周岑;王冬思;王晓东;韩彦龙;王春涛;

• 1:牡丹江医学院生物学教研室
• 2:牡丹江医学院生物学教务处

摘要(Abstract)：

精神分裂症是以严重的精神障碍为特征的复杂疾病之一,发病机制尚未明确。研究表明该病由多个微效基因与环境因素共同作用导致,遗传因素发挥更至关重要的作用。DTNBP1基因作为精神分裂症的易感基因之一,对谷氨酸、多巴胺等神经递质具有调控作用,与神经递质假说密切相关。目前,国内外已广泛研究DTNBP1基因单核苷酸多态性与精神分裂症易感性及其临床症状之间的关联性,本文主要就已有研究进展做一综述。

关键词(KeyWords)： 精神分裂症;DTNBP1基因;神经递质假说;单核苷酸多态性;相关性

Abstract:

Keywords:

基金项目(Foundation): 牡丹江医学院研究生创新科研项目(编号：2019YJCSX-14MY);; 黑龙江省大学生创新创业训练计划项目(编号：201910229052)

作者(Authors): 周岑;王冬思;王晓东;韩彦龙;王春涛;

参考文献(References)：

• [1]JANOUTOVáJ,JANáCKOVáP,SERY O,et al.Epidemiology and risk factors of schizophrenia[J].Neuro Endocrinol Lett,2016,37(1):1-8.
• [2]CHEN S,ZHANG Y S,LI K Q.The Advances in Research of Cognitive Function in Patients with Schizophrenia Assessment[J].Chin J Health Psychol,2017,25(03):461-467.DOI:10.13342/j.cnki.cjhp.2017.03.039.
• [3]MULLIN A P,SADANANDAPPA M K,MA W,et al.Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity[J].J Neurosci,2015,35(1):325-338.DOI:10.1523/JNEUROSCI.3542-14.2015.
• [4]YUAN Q,YANG F,XIAO Y,et al.Regulation of BrainDerived Neurotrophic Factor Exocytosis and GammaAminobutyric Acidergic Interneuron Synapse by the Schizophrenia Susceptibility Gene Dysbindin-1[J].Biol Psychiatry,2016,80(4):312-322.DOI:10.1016/j.biopsych.2015.08.019.
• [5]NUMAKAWA T,YAGASAKI Y,ISHIMOTO T,et al.Evidence of novel neuronal functions of dysbindin,a susceptibility gene for schizophrenia[J].Hum Mol Genet,2004,13(21):2699-2708.DOI:10.1093/hmg/ddh280.
• [6]BHAT H F,MIR S S,DAR K B,et al.ABC of multifaceted dystrophin glycoprotein complex (DGC)[J].J Cell Physiol,2018,233(7):5142-5159.DOI:10.1002/jcp.25982.
• [7]STRAUB R E,JIANG Y,MACLEAN C J,et al.Genetic variation in the 6p22.3 gene DTNBP1,the human ortholog of the mouse dysbindin gene,is associated with schizophrenia[J].Am J Hum Genet,2004,13(21):2699-2708.DOI:10.1086/341750.
• [8]FUNKE B,FINN C T,PLOCIK A M,et al.Association of the DTNBP1 locus with schizophrenia in a U.S.population[J].Am J Hum Genet,2004,75(5):891-898.DOI:10.1086/425279.
• [9]ALIZADEH F,TABATABAIEFAR M A,GHADIRI M,et al.Association of P1635 and P1655 polymorphisms in dysbindin(DTNBP1)gene with schizophrenia[J].Acta Neuropsychiatr,2012,24(3):155-159.DOI:10.1111/j.1601-5215.2011.00598.x.
• [10]TOSATO S,RUGGERI M,BONETTO C,et al.Association study of dysbindin gene with clinical and outcome measures in a representative cohort of Italian schizophrenic patients[J].Am J Med Genet B Neuropsychiatr Genet,2007,144b(5):647-659.DOI:10.1002/ajmg.b.30484.
• [11]PAE C U,MANDELLI L,DE RONCHI D,et al.Dysbindin gene(DTNBP1)and schizophrenia in Korean population[J].Eur Arch Psychiatry Clin Neurosci,2009,259(3):137-142.DOI:10.1007/s00406-008-0830-y.
• [12]VOISEY J,SWAGELL C D,HUGHES I P,et al.Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia[J].Eur Psychiatry,2010,25(6):314-319.DOI:10.1016/j.eurpsy.2009.11.011.
• [13]DUAN J,MARTINEZ M,SANDERS A R,et al.DTN-BP1(Dystrobrevin binding protein 1)and schizophrenia:association evidence in the 3'end of the gene[J].Hum Hered,2007,64(2):97-106.DOI:10.1159/000101961.
• [14]KIROV G,IVANOV D,WILLIAMS N M,et al.Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in488 parent-offspring trios from Bulgaria[J].Biol Psychiatry,2004,55(10):971-975.DOI:10.1016/j.biopsych.2004.01.025.
• [15]VAN DEN OORD E J,SULLIVAN P F,JIANG Y,et al.Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families[J].Mol Psychiatry,2003,8(5):499-510.DOI:10.1038/sj.mp.4001263.
• [16]RILEY B,KUO P H,MAHER B S,et al.The dystrobrevin binding protein 1(DTNBP1)gene is associated with schizophrenia in the Irish Case Control Study of Schizophrenia(ICCSS)sample[J].Schizophr Res,2009,115(2/3):245-253.DOI:10.1016/j.schres.2009.09.008.
• [17]MORRIS D W,MCGHEE K A,SCHWAIGER S,et al.No evidence for association of the dysbindin gene[DT-NBP1]with schizophrenia in an Irish population-based study[J].Schizophr Res,2003,60(2/3):167-172.DOI:10.1016/S0920-9964(02)00527-3.
• [18]HOLLIDAY E G,HANDOKO H Y,JAMES M R,et al.Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples[J].Twin Res Hum Genet,2006,9(4):531-539.DOI:10.1375/183242706778025035.
• [19]J?NSSON E G,SAETRE P,VARES M,et al.DTNBP1,NRG1,DAOA,DAO and GRM3 polymorphisms and schizophrenia:an association study[J].Neuropsychobiology,2009,59(3):142-150.DOI:10.1159/000218076.
• [20]STROHMAIER J,FRANK J,WENDLAND J R,et al.Areappraisal of the association between Dysbindin(DTN-BP1)and schizophrenia in a large combined case-control and family-based sample of German ancestry[J].Schizophr Res,2010,118(1/3):98-105.DOI:10.1016/j.schres.2009.12.025.
• [21]JOO E J,LEE K Y,JEONG S H,et al.The dysbindin gene(DTNBP1)and schizophrenia:no support for an association in the Korean population[J].Neurosci Lett,2006,407(2):101-106.DOI:10.1016/j.neulet.2006.08.011.
• [22]YE N,SUN Y H,HU H L,et al.rs4715986 in DTNBP1is associatedwith paranoid schizophrenia in Chinese Han population[J].Basic Clin Med,2017,37(5):676-681.DOI:10.16352/j.issn.1001-6325.2017.05.016.
• [23]LI T,ZHANG F,LIU X,et al.Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations[J].Mol Psychiatry,2005,10(11):1037-1044.DOI:10.1038/sj.mp.4001718.
• [24]TANG J X,ZHOU J,FAN J B,et al.Family-based association study of DTNBP1 in 6p22.3 and schizophrenia[J].Mol Psychiatry,2003,8(8):717-718.DOI:10.1038/sj.mp.4001287.
• [25]LIU C M,LIU Y L,FANN C S,et al.No association evidence between schizophrenia and dystrobrevin-binding protein 1(DTNBP1)in Taiwanese families[J].Schizophr Res,2007,93(1/3):391-398.DOI:10.1016/j.schres.2007.02.003.
• [26]LUO X,PAN J,YAO X,et al.Effect of WeChat In tervention on Post-disch arge Medication Adherence and Treatment Effect in Patients with Schizophrenia[J].JShenyang Med Coll,2018,20(4):296-298.DOI:10.16753/j.cnki.1008-2344.2018.04.003.
• [27]徐烨.齐拉西酮与奥氮平对初治精神分裂症的疗效评价[J].中国实用神经疾病杂志,2017,20(11):72-74.DOI:10.3969/j.issn.1673-5110.2017.11.027.
• [28]UPTHEGROVE R,BROOME MR,CALDWELL K,et al.Understanding auditory verbal hallucinations:a systematic review of current evidence[J].Acta Psychiatr Scand,2016,133(5):352-367.DOI:10.1111/acps.12531.
• [29]PAE C U,DRAGO A,KIM J J,et al.DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients[J].Neurosci Lett,2008,440(2):150-154.DOI:10.1016/j.neulet.2008.05.069.
• [30]YANG Y,ZHANG L,GUO D,et al.Association of DTN-BP1 With Schizophrenia:Findings From Two Independent Samples of Han Chinese Population[J].Front Psychiatry,2020,11:446.DOI:10.3389/fpsyt.2020.00446.
• [31]CHEAH S Y,LAWFORD B R,YOUNG R M,et al.Dysbindin(DTNBP1)variants are associated with hallucinations in schizophrenia[J].Eur Psychiatry,2015,30(4):486-491.DOI:10.1016/j.eurpsy.2015.01.008.
• [32]BERGEN S E,FANOUS A H,KUO P H,et al.No association of dysbindin with symptom factors of schizophrenia in an Irish case-control sample[J].Am J Med Genet B Neuropsychiatr Genet,2010,153B(2):700-705.DOI:10.1002/ajmg.b.31029.
• [33]ZHANG S.Study on the efficacy of tolbutamide on the negative symptoms and improvement in depressive symptoms in teenaged patients with schiz-ophrenia[J].J Clin Exp Med,2016,15(17):1717-1719.DOI:10.3969/j.issn.1671-4695.2016.17.021.
• [34]张岩滨.哌罗匹隆联合艾司西酞普兰治疗阴性症状为主的精神分裂症临床观察[J].中国实用神经疾病杂志,2018,21(8):867-869.DOI:10.12083/SYSJ.2018.08.218.
• [35]杨旭宁,吕晓静,李晓红.抗精神病药物对精神分裂症患者血糖水平的影响[J].中国实用神经疾病杂志,2018,21(9):997-999.DOI:10.12083/SYSJ.2018.09.249.
• [36]DEROSSE P,FUNKE B,BURDICK K E,et al.Dysbindin genotype and negative symptoms in schizophrenia[J].Am J Psychiatry,2006,163(3):532-534.DOI:10.1176/appi.ajp.163.3.532.
• [37]FANOUS A H,VAN DEN OORD E J,RILEY B P,et al.Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia[J].Am J Psychiatry,2005,162(10):1824-1832.DOI:10.1176/appi.ajp.162.10.1824.
• [38]CORVIN A,DONOHOE G,NANGLE J M,et al.A dysbindin risk haplotype associated with less severe manictype symptoms in psychosis[J].Neurosci Lett,2008,431(2):146-149.DOI:10.1016/j.neulet.2007.11.031.
• [39]WIRGENES K V,DJUROVIC S,AGARTZ I,et al.Dysbindin and d-amino-acid-oxidase gene polymorphisms associated with positive and negative symptoms in schizophrenia[J].Neuropsychobiology,2009,60(1):31-36.DOI:10.1159/000235799.
• [40]WESSMAN J,PAUNIO T,TUULIO-HENRIKSSON A,et al.Mixture model clustering of phenotype features reveals evidence for association of DTNBP1 to a specific subtype of schizophrenia[J].Biol Psychiatry,2009,66(11):990-996.DOI:10.1016/j.biopsych.2009.05.034.
• [41]SUN Y H,SHEN Y,XU Q.DTNBP1 gene is associated with some symptom factors of schizophrenia in Chinese Han nationality[J].Chin Med Sci J,2010,25(2):85-89.DOI:10.1016/s1001-9294(10)60027-2.
• [42]周洪莉,张祚,周吉银.GABA能神经系统与神经退行性病变的研究进展[J].中国实用神经疾病杂志,2019,22(1):86-92.DOI:10.12083/SYSJ.2019.01.018.
• [43]赵绍锋.奥氮平对精神分裂症患者认知功能障碍的改善作用[J].中国实用神经疾病杂志,2017,20(16):78-80.
• [44]VARELA-GOMEZ N,MATA I,PEREZ-IGLESIAS R,et al.Dysbindin gene variability is associated with cognitive abnormalities in first-episode non-affective psychosis[J].Cogn Neuropsychiatry,2015,20(2):144-156.DOI:10.1080/13546805.2014.991780.
• [45]HASHIMOTO R,NOGUCHI H,HORI H,et al.Association between the dysbindin gene(DTNBP1)and cognitive functions in Japanese subjects[J].Psychiatry Clin Neurosci,2009,63(4):550-556.DOI:10.1111/j.1440-1819.2009.01985.x.
• [46]TAN G K,TEE S F,TANG P Y.Genetic association of single nucleotide polymorphisms in dystrobrevin binding protein 1 gene with schizophrenia in a Malaysian population[J].Genet Mol Biol,2015,38(2):138-146.DOI:10.1590/S1415-4757382220140142.
• [47]BAKANIDZE G,BRANDL E J,HUTZLER C,et al.Association of Dystrobrevin-Binding Protein 1 Polymorphisms with Sustained Attention and Set-Shifting in Schizophrenia Patients[J].Neuropsychobiology,2016,74(1):41-47.DOI:10.1159/000450550.
• [48]BAEK J H,KIM J S,RYU S,et al.Association of genetic variations in DTNBP1 with cognitive function in schizophrenia patients and healthy subjects[J].Am JMed Genet B Neuropsychiatr Genet,2012,159B(7):841-849.DOI:10.1002/ajmg.b.32091.
• [49]STEFANIS N C,TRIKALINOS T A,AVRAMOPOULOSD.Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level[J].Biol Psychiatry,2007,62(7):784-792.DOI:10.1016/j.biopsych.2006.11.015.