状量表(positive and negativesymptom scale,PANSS)。采用放射免疫法检测血浆催乳素水平,DNA测序技术检测DRD3基因Ser9Gly多态性,分析DRD3基因Ser9Gly多态性与两药疗效及血浆催乳素变化的关联。结果治疗8周后,两组PANSS减分率的差异无统计学意义[(59.79±23.48)vs.(63.30±22.66),P>0.05],但利培酮组血浆催乳素的变化值高于阿立哌唑组[(26.92±9.48)vs.(-25.25±8.07),P<0.05]。利培酮组中C等位基因携带者的血浆催乳素的增加明显高于未携带者[(52.48±27.01)ng/mL vs(36.07±17.46),P<0.05];而阿立哌唑组中未见此差异[(-23.27±8.36)vs.TT(-26.05±8.11),P>0.05]。两组8周后PANSS减分率(%)与DRD3基因Ser9Gly的差异均无统计学意义:阿立哌唑组[CC+CT(57.83±19.94)vs.TT(56.84±18.46),P>0.05];利培酮组[CC+CT(53.94±21.08)vs.TT(60.38±19.37),P>0.05]。结论阿立哌唑治疗女性首发精神分裂症疗效与利培酮相当,但引起血浆催乳素水平变化的幅度较小;利培酮引起血浆催乳素水平增加可能与DRD3基因Ser9Gly多态性有关联。     

Gender difference in the interaction of smoking and monoamine oxidase B intron 13 genotype in Parkinson's disease

We tested for gender-specific interactions between smoking and genetic polymorphisms of monoamine oxidase B (MAO-B) intron 13 (G or A allele), monoamine oxidase A (MAO-A) EcoRV (Yor N allele), and dopamine D2 recepor (DRD2) Taq1B (B1 or B2 allele) in a case-control study of 186 incident idiopathic Parkinson's disease (PD) cases and 296 age- and gender-matched controls. The odds ratios (ORs) for PD risk for ever smokers versus never smokers were 0.27 (95% CI: 0.13-0.58) for men of genotype G, and 1.26 (0.60-2.63) for men of genotype A (interaction chi2 = 8.14, P = 0.004). In contrast, for women, the OR for ever smokers versus never smokers were 0.62 (95% CI: 0.25-1.34) and 0.64 (95% CI: 0.18-2.21) for women of genotype GG/GA and AA, respectively (interaction chi2 = 0.001, P = 0.975). No interactions were detected between smoking and either MAO-A EcoRV or DRD2 Taq1B genotypes. These results suggest that a strong gender difference exists with respect to the modifying effect of MAO-B genotype on the smoking association with PD.     

Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome

The pathophysiology of Tourette syndrome may involve the dopamine system. Dysfunction of the dopamine receptor D2 gene leads to many neuropsychiatric disorders. The objective of this study is to test the hypothesis that the dopamine receptor D2 gene may play a role in Tourette syndrome. A total of 151 children with Tourette syndrome and 183 normal control subjects were included in the study. Polymerase chain reaction was used to identify the Taq I DRD2 and DRD2 (H313H) polymorphisms of the dopamine receptor D2 gene. The genotype proportions of Taq I DRD2 and DRD2 (H313H) polymorphisms in the two groups were significantly different (P < 0.01 for both). The odds ratio for developing Tourette syndrome in individuals with the Taq I DRD2 A1 homozygote was 2.253 (95% confidence interval, 1.124-4.517) compared with individuals with the Taq I DRD2 A2 homozygote. The odds ratio for developing Tourette syndrome in individuals with the DRD2 (H313H) C homozygote was 2.96 (95% confidence interval, 1.398-6.269) compared with individuals with DRD2 (H313H) T homozygote. This study has demonstrated an association between the dopamine receptor D2 gene and Tourette syndrome. These data suggest that the dopamine receptor D2 gene or a closely linked gene might be one of the susceptibility factors for Tourette syndrome.     

Association between Taq1 a dopamine D2 receptor polymorphism and psychopathology of schizophrenia in Japanese patients

1. Previous reports showed that the A1 allele of Taq1 A dopamine D2 receptor polymorphism was associated with lowered density and diminished function of dopamine D2 receptor. In this study, association between Taq1 A dopamine D2 receptor polymorphism and psychopathology of schizophrenia was investigated. 2. The subjects were 61 acutely exacerbated schizophrenic patients who were all Japanese descent and had received no medication for at least one month before this study. Pretreatment psychotic symptoms were assessed by the Brief Psychiatric Rating Scale (BPRS). The Taq1 A genotypes, the A1 and A2 alleles, were determined by polymerase chain reaction method. 3. The patients were divided into three genotype groups; i.e., the patients with A1/A1 allele (n=6), those with A1/A2 allele (n=32) and those with A2/A2 allele (n=23). 4. There was no significant difference in total BPRS, subgrouped symptoms (positive, negative, anxiety-depression, excitement and cognitive symptoms) or any scores of BPRS items among the three Taq1 A genotype groups. 5. The present study suggests that Taq1 A dopamine D2 receptor polymorphism does not play an important role in psychopathological symptoms of schizophrenia.     

Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients

Hyperprolactinemia is an inevitable consequence of treatment with antipsychotic agents to some extent because prolactin response to antipsychotics is related to dopamine blockade. Recent studies have suggested that polymorphisms of the dopamine receptors are associated with therapeutic response to antipsychotics. Thus, we studied the effects of major polymorphisms of dopamine-related genes on plasma concentration of prolactin. Subjects were 174 schizophrenic patients (68 males, 106 females) receiving 3 mg twice daily of risperidone for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. Five dopamine-related polymorphisms (Taq1A, -141C ins/del for DRD2, Ser9Gly for DRD3, 48 bp VNTR for DRD4, Val158Met for COMT) were identified. The mean (+/-SD) plasma concentration of prolactin in females was significantly higher than males (54.3+/-27.2 ng/ml versus 126.8+/-70.2 ng/ml, p<0.001). No dopamine-related polymorphisms differed the plasma concentration of prolactin in males or females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized partial correlation coefficients (beta)=0.551, p<0.001) and negatively with age (standardized beta=-0.202, p<0.01). No correlations were found between prolactin concentration and dopamine-related polymorphisms. These findings suggest that plasma prolactin concentrations in females are much higher than in males but the dopamine-related variants are not predominantly associated with plasma concentration of prolactin.     

Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting

RATIONALE: Many patients with psychotic symptoms respond poorly to treatment. Factors possibly affecting treatment response include the presence of polymorphisms in genes coding for various receptor populations, drug-metabolizing enzymes or transport proteins. OBJECTIVES: To investigate whether genetic polymorphisms could be indicators of treatment response to antipsychotic drugs. The genes of interest were the dopamine D2 receptor gene (DRD2), the serotonin 2A and 2C receptor genes (HTR2A and HTR2C), the P-glycoprotein gene (ABCB1 or MDR1) and the drug-metabolizing cytochrome P450 2D6 gene (CYP2D6). MATERIAL AND METHODS: Data for this naturalistic, cross-sectional study of patients requiring antipsychotic drugs and attending the Psychosis Outpatient Care clinic in J?nk?ping, Sweden were obtained from patient interviews, blood samples and information from patient files. Blood samples were genotyped for DRD2 Taq1 A, Ins/Del and Ser311Cys, HTR2A T102C, HTR2C Cys23Ser, ABCB1 1236C>T, 2677G>T/A, 3435C>T and genetic variants of CYP2D6. The patients (n=116) were grouped according to the CANSEPT method regarding significant social and clinical needs and significant side effects. RESULTS: Patients on olanzapine homozygous for ABCB1 3435T, had more significant social and clinical needs than others. Patients with one or two DRD2 Taq1 A1 alleles had a greater risk of significant side effects, particularly if they were male, Caucasian, had a schizophrenic or delusional disorder or were taking strong dopamine D2-receptor antagonistic drugs. CONCLUSION: If these results are confirmed, patients carrying the DRD2 Taq1 A1 allele would benefit from using drugs without strong dopamine D2 receptor antagonistic properties.     

多巴胺D3受体基因多态性与精神分裂症亚型及利培酮疗效相关性分析

目的探讨多巴胺D3受体(dopamine D3 receptor,DRD3)基因第一外显子丝氨酸9甘氨酸(Ser9Gly)多态性与精神分裂症临床亚型、药物疗效的关联.方法 241 例汉族首发精神分裂症患者,采用限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术测定基因型.分析判断基因多态性与精神分裂症的临床亚型、药物疗效的关联. 结果精神分裂症各亚型Ser9Gly等位基因分布存在显著性差异(p <0.05).利培酮疗效不同的患者间Ser9Gly等位基因多态性均无显著性差异. 结论 DRD3受体基因第一外显子Ser9Gly多态性可能与精神分裂症亚型相关,而与患者对药物的反应不相关.     

Differential effects of 5-HTTLPR and DRD2/ANKK1 polymorphisms on electrocortical measures of error and feedback processing in children

ObjectiveApplying a probabilistic learning task we examined the influence of functional polymorphisms of the serotonin transporter gene (5-HTTLPR) and the D2 dopamine receptor gene (DRD2/ANKK1) on error and feedback processing by measuring electrocortical event-related potentials (ERPs) in 10- to 12-year-old children.MethodsThree pairwise group comparisons were conducted on four distinguishable ERP components, two of which were response-related, the other two feedback-related.ResultsOur ERP data revealed that children carrying the short (S) variant of the 5-HTTLPR gene process their errors more intensively while exhibiting less habituation to negative feedback with task progression compared to children who are homozygous for the 5-HTTLPR long (L) variant. Children possessing the Taq1 A variant of the DRD2 gene showed greater sensitivity to negative feedback and, as opposed to Taq1 A non-carriers, a diminishing sensitivity to positive feedback with task progression. Regarding error processing, children possessing both the S variant of the 5-HTTLPR and the Taq1 A allele of the DRD2 gene showed a picture quite similar to that of the 5-HTTLPR S carriers and regarding feedback processing quite similar to that of the DRD2 Taq1 A carriers.ConclusionsOur findings support the hypotheses that the 5-HTTLPR S allele may predispose to (performance) anxiety, while DRD2 Taq1 A allele may predispose to the reward deficiency syndrome.SignificanceThe results may further enhance our understanding of known associations between these polymorphisms and psychopathology.