5-HT_（2C）受体基因多态性与首发精神分裂症患者抗精神病药物疗效的关联分析
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摘要
目的:
探讨首发精神分裂症患者的5-HT_(2C)受体基因-759C/T、-697G/C多态性与抗精神病药物治疗反应的关系,试图深化药物作用机制的研究,为新药开发、个体化用药及疾病发病机理的研究提供有益的证据。
方法:
以自编量表调查179例首发精神分裂症患者的一般临床资料。氯氮平或利培酮治疗8周,以阳性与阴性症状量表(PANSS)评定患者的症状严重程度,并根据量表的减分率将患者分为有效和无效两组(≥50%为有效,＜50%为无效),以聚合酶链式反应(PCR)扩增及限制性片段长度多态性(RFLP)技术,检测5-HT_(2C)受体基因-759C/T及-697G/C多态性的基因型和等位基因频率,将所得资料进行x~2检验和t检验。
结果:
1.5-HT_(2C)受体基因-759C/T多态性野生基因型(C/C)与突变基因型(C/T、T/T)和等位基因C、T的频率在利培酮总疗效有效组和无效组之间有显著性差异(女性患者),在利培酮改善阴性症状有效组和无效组之间各基因型频率有显著性差异,其等位基因频率无显著性差异。
2.5-HT_(2C)受体基因-697G/C多态性野生基因(C/C)型与突变基因型(C/G、G/G)基因型的频率在利培酮总疗效有效组和无效组之间无显著性差异,其等位基因频率在这两组间有显著差异(女性患者),在改善阴性症状有效组和无效组之间各基因型和等位基因频率均无显著性差异。
3.5-HT_(2C)受体基因-759C/T多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异,在氯氮平改善阴性症状有效组和无效组之间各基因型频率有显著性差异(女性患者),其等位基因频率无显著性差异。
4.5-HT_(2C)受体基因-697G/C多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异;在氯氮平改善阴性症状有效组和无效组之间各基因型频率无显著性差异,其等位基因频率有显著性差异。
5.5-HT_(2C)受体基因-759C/T多态性、-697G/C多态性的基因型和等位基因频率在利培酮和氯氮平改善阳性症状方面,有效组和无效组之间无显著性差异。
6.在抗精神病药物治疗总疗效、阳性及阴性症状改善有效组和无效组之间性别以及家族史无显著性差异。
结论:
1.5-HT_(2C)受体基因-759C/T及-697G/C多态性可能与非典型抗精神病药治疗首发精神分裂症的临床疗效有关,C/C基因型和等位基因C可能是总体疗效好和阴性症状疗效好的预测因子。
2.性别以及家族史可能与非典型抗精神病药物疗效无关。
Objective:
To investigate the association of the 5-HT_(2C)receptor gene-759C/T and-697C/G polymorphism with therapeutic response to antipsychotics in first-episode schizophrenic patients,attempt to broaden the field of medicine research and provide beneficial evidence for the exploration of novel antipsychotics,individualized therapy and etiopathogenesis of schizophrenia.
Methods:
179 first-episode schizophrenic patients were investigated with the self-compiled inventories and had been treated by risperidone and clozapine for 8 weeks.The severity of symptoms and the therapeutic responses to risperidone and clozapine were evaluaded by the positive and negative symptom scale(PANSS).The patients were divided into two groups according to the reductive rate of score of PANSS≥50%and＜50%respectively.The genotypes and allele frequencies of 5-HT_(2C) receptor genes were assayed by polymerase chain reaction(PCR) amplification and Restriction Fragment Length Polymorphism(RFLP) technique.The data analysis used with x~2 test and t test.
Results:
1.The frequencies of C/C genotype of the 5-HT_(2C)receptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between response and non-response to risperidone group in total clinical efficacy(female gender).There were significant difference of C/C,T/T,T/C genotypes frequencies between response and non-response to negative symptom with risperidone therapy.And no significant difference of T,C allele frequencies was found between the two groups.
2.The C/C genotype frequency of the 5-HT_(2C)receptor gene -697G/C polymorphism was not significantly different from C/G genotype and G/G genotype between response and non-response to risperidone group in total clinical efficacy.There was significant difference of G,C allele frequencies between the two groups(female gender).No significant difference of C/C,C/G,G/G genotypes and G,C allele frequencies was found between response and non-response to negative symptom with risperidone therapy.
3.No significant difference of C/C,C/T,T/Tgenotypes and T,C allele frequencies of the 5-HT_(2C)receptor gene -759C/T polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.The frequencies of C/C genotype of the 5-HT_(2C)receptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between negative symptom response to clozapine group and negative symptom non-response to clozapine group(female gender).No significant difference of T,C allele frequencies was found between the two groups.
4.No significant difference of C/C,C/G,G/Ggenotypes and G,C allele frequencies of the 5-HT_(2C)receptor gene -697G/C polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.There was significant difference of G,C allele frequencies between negative symptom response to clozapine group and negative symptom non-response to clozapine group.No significant difference of C/C,G/G genotypes frequencies was found between the two groups.
5.Genotypes and allele frequencies of 5-HT_(2C)receptor gene -759C/T and -697G/C polymorphism were not significantly different between response and non-response in positive symptom group.
6.We did not find significant difference between response group and non-response group in Gender and family history.
Conclusions:
1.5-HT_(2C)receptor gene -759C/T and -697G/C polymorphism may associate with clinical response to antipsychotics on first-episode schizophrenia.C/C genotype and C allele is likely to be a predictive factor to the improvement of total therapeutic effect and negative symptom with treatment of antipsychotics
2.Gender and family history may be not associated with therapeutic effect to antipsychotics
探讨首发精神分裂症患者的5-HT_(2C)受体基因-759C/T、-697G/C多态性与抗精神病药物治疗反应的关系,试图深化药物作用机制的研究,为新药开发、个体化用药及疾病发病机理的研究提供有益的证据。
方法:
以自编量表调查179例首发精神分裂症患者的一般临床资料。氯氮平或利培酮治疗8周,以阳性与阴性症状量表(PANSS)评定患者的症状严重程度,并根据量表的减分率将患者分为有效和无效两组(≥50%为有效,＜50%为无效),以聚合酶链式反应(PCR)扩增及限制性片段长度多态性(RFLP)技术,检测5-HT_(2C)受体基因-759C/T及-697G/C多态性的基因型和等位基因频率,将所得资料进行x~2检验和t检验。
结果:
1.5-HT_(2C)受体基因-759C/T多态性野生基因型(C/C)与突变基因型(C/T、T/T)和等位基因C、T的频率在利培酮总疗效有效组和无效组之间有显著性差异(女性患者),在利培酮改善阴性症状有效组和无效组之间各基因型频率有显著性差异,其等位基因频率无显著性差异。
2.5-HT_(2C)受体基因-697G/C多态性野生基因(C/C)型与突变基因型(C/G、G/G)基因型的频率在利培酮总疗效有效组和无效组之间无显著性差异,其等位基因频率在这两组间有显著差异(女性患者),在改善阴性症状有效组和无效组之间各基因型和等位基因频率均无显著性差异。
3.5-HT_(2C)受体基因-759C/T多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异,在氯氮平改善阴性症状有效组和无效组之间各基因型频率有显著性差异(女性患者),其等位基因频率无显著性差异。
4.5-HT_(2C)受体基因-697G/C多态性各基因型和等位基因的频率在氯氮平总疗效有效组和无效组之间无显著性差异;在氯氮平改善阴性症状有效组和无效组之间各基因型频率无显著性差异,其等位基因频率有显著性差异。
5.5-HT_(2C)受体基因-759C/T多态性、-697G/C多态性的基因型和等位基因频率在利培酮和氯氮平改善阳性症状方面,有效组和无效组之间无显著性差异。
6.在抗精神病药物治疗总疗效、阳性及阴性症状改善有效组和无效组之间性别以及家族史无显著性差异。
结论:
1.5-HT_(2C)受体基因-759C/T及-697G/C多态性可能与非典型抗精神病药治疗首发精神分裂症的临床疗效有关,C/C基因型和等位基因C可能是总体疗效好和阴性症状疗效好的预测因子。
2.性别以及家族史可能与非典型抗精神病药物疗效无关。
Objective:
To investigate the association of the 5-HT_(2C)receptor gene-759C/T and-697C/G polymorphism with therapeutic response to antipsychotics in first-episode schizophrenic patients,attempt to broaden the field of medicine research and provide beneficial evidence for the exploration of novel antipsychotics,individualized therapy and etiopathogenesis of schizophrenia.
Methods:
179 first-episode schizophrenic patients were investigated with the self-compiled inventories and had been treated by risperidone and clozapine for 8 weeks.The severity of symptoms and the therapeutic responses to risperidone and clozapine were evaluaded by the positive and negative symptom scale(PANSS).The patients were divided into two groups according to the reductive rate of score of PANSS≥50%and＜50%respectively.The genotypes and allele frequencies of 5-HT_(2C) receptor genes were assayed by polymerase chain reaction(PCR) amplification and Restriction Fragment Length Polymorphism(RFLP) technique.The data analysis used with x~2 test and t test.
Results:
1.The frequencies of C/C genotype of the 5-HT_(2C)receptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between response and non-response to risperidone group in total clinical efficacy(female gender).There were significant difference of C/C,T/T,T/C genotypes frequencies between response and non-response to negative symptom with risperidone therapy.And no significant difference of T,C allele frequencies was found between the two groups.
2.The C/C genotype frequency of the 5-HT_(2C)receptor gene -697G/C polymorphism was not significantly different from C/G genotype and G/G genotype between response and non-response to risperidone group in total clinical efficacy.There was significant difference of G,C allele frequencies between the two groups(female gender).No significant difference of C/C,C/G,G/G genotypes and G,C allele frequencies was found between response and non-response to negative symptom with risperidone therapy.
3.No significant difference of C/C,C/T,T/Tgenotypes and T,C allele frequencies of the 5-HT_(2C)receptor gene -759C/T polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.The frequencies of C/C genotype of the 5-HT_(2C)receptor gene -759C/T polymorphism was significant difference with C/T genotype and T/T genotype between negative symptom response to clozapine group and negative symptom non-response to clozapine group(female gender).No significant difference of T,C allele frequencies was found between the two groups.
4.No significant difference of C/C,C/G,G/Ggenotypes and G,C allele frequencies of the 5-HT_(2C)receptor gene -697G/C polymorphism was found between response to clozapine group and non-response to clozapine group of total clinical efficacy.There was significant difference of G,C allele frequencies between negative symptom response to clozapine group and negative symptom non-response to clozapine group.No significant difference of C/C,G/G genotypes frequencies was found between the two groups.
5.Genotypes and allele frequencies of 5-HT_(2C)receptor gene -759C/T and -697G/C polymorphism were not significantly different between response and non-response in positive symptom group.
6.We did not find significant difference between response group and non-response group in Gender and family history.
Conclusions:
1.5-HT_(2C)receptor gene -759C/T and -697G/C polymorphism may associate with clinical response to antipsychotics on first-episode schizophrenia.C/C genotype and C allele is likely to be a predictive factor to the improvement of total therapeutic effect and negative symptom with treatment of antipsychotics
2.Gender and family history may be not associated with therapeutic effect to antipsychotics
引文
[1】张维熙,沈渔邨,李淑然等.中国七个地区精神疾病流行病学调查[J].中华精神科杂志,1998,31(2):69-71
[2]Cardno AG,Gottesman Ⅱ.Twin studies of schizophrenia:from and arrow concordances to star wars Mx and functional genomics[J].Am J Med Genet,2002,97:12-17
[3]徐维衡.医学遗传学基础.北京:北京医科大学协和医科大学联合出版社,1993
[4]Gottesman Ⅱ Schizophemia Genesis:The Origins of Madness.New York,N Y WH.Freeman& Company,1991
[5】沈渔邮 精神病学第四版.北京:人民卫生出版社.1994,P.576
[6]Wyatt,R.J,He nter,L;Le ary,M C.;andTaylor,E.An economic evaluation of schizophernia--1991.Social Psychiatry and Psychiatric Epidemiology 1995;30:196-205
【7]杨珺,王世岭,王芮.遗传药理学在临床安全用药中的作用.药物不良反应杂志,2003,5:292-296
[8]蔡卫民.遗传药理学在个体化用药中的应用前景.中国药学杂志,2003,38(8):572-575
[9]刘铁桥,陈晓岗,赵靖平等.抗精神病药的遗传药理学研究.中华精神科杂志,2004,37(3):190-192.
[10]Balestried,A andD.Fontanari,Acquierd and crossed tolerance to mescaline,LSD-25,an dBOL-148.Arch Gen Psychiatry,1959.1:p.27 9-82.
[11]Lieberman JA & Koreen AR Neurochemistry and neumendoctinology of schizophrenia:A selective review Schizo Bull.1993;19:371-430
[12]Breier A.Seortonin,schizophrenia and antipsychotic drug action.Schizophr Res 1995;(3):187-202
[13]Baumgarten HG,Grozdanovic Z.Psychopharmacology of central serotonergic systems.Pharmacopsychiatry.1995 Oct;28 Suppl 2:73-9.Review.
[14]Clifton PG,Kennett GAMonoamine receptors in the regulation of feeding behaviour and energy balance.CNS Neurol Disord Drug Targets.2006 Jun;5(3):293-312.Review
[15]Di Matteo V,Marisa C,Di Giulio C,et al.Role of serotonin(2C)receptors in the control of brain dopamiaergle function.Phamacolopy Biochemistry and Behavior, 2002.71(4):727.
[16] Di Matteo V, Marisa C, Di Giulio C, et al.Biochemical evidence that the atypical antipsychotic drags clozapine and risperidone block 5-HT(2) receptors in vivo. Phamacolopy Biochemistry and Behavior,2002.71(4):607..
[17] Milatovich, A., Hsieh, C.L., Bonaminio, G, Tecott, L., Julius, D., Francke, U., 1992. Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). Hum. Mol. Genet. 1,681-684.
[18] Marazziti, D., Rossi, A., Giannaccini, G, Zavaglia, K.M., Dell'Osso,L.,Lucacchini, A., Cassano, G.B., 1999. Distribution and characterizationof [3H] mesulergine binding in human brain postmortem. Eur. Neuropsychopharmacol.10,21-26.
[19] Lappalainen, J., Zhang, L., Dean, M, Oz, M., Ozaki, N., Yu, D.H.,Virkkunen, M., Weight, F., Linnoila, M., Goldman, D., 1995. Identification,expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2C receptor gene (HTR2C). Genomics 27,274-279.
[20] Sodihi MS ,Arranz MJ , Curtis D ,et al. Association between clozapine response and allelic variation in the 52HT2Creceptor gene[J ] . Neuroreport ,1995 ,7:169
[21] Masellis M , Basile U , Meltzer H Y, et al. Serotonin subtype 2 receptor gene and clinical response to clozapine in schizophrenia patient s [J Neuropsychopharmcology, 1998 ,19 :123
[22] Rietschel, M, Naber, D., Fimmers, R., Moller, H.J., Propping, P.,Nothen,M.M., 1997. Efficacy and side-effects of clozapine notassociated with variation in the 5-HT2C receptor. NeuroReport 8,1999- 2003.
[23] Arranz, M.J., Munro, J., Birkett, J., Bolonna, A., Mancama, D., Sodhi, M.,Lesch, K.P., Meyer, J.F., Sham, P., Collier, D.A., Murray, R.M., Kerwin,R.W., 2000.Pharmacogenetic prediction of clozapine response. Lancet 2355, 1615-1616.
[24] Malin Alenius ,Mia Wadelius , Marja-Liisa Dahl, et al. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting Journal of Psychiatric Research xxx (2007) xxx-xxx
[25] Hong, C.J., Lin, C.H., Yu, Y.W.Y., Yang, K.H, Tsai, S.J, 2001. Genetic variants of the serotonin system and weight change during clozapine treatment.Pharmacogenetics 11,265- 268.
[26] Yuan, X., Yamada, K., Ishiyama-Shigemoto, S., Koyama, W., Nonaka, K.,2000. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes.Diabetologia 43, 373-376.
[27] Reynolds, G.P., Zhang, Z.J., Zhang, X.B., 2002. Association of antipsychotic drug-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene. Lancet 359,2086- 2087.
[28] Miller, D.D., Ellingrod, V.L., Holman, T.L., Buckley, P.F., Arndt, S., 2004.Clozapine-induced weight gain associated with the 5HT2C receptor759C/Tpolymorphism. Am. J. Med. Genetics 133, 97-100.
[29] Templeman, L.A., Reynolds, G.P., Arranz, B., San, L., 2005.Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug- induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenetics 15, 195-200.
[30] Ryu S, Cho EY, Park T,et al. -759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment.Progress in neuro- Neuropsychopharmacology and Biological Psychiatry. 2007Apr13;31(3):673-7.
[31] Tsai, S.J., Hong, C.J., Yu, Y.W.Y., Lin, C.H, 2002. _759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain.Lancet 360,1790.
[32] Basile, V.S., Masellis, M., De Luca, V., Meltzer, H.Y., Kennedy, J.L.,2002.- 759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 360,1790- 1791.
[33] Theisen FM, Hinney A, Bromel T, et al.Lack of association between the-759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatric Genetics. 2004 Sep; 14(3):139-42.
[34] Park YM, Cho JH, Kang SG, et al. Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. Journal of Clinical Pharmacy and Therapeutics 2008 Feb;33(1):55-60.
[35] Zhang, Z.J., Zhang, X.B., Sha, W.W., Zhang, X.B., 2002. Association of a polymorphism of the promoter region of the serotonin 5-HT2C receptor gene with tardive dyskinesia in patients with schizophrenia. Mol.Psychiatry 7, 670- 671.
[36]Gunes A,Scordo MG,Jaanson P,Dahl ML.Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.Psychopharmacology(Berl).2007 Mar;190(4):479-84
[37]姚志剑,张志珺,姚辉等五羟色胺2C受体基因多态性与抗精神病药急性期治疗精神分裂症疗效关系初探 中国神经精神疾病杂志 2003 29(6)438-441
[38]Gavin P.Reynoldsa,,Lucy A.Templeman,Zhi Jun Zhang The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment Neuro-Psychopharmacology & Biological Psychiatry 29(2005)1021-1028
Milatovich,A.,Hsieh,C.L.,Bonaminio,G.,Tecott,L.,Julius,D.,Francke,U.,1992.Serotonin receptor lc gene assigned to X chromosome inhuman(band q24)and mouse(bands D-F4).Hum.Mol.Genet.1,681-684.
[39】周宏灏.遗传药理学.北京:人民军医出版社,2002.
[40]Eberle-Wang K,Mikeladze Z,Uryu K,Chesselet MF.Pattem of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats.J Comp Neurol.1997 Jul 28;384(2):233-47.
[41]Clemett DA,Punhani T,Duxon MS,Blackburn TP,Fone KC.Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS.Neuropharmacology.2000;39(1):123-32
[42]Prisco,S.,Pagannone,S.,Esposito,E.,1994.Serotonin- dopamine interactions in the ventral tegrnental area:an electrophysiological study invivo.J.Pharmacol.Exp.Ther.271,83-90.
[43]Kelland,M.D.,Chiodo,L.A.,1996.Serotonergic modulation of midbrain dopamine systems.In:Ashby,C.R.(Ed.),The modulation of dopaminergic neurotransmission by other neurotransmitters.CRC Press,NewYork,pp.87-122.
[44]Millan,M.J.,Dekeyne,A.,Gobert,A.,1998a.Serotonin(5-HT)2C receptorstonically inhibit dopamine(DA).and noradrenaline(NA),but not 5-HT,release in the frontal cortex in vivo.Neuropharmacology 37(7),953-955.
[45]Di Matteo,V.,Di Giovanni,G.,Di Mascio,M.,Esposito,E.,1999.SB242084,a selective serotonin2C receptor antagonist,increases dopaminergic transmission in the mesolimbic system.Neuropharmacology 38,1195-1205.
[46]Gobert,A.,Rivet,J.M.,Lejeune,F.,Newman-Yancredi,A.,Adhumeau- Auclair,A.,Nicolas,J.P.,Cistarelli,L.,Melon,C.,Millan,M.J.,2000.Serotonin2C receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic,but not serotonergic,pathways:a combined dialysis and electrophysiological analysis in the rat.Synapse36,205-221.
[47]Herrick-Davis K,Grinde E,Teitler M.Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.J Pharmacology Exp Therapy.2000 Oct;295(1):226-32.
[48]Bums,C.M.,Chu,H.,Rueter,S.M.,Hutchinson,L.K.,Canton,H.,Sanders-Bush,E.,Emeson,R.B.,1997.Regulation of serotonin-2Creceptor G-protein coupling by RNA editing.Nature 387,303-308.
[49]Pinals DA,Malhotra AK,Missar CD,Pickar D,Breier A.Lack of gender differences in neuroleptic response in patients with schizophrenia.Schizophrenia Research.1996 Dec 15;22(3):215-22.
[50]Labelle A,Light M,Dunbar F.Risperidone treatment of outpatients with schizophrenia:no evidence of sex differences in treatment response.Canadian Journal of Psychiatry.2001 Aug;46(6):534-41.
【51】刘铁桥.性别与精神分裂症.国外医学精神病学分册,1992,4:208.
[52]刘铁桥,杨德森,郝伟等.首发精神分裂症住院病人疗效影响因素.临床精神医学杂志,1998,8(5):264-266.
[53]Lieberman JA,Koreen AR,Chakos M,et al.Factors influencing treatment response and outcome of first-episode schizophrenia:implications for understanding the pathophysiology of schizophrenia.J Clin Psychiatry,1996,Suppl 9:5-9.
[54]Szymanski S,Lieberman JA,Alvir JM,et al.Gender differences in onset of illness,treatment response,course,and biologic indexes in first-episode schizophrenic patients.Am J Psychiatry,1995,152:698-703.
[55]Lane HY,Chang YC,Chiu CC,et al.Influences of patient-related variables on risperidone efficacy for acutely exacerbated schizophrenia:analyses with rigorous statistics.J Clin Psychopharmacol,2002,22:353- 358.
[56]Lane.HY,Lin CC,Huang CH,et al.Risperidone response and 5-HT6receptor gene variance:genetic association analysis with adjustment for nongenetic confounders.Schizophr Res,2004,67(1):63-70.
[57]Roy MA,Flarm MA,Gupta S,et al.Epidemiological and clinical correlates of familial and sporadic schizophrenia[J].Acta Psychiatr Scand,1994,89(3):324.
[58]Kendler KS,Me Guire M,Grueberg.AM and Walsh D.Cinical hetero2geneity in schizophrenia and the pattern of paychopathology in relatives: results form an epidemiologically based family study[J].Acta Psychiatr Scand,1994,89(2):294.
[1] Mackowiak M, Czyrak A, Wedzony K. The involvement of 5-HT1a serotonin receptors in the pathophysiology and pharmacotherapy of schizophrenia psychiatria 2000 Jul-Aug;34(4):607-621.
[2] Bantick RA, Deakin JF, Grasby PM.The 5-HT1A receptor in schizophrenia: apromising target for novel atypical neuroleptics?J Psychopharmacol. 2001 Mar;15(1):37-46.
[3] Haleem DJ, Khan NH .Enhancement of serotonin-1A receptor dependent responses following withdrawal of haloperidol in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):645-651.
[4] Gavin P Reynolds; Belen Arranz; Lucy A Templeman; et al: Effect of 5-HT_(1A)Receptor Gene Polymorphism on Negative and Depressive symptom Response to Rntipsychotic Trestent of Drug-Naive Psychotic Patient. The American Journal of Psychiatry; Oct 2006; 163,10; Academic Research Library
[5] Audinot V, Newman-Tancredi A,Cussac D,Millan MJ: Inverse agonist properties of antipsychotic agents at cloned,human(h) serotonin 5-HT1B) and h5-HT(lD) renceptors.Neuropsychopharmacology 2001;25:410-422.
[6] Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, et al:Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry. 2004 Feb 1;55(3):225-233.
[7] Chen-Jee Hong ,Guo-Mei Pan,Shih-Jen Tsai Association study of onset age ,attempted suicid,aggressive behavior,and schizophreniawith a serotonin 1B receptor (A-161T) Genetic polymorphism Neuropsychobiology 2004;49:1-4
[8] Ambrosio AM, Kennedy JL, Macciardi F Lack of association or linkage disequilibrium between schizophrenia and polymorphisms in the 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes: family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128(1):1-5.
[9] Cordeiro Q, Vallada H. Lack of association between the G681C polimorphism in the 5-HTlD(beta) autoreceptor gene and schizophrenia.Arq Neuropsiquiatr. 2005 Jun;63(2B):380-382.
[10]Dean B,Pavey G,Thomas D,Scarr E.Cortical scrotonin7,1D and 1F receptors:effects of schizophrenia,suicide and antipsychotic drug treatment.Schizophr Res.2006 Dec;88(1-3):265-274.
[11]Shimron-Abarbanell D,Harms H,Erdmann J,et al:Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia.Am J Med Genet.1996 Apr 9;67(2):225-228.
[12]Inayama Y,Yoneda H,Sakai T,et al:Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia.American Journal of Medical Genetic.1996 Feb 16;67(1):103-5.
[13]Saiz PA,Garcia-Portilla MP,Arango C Association study of serotonin 2A receptor(5-HT2A)and serotonin transporter(5-HTT)gene polymorphisms with schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry.2007 Apr 13;31(3):741-5.
[14]Penas-Lledo EM,Dorado P,Caceres Me,de la Rubia A,Llerena A.Association between T102C and A-1438G polymorphisms in the serotonin receptor 2A(5-HT2A)gene and schizophrenia:relevance for treatment with antipsychotic drugs.Clin Chem Lab Med.2007;45(7):835-8.
[15】罗星光,江开达,顾牛范:精神分裂症与5-HT2a受体基因T102C多态性的关联研究.中国神经精神疾病杂志,2000;26(3):156-158.
【16】李飞,江开达,钱伊萍,等.精神分裂症患者核心家系的5-羟色胺2A受体基因的传递/不平衡检验分析.中华精神科杂志,2001,34(4):201-203
[17]Arranz MJ,Munro J,Owen MJ,et al:Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine.Mol Psychiatry.1998 Jan;3(1):61-6.
[18]Masellis M,Basile V,Meltzer HY et al:Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients.Neuropsychopharmacology.1998 Aug;19(2):123-32.
[19]Gunes A,Scordo MG,Jaanson P,Dahl ML.Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.Psychopharmacology(Berl).2007Mar;190(4):479-84.
[20]Guzey C,Scordo MG,Spina E,Landsem VM,Spigset OEuropean Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms.Journal of Clinical Pharmacology Mar 2007.Vol.63,Iss.3;pg.233
[21] Lerer B, Segman RH, Tan EC, Basile VS Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int J Neuropsychopharmacol.2005 Sep;8(3):411-25.
[22] Sodihi MS ,Arranz MJ , Curtis D ,et al. Association between clozapine response and allelic variation in the 52HT2Creceptor gene[J ] . Neuroreport, 1995 ,7:169
[23] Masellis M , Basile U , Meltzer H Y, et al. Serotonin subtype 2 receptor gene and clinical response to clozapine inschizophrenia patient s [J]. Neuropsychoph-armcology,1998 ,19:123
[24] Hong, C.J., Lin, C.H., Yu, Y.W.Y., Yang, K.H., Tsai, S.J., 2001. Genetic variants of the serotonin system and weight change during clozapine treatment.Pharmacogenetics 11,265- 268.
[25] Yuan, X., Yamada, K., Ishiyama-Shigemoto, S., Koyama, W., Nonaka, K.,2000. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes.Diabetologia 43, 373-376.
[26] Reynolds, G.P., Zhang, Z.J., Zhang, X.B., 2002. Association of antipsychotic drug-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene. Lancet 359,2086- 2087.
[27] Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and Ieptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005 Apr;15(4): 195-200.
[28] RyuS, Cho EY, Park T, et al:-759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31 (3):673-7.
[29]. Niesler, Beate a; Weiss, Birgit a; Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients. Pharmacogenetics. 11(1): 21-27,February2001.
[30] Gutierrez B , Arranz MJ , Huezo2Diaz P , et al. Novel mutations in 52HT3A and 52HT3B receptor genes not associated with clozapine response [J ] . Schizophr Res,2002,58(1):93
[31]Thompson AJ,Sullivan NL,Lummis SC.Characterization of 5-HT3receptor mutations identified in schizophrenic patients.J Mol Neurosci.2006;30(3):273-81.
[32]Birket t J T,Arranz MJ,Munro J,et al.Association a2 nalysis of the 52HT5A gene in depression,psychosis and anti2 psychotic response[J]Neuroreport,2000,11(9):2017
[33】贺林,李胜,将嵩山,等.多巴胺及52羟色胺系统中精神分裂症相关基因研究[J].云南大学学报(自然科学版),2002,21:292
[34]Shinkai T,Ohmori O,Kojima H,et al.Association study of the 5-HT6receptor gene in schizophrenia.Am J Med Genet,1999,88:120-123.
[35]East SZ,Bumet PW,Kerwin RW,et al.An RT-PCR study of 5-HT6 and 5-HT7 receptor mRNAs in the hippocampal formation and prefrontal cortex in schizophrenia.Schizophr Res,2002,57:15-26.
[36]Matsumoto M,Togashi H,Mori K,et al.Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.Eur J Pharmacol,1999,383(1):39-48.
[37]Yu YW,Tsai S J,Lin CH,et al.1999.Serotonin-6 receptor variant(C267T)and clinical response to clozapine.NeuroReport,1999,10:1231-1233.
[38]Masellis M.,Basile VS,Meltzer HY,et al.Lack of association between the T→C 267 serotonin 5-HT6 receptor gene(HTR6)polymorphism and prediction of response to clozapine in schizophrenia.Schizophr.Res,2001,47:49-58.
[39]Lane HY,Lin CC,Huang CH,et al.Risperidone response and 5-HT6receptor gene variance:genetic association analysis with adjustment for nongenetic confounders.Schizophr Res,2004,67(1):63-70.
[40]Erdmann J,Nothen MM,Shimron-Abarbanell D,et al.The human serotonin 7(5-HT7)receptor gene:genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder.Mol Psychiatry.1996 Nov;1(5):392-7.
[41]Ikeda M,Iwata N,Kitajima T,et al.Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population.Neuropsychop-harmacology.2006 Apr;31(4):866-71.
[2]Cardno AG,Gottesman Ⅱ.Twin studies of schizophrenia:from and arrow concordances to star wars Mx and functional genomics[J].Am J Med Genet,2002,97:12-17
[3]徐维衡.医学遗传学基础.北京:北京医科大学协和医科大学联合出版社,1993
[4]Gottesman Ⅱ Schizophemia Genesis:The Origins of Madness.New York,N Y WH.Freeman& Company,1991
[5】沈渔邮 精神病学第四版.北京:人民卫生出版社.1994,P.576
[6]Wyatt,R.J,He nter,L;Le ary,M C.;andTaylor,E.An economic evaluation of schizophernia--1991.Social Psychiatry and Psychiatric Epidemiology 1995;30:196-205
【7]杨珺,王世岭,王芮.遗传药理学在临床安全用药中的作用.药物不良反应杂志,2003,5:292-296
[8]蔡卫民.遗传药理学在个体化用药中的应用前景.中国药学杂志,2003,38(8):572-575
[9]刘铁桥,陈晓岗,赵靖平等.抗精神病药的遗传药理学研究.中华精神科杂志,2004,37(3):190-192.
[10]Balestried,A andD.Fontanari,Acquierd and crossed tolerance to mescaline,LSD-25,an dBOL-148.Arch Gen Psychiatry,1959.1:p.27 9-82.
[11]Lieberman JA & Koreen AR Neurochemistry and neumendoctinology of schizophrenia:A selective review Schizo Bull.1993;19:371-430
[12]Breier A.Seortonin,schizophrenia and antipsychotic drug action.Schizophr Res 1995;(3):187-202
[13]Baumgarten HG,Grozdanovic Z.Psychopharmacology of central serotonergic systems.Pharmacopsychiatry.1995 Oct;28 Suppl 2:73-9.Review.
[14]Clifton PG,Kennett GAMonoamine receptors in the regulation of feeding behaviour and energy balance.CNS Neurol Disord Drug Targets.2006 Jun;5(3):293-312.Review
[15]Di Matteo V,Marisa C,Di Giulio C,et al.Role of serotonin(2C)receptors in the control of brain dopamiaergle function.Phamacolopy Biochemistry and Behavior, 2002.71(4):727.
[16] Di Matteo V, Marisa C, Di Giulio C, et al.Biochemical evidence that the atypical antipsychotic drags clozapine and risperidone block 5-HT(2) receptors in vivo. Phamacolopy Biochemistry and Behavior,2002.71(4):607..
[17] Milatovich, A., Hsieh, C.L., Bonaminio, G, Tecott, L., Julius, D., Francke, U., 1992. Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). Hum. Mol. Genet. 1,681-684.
[18] Marazziti, D., Rossi, A., Giannaccini, G, Zavaglia, K.M., Dell'Osso,L.,Lucacchini, A., Cassano, G.B., 1999. Distribution and characterizationof [3H] mesulergine binding in human brain postmortem. Eur. Neuropsychopharmacol.10,21-26.
[19] Lappalainen, J., Zhang, L., Dean, M, Oz, M., Ozaki, N., Yu, D.H.,Virkkunen, M., Weight, F., Linnoila, M., Goldman, D., 1995. Identification,expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2C receptor gene (HTR2C). Genomics 27,274-279.
[20] Sodihi MS ,Arranz MJ , Curtis D ,et al. Association between clozapine response and allelic variation in the 52HT2Creceptor gene[J ] . Neuroreport ,1995 ,7:169
[21] Masellis M , Basile U , Meltzer H Y, et al. Serotonin subtype 2 receptor gene and clinical response to clozapine in schizophrenia patient s [J Neuropsychopharmcology, 1998 ,19 :123
[22] Rietschel, M, Naber, D., Fimmers, R., Moller, H.J., Propping, P.,Nothen,M.M., 1997. Efficacy and side-effects of clozapine notassociated with variation in the 5-HT2C receptor. NeuroReport 8,1999- 2003.
[23] Arranz, M.J., Munro, J., Birkett, J., Bolonna, A., Mancama, D., Sodhi, M.,Lesch, K.P., Meyer, J.F., Sham, P., Collier, D.A., Murray, R.M., Kerwin,R.W., 2000.Pharmacogenetic prediction of clozapine response. Lancet 2355, 1615-1616.
[24] Malin Alenius ,Mia Wadelius , Marja-Liisa Dahl, et al. Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting Journal of Psychiatric Research xxx (2007) xxx-xxx
[25] Hong, C.J., Lin, C.H., Yu, Y.W.Y., Yang, K.H, Tsai, S.J, 2001. Genetic variants of the serotonin system and weight change during clozapine treatment.Pharmacogenetics 11,265- 268.
[26] Yuan, X., Yamada, K., Ishiyama-Shigemoto, S., Koyama, W., Nonaka, K.,2000. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes.Diabetologia 43, 373-376.
[27] Reynolds, G.P., Zhang, Z.J., Zhang, X.B., 2002. Association of antipsychotic drug-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene. Lancet 359,2086- 2087.
[28] Miller, D.D., Ellingrod, V.L., Holman, T.L., Buckley, P.F., Arndt, S., 2004.Clozapine-induced weight gain associated with the 5HT2C receptor759C/Tpolymorphism. Am. J. Med. Genetics 133, 97-100.
[29] Templeman, L.A., Reynolds, G.P., Arranz, B., San, L., 2005.Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug- induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenetics 15, 195-200.
[30] Ryu S, Cho EY, Park T,et al. -759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment.Progress in neuro- Neuropsychopharmacology and Biological Psychiatry. 2007Apr13;31(3):673-7.
[31] Tsai, S.J., Hong, C.J., Yu, Y.W.Y., Lin, C.H, 2002. _759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain.Lancet 360,1790.
[32] Basile, V.S., Masellis, M., De Luca, V., Meltzer, H.Y., Kennedy, J.L.,2002.- 759C/T genetic variation of 5HT(2C) receptor and clozapine-induced weight gain. Lancet 360,1790- 1791.
[33] Theisen FM, Hinney A, Bromel T, et al.Lack of association between the-759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals. Psychiatric Genetics. 2004 Sep; 14(3):139-42.
[34] Park YM, Cho JH, Kang SG, et al. Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients. Journal of Clinical Pharmacy and Therapeutics 2008 Feb;33(1):55-60.
[35] Zhang, Z.J., Zhang, X.B., Sha, W.W., Zhang, X.B., 2002. Association of a polymorphism of the promoter region of the serotonin 5-HT2C receptor gene with tardive dyskinesia in patients with schizophrenia. Mol.Psychiatry 7, 670- 671.
[36]Gunes A,Scordo MG,Jaanson P,Dahl ML.Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.Psychopharmacology(Berl).2007 Mar;190(4):479-84
[37]姚志剑,张志珺,姚辉等五羟色胺2C受体基因多态性与抗精神病药急性期治疗精神分裂症疗效关系初探 中国神经精神疾病杂志 2003 29(6)438-441
[38]Gavin P.Reynoldsa,,Lucy A.Templeman,Zhi Jun Zhang The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of antipsychotic drug treatment Neuro-Psychopharmacology & Biological Psychiatry 29(2005)1021-1028
Milatovich,A.,Hsieh,C.L.,Bonaminio,G.,Tecott,L.,Julius,D.,Francke,U.,1992.Serotonin receptor lc gene assigned to X chromosome inhuman(band q24)and mouse(bands D-F4).Hum.Mol.Genet.1,681-684.
[39】周宏灏.遗传药理学.北京:人民军医出版社,2002.
[40]Eberle-Wang K,Mikeladze Z,Uryu K,Chesselet MF.Pattem of expression of the serotonin2C receptor messenger RNA in the basal ganglia of adult rats.J Comp Neurol.1997 Jul 28;384(2):233-47.
[41]Clemett DA,Punhani T,Duxon MS,Blackburn TP,Fone KC.Immunohistochemical localisation of the 5-HT2C receptor protein in the rat CNS.Neuropharmacology.2000;39(1):123-32
[42]Prisco,S.,Pagannone,S.,Esposito,E.,1994.Serotonin- dopamine interactions in the ventral tegrnental area:an electrophysiological study invivo.J.Pharmacol.Exp.Ther.271,83-90.
[43]Kelland,M.D.,Chiodo,L.A.,1996.Serotonergic modulation of midbrain dopamine systems.In:Ashby,C.R.(Ed.),The modulation of dopaminergic neurotransmission by other neurotransmitters.CRC Press,NewYork,pp.87-122.
[44]Millan,M.J.,Dekeyne,A.,Gobert,A.,1998a.Serotonin(5-HT)2C receptorstonically inhibit dopamine(DA).and noradrenaline(NA),but not 5-HT,release in the frontal cortex in vivo.Neuropharmacology 37(7),953-955.
[45]Di Matteo,V.,Di Giovanni,G.,Di Mascio,M.,Esposito,E.,1999.SB242084,a selective serotonin2C receptor antagonist,increases dopaminergic transmission in the mesolimbic system.Neuropharmacology 38,1195-1205.
[46]Gobert,A.,Rivet,J.M.,Lejeune,F.,Newman-Yancredi,A.,Adhumeau- Auclair,A.,Nicolas,J.P.,Cistarelli,L.,Melon,C.,Millan,M.J.,2000.Serotonin2C receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic,but not serotonergic,pathways:a combined dialysis and electrophysiological analysis in the rat.Synapse36,205-221.
[47]Herrick-Davis K,Grinde E,Teitler M.Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.J Pharmacology Exp Therapy.2000 Oct;295(1):226-32.
[48]Bums,C.M.,Chu,H.,Rueter,S.M.,Hutchinson,L.K.,Canton,H.,Sanders-Bush,E.,Emeson,R.B.,1997.Regulation of serotonin-2Creceptor G-protein coupling by RNA editing.Nature 387,303-308.
[49]Pinals DA,Malhotra AK,Missar CD,Pickar D,Breier A.Lack of gender differences in neuroleptic response in patients with schizophrenia.Schizophrenia Research.1996 Dec 15;22(3):215-22.
[50]Labelle A,Light M,Dunbar F.Risperidone treatment of outpatients with schizophrenia:no evidence of sex differences in treatment response.Canadian Journal of Psychiatry.2001 Aug;46(6):534-41.
【51】刘铁桥.性别与精神分裂症.国外医学精神病学分册,1992,4:208.
[52]刘铁桥,杨德森,郝伟等.首发精神分裂症住院病人疗效影响因素.临床精神医学杂志,1998,8(5):264-266.
[53]Lieberman JA,Koreen AR,Chakos M,et al.Factors influencing treatment response and outcome of first-episode schizophrenia:implications for understanding the pathophysiology of schizophrenia.J Clin Psychiatry,1996,Suppl 9:5-9.
[54]Szymanski S,Lieberman JA,Alvir JM,et al.Gender differences in onset of illness,treatment response,course,and biologic indexes in first-episode schizophrenic patients.Am J Psychiatry,1995,152:698-703.
[55]Lane HY,Chang YC,Chiu CC,et al.Influences of patient-related variables on risperidone efficacy for acutely exacerbated schizophrenia:analyses with rigorous statistics.J Clin Psychopharmacol,2002,22:353- 358.
[56]Lane.HY,Lin CC,Huang CH,et al.Risperidone response and 5-HT6receptor gene variance:genetic association analysis with adjustment for nongenetic confounders.Schizophr Res,2004,67(1):63-70.
[57]Roy MA,Flarm MA,Gupta S,et al.Epidemiological and clinical correlates of familial and sporadic schizophrenia[J].Acta Psychiatr Scand,1994,89(3):324.
[58]Kendler KS,Me Guire M,Grueberg.AM and Walsh D.Cinical hetero2geneity in schizophrenia and the pattern of paychopathology in relatives: results form an epidemiologically based family study[J].Acta Psychiatr Scand,1994,89(2):294.
[1] Mackowiak M, Czyrak A, Wedzony K. The involvement of 5-HT1a serotonin receptors in the pathophysiology and pharmacotherapy of schizophrenia psychiatria 2000 Jul-Aug;34(4):607-621.
[2] Bantick RA, Deakin JF, Grasby PM.The 5-HT1A receptor in schizophrenia: apromising target for novel atypical neuroleptics?J Psychopharmacol. 2001 Mar;15(1):37-46.
[3] Haleem DJ, Khan NH .Enhancement of serotonin-1A receptor dependent responses following withdrawal of haloperidol in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):645-651.
[4] Gavin P Reynolds; Belen Arranz; Lucy A Templeman; et al: Effect of 5-HT_(1A)Receptor Gene Polymorphism on Negative and Depressive symptom Response to Rntipsychotic Trestent of Drug-Naive Psychotic Patient. The American Journal of Psychiatry; Oct 2006; 163,10; Academic Research Library
[5] Audinot V, Newman-Tancredi A,Cussac D,Millan MJ: Inverse agonist properties of antipsychotic agents at cloned,human(h) serotonin 5-HT1B) and h5-HT(lD) renceptors.Neuropsychopharmacology 2001;25:410-422.
[6] Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, et al:Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry. 2004 Feb 1;55(3):225-233.
[7] Chen-Jee Hong ,Guo-Mei Pan,Shih-Jen Tsai Association study of onset age ,attempted suicid,aggressive behavior,and schizophreniawith a serotonin 1B receptor (A-161T) Genetic polymorphism Neuropsychobiology 2004;49:1-4
[8] Ambrosio AM, Kennedy JL, Macciardi F Lack of association or linkage disequilibrium between schizophrenia and polymorphisms in the 5-HT1Dalpha and 5-HT1Dbeta autoreceptor genes: family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2004 Jul 1;128(1):1-5.
[9] Cordeiro Q, Vallada H. Lack of association between the G681C polimorphism in the 5-HTlD(beta) autoreceptor gene and schizophrenia.Arq Neuropsiquiatr. 2005 Jun;63(2B):380-382.
[10]Dean B,Pavey G,Thomas D,Scarr E.Cortical scrotonin7,1D and 1F receptors:effects of schizophrenia,suicide and antipsychotic drug treatment.Schizophr Res.2006 Dec;88(1-3):265-274.
[11]Shimron-Abarbanell D,Harms H,Erdmann J,et al:Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia.Am J Med Genet.1996 Apr 9;67(2):225-228.
[12]Inayama Y,Yoneda H,Sakai T,et al:Positive association between a DNA sequence variant in the serotonin 2A receptor gene and schizophrenia.American Journal of Medical Genetic.1996 Feb 16;67(1):103-5.
[13]Saiz PA,Garcia-Portilla MP,Arango C Association study of serotonin 2A receptor(5-HT2A)and serotonin transporter(5-HTT)gene polymorphisms with schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry.2007 Apr 13;31(3):741-5.
[14]Penas-Lledo EM,Dorado P,Caceres Me,de la Rubia A,Llerena A.Association between T102C and A-1438G polymorphisms in the serotonin receptor 2A(5-HT2A)gene and schizophrenia:relevance for treatment with antipsychotic drugs.Clin Chem Lab Med.2007;45(7):835-8.
[15】罗星光,江开达,顾牛范:精神分裂症与5-HT2a受体基因T102C多态性的关联研究.中国神经精神疾病杂志,2000;26(3):156-158.
【16】李飞,江开达,钱伊萍,等.精神分裂症患者核心家系的5-羟色胺2A受体基因的传递/不平衡检验分析.中华精神科杂志,2001,34(4):201-203
[17]Arranz MJ,Munro J,Owen MJ,et al:Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine.Mol Psychiatry.1998 Jan;3(1):61-6.
[18]Masellis M,Basile V,Meltzer HY et al:Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenia patients.Neuropsychopharmacology.1998 Aug;19(2):123-32.
[19]Gunes A,Scordo MG,Jaanson P,Dahl ML.Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.Psychopharmacology(Berl).2007Mar;190(4):479-84.
[20]Guzey C,Scordo MG,Spina E,Landsem VM,Spigset OEuropean Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms.Journal of Clinical Pharmacology Mar 2007.Vol.63,Iss.3;pg.233
[21] Lerer B, Segman RH, Tan EC, Basile VS Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int J Neuropsychopharmacol.2005 Sep;8(3):411-25.
[22] Sodihi MS ,Arranz MJ , Curtis D ,et al. Association between clozapine response and allelic variation in the 52HT2Creceptor gene[J ] . Neuroreport, 1995 ,7:169
[23] Masellis M , Basile U , Meltzer H Y, et al. Serotonin subtype 2 receptor gene and clinical response to clozapine inschizophrenia patient s [J]. Neuropsychoph-armcology,1998 ,19:123
[24] Hong, C.J., Lin, C.H., Yu, Y.W.Y., Yang, K.H., Tsai, S.J., 2001. Genetic variants of the serotonin system and weight change during clozapine treatment.Pharmacogenetics 11,265- 268.
[25] Yuan, X., Yamada, K., Ishiyama-Shigemoto, S., Koyama, W., Nonaka, K.,2000. Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and type II diabetes.Diabetologia 43, 373-376.
[26] Reynolds, G.P., Zhang, Z.J., Zhang, X.B., 2002. Association of antipsychotic drug-induced weight gain with a polymorphism of the promotor region of the 5-HT2C receptor gene. Lancet 359,2086- 2087.
[27] Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and Ieptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005 Apr;15(4): 195-200.
[28] RyuS, Cho EY, Park T, et al:-759 C/T polymorphism of 5-HT2C receptor gene and early phase weight gain associated with antipsychotic drug treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31 (3):673-7.
[29]. Niesler, Beate a; Weiss, Birgit a; Serotonin receptor gene HTR3A variants in schizophrenic and bipolar affective patients. Pharmacogenetics. 11(1): 21-27,February2001.
[30] Gutierrez B , Arranz MJ , Huezo2Diaz P , et al. Novel mutations in 52HT3A and 52HT3B receptor genes not associated with clozapine response [J ] . Schizophr Res,2002,58(1):93
[31]Thompson AJ,Sullivan NL,Lummis SC.Characterization of 5-HT3receptor mutations identified in schizophrenic patients.J Mol Neurosci.2006;30(3):273-81.
[32]Birket t J T,Arranz MJ,Munro J,et al.Association a2 nalysis of the 52HT5A gene in depression,psychosis and anti2 psychotic response[J]Neuroreport,2000,11(9):2017
[33】贺林,李胜,将嵩山,等.多巴胺及52羟色胺系统中精神分裂症相关基因研究[J].云南大学学报(自然科学版),2002,21:292
[34]Shinkai T,Ohmori O,Kojima H,et al.Association study of the 5-HT6receptor gene in schizophrenia.Am J Med Genet,1999,88:120-123.
[35]East SZ,Bumet PW,Kerwin RW,et al.An RT-PCR study of 5-HT6 and 5-HT7 receptor mRNAs in the hippocampal formation and prefrontal cortex in schizophrenia.Schizophr Res,2002,57:15-26.
[36]Matsumoto M,Togashi H,Mori K,et al.Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.Eur J Pharmacol,1999,383(1):39-48.
[37]Yu YW,Tsai S J,Lin CH,et al.1999.Serotonin-6 receptor variant(C267T)and clinical response to clozapine.NeuroReport,1999,10:1231-1233.
[38]Masellis M.,Basile VS,Meltzer HY,et al.Lack of association between the T→C 267 serotonin 5-HT6 receptor gene(HTR6)polymorphism and prediction of response to clozapine in schizophrenia.Schizophr.Res,2001,47:49-58.
[39]Lane HY,Lin CC,Huang CH,et al.Risperidone response and 5-HT6receptor gene variance:genetic association analysis with adjustment for nongenetic confounders.Schizophr Res,2004,67(1):63-70.
[40]Erdmann J,Nothen MM,Shimron-Abarbanell D,et al.The human serotonin 7(5-HT7)receptor gene:genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder.Mol Psychiatry.1996 Nov;1(5):392-7.
[41]Ikeda M,Iwata N,Kitajima T,et al.Positive association of the serotonin 5-HT7 receptor gene with schizophrenia in a Japanese population.Neuropsychop-harmacology.2006 Apr;31(4):866-71.