5-羟色胺在孤独症谱系障碍中的研究进展
Research Progress of Serotonin in Autism Spectrum Disorders
DOI: 10.12677/IJPN.2015.43003, PDF, HTML, XML, 下载: 2,871  浏览: 17,388 
作者: 王丽丽, 杜琳, 单玲, 冯俊燕, 贾飞勇*:吉林大学第一医院小儿神经康复科,吉林 长春
关键词: 孤独症谱系障碍5-HT5-HTTAutism Spectrum Disorder 5-HT 5-HTT
摘要: 孤独症谱系障碍(ASD)是一组以不同程度的社会交流、交往障碍和限制性、重复性行为、兴趣及活动异常为主要特征的发育行为障碍性疾病。ASD的发病率逐渐增加,但其病因不明。5-羟色胺(5-HT)是一种在人体中广泛存在的单胺类神经递质,对神经精神活动等具有一定的调节作用。研究发现,ASD患者的5-HT水平在外周血中升高,脑内降低,这种反常现象在ASD患者中较为常见。且5-HT转运体(5-HTT)基因异于常人。因此,5-HT系统的异常可能是影响ASD的一项危险因素。
Abstract: Autism spectrum disorder (ASD) is a group of developmental behavioral disorders which have the main features like different levels of social interaction and communication barriers, restrictive and repetitive behaviors and abnormal interests and activities. The onset of ASD shows a trend of increase year by year, but its etiology is unknown. Serotonin is a monoamine neurotransmitter which is widely present in the human body and has a regulatory role in other neuropsychiatric events. The study found that the 5-HT of patients with ASD level increased in peripheral blood and decreased in the brain. This anomaly was common in ASD patients. 5-HT transporter gene was different from ordinary people. Therefore, the abnormality of 5-HT system may be a risk factor for ASD.
文章引用:王丽丽, 杜琳, 单玲, 冯俊燕, 贾飞勇. 5-羟色胺在孤独症谱系障碍中的研究进展[J]. 国际神经精神科学杂志, 2015, 4(3): 13-18. http://dx.doi.org/10.12677/IJPN.2015.43003

参考文献

[1] 李洪华, 姜慧轶, 杜琳, 等 (2012) 儿童孤独症的早期筛查与诊断研究进展. 中国实验诊断学, 16, 2147-2150.
[2] Mann, J.J. (1999) Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Archives of Internal Medicine, 21, 99S-105S.
http://dx.doi.org/10.1016/S0893-133X(99)00040-8
[3] Richards, J.B., Papaioannou, A., Adachi, J.D., et al. (2007) Effect of selective serotonin reuptake inhibitors on the risk of fracture. Archives of Internal Medicine, 167, 188-194.
http://dx.doi.org/10.1001/archinte.167.2.188
[4] Vestergaard, P., Rejnmark, L. and Mosekilde, L. (2008) Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcified Tissue International, 82, 92-101.
http://dx.doi.org/10.1007/s00223-007-9099-9
[5] Munafo, M.R., Durrant, C., Lewis, G., et al. (2009) Gene X environment interactions at the serotonin transporter locus. Biological Psychiatry, 65, 211-219.
http://dx.doi.org/10.1016/j.biopsych.2008.06.009
[6] Schain, R.J. and Freedman, D.X. (1961) Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. Pediatrics, 58, 315-320.
http://dx.doi.org/10.1016/S0022-3476(61)80261-8
[7] Whitehouse, A.J., Holt, B.J., Serralha, M., Holt, P.G., Hart, P.H. and Kusel, M.M. (2013) Maternal vitamin D levels and the autism phenotype among offspring. Journal of Autism and Developmental Disorders, 43, 1495-1504.
http://dx.doi.org/10.1007/s10803-012-1676-8
[8] Reed, P. and McCarthy, J. (2012) Cross-modal attentions witching is impaired in autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 947-953.
http://dx.doi.org/10.1007/s10803-011-1324-8
[9] Gabriele, S., Sacco, R. and Persico, A.M. (2014) Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis. European Neuropsychopharmacology, 24, 919-929.
http://dx.doi.org/10.1016/j.euroneuro.2014.02.004
[10] Kolevzon, A., Newcorn, J.H., Kryzac, L., Watner, D., Chaplin, W., Smith, C.J., Hollander, E., Cook, E.H. and Silverman, J.M. (2010) The relationship between repetitive behaviors and whole blood serotonin in autism. Psychiatry Research, 175, 274-276.
http://dx.doi.org/10.1016/j.psychres.2009.02.008
[11] Moul, C., Dobson-Stone, C., Brennan, J., Hawes, D. and Dadds, M. (2013) An exploration of the serotonin system in antisocial boys with high levels of callous-unemotional traits. PLoS ONE, 8, e56619.
http://dx.doi.org/10.1371/journal.pone.0056619
[12] 李思特, 李雪荣, 张献共, 朱荣华, 罗学荣, 苏林雁, 等 (2003) 儿童孤独症血浆5–羟色胺的测定. 中国神经精神疾病杂志, 4, 279-281.
[13] 焦公凯, 王伟勇, 张志珺, 方群, 邹冰, 王晨阳, 等 (2003) 儿童孤独症血浆5–羟色胺水平的对照研究. 临床精神医学杂志, 6, 334-335.
[14] Mostafa, G.A. and Al-Ayadhi, L.Y. (2011) A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children. Journal of Neuroinflammation, 8, 71.
http://dx.doi.org/10.1186/1742-2094-8-71
[15] Hubbard, A.L., McNealy, K., Scott-Van Zeeland, A.A., Callan, D.E., Bookheimer, S.Y. and Dapretto, M. (2012) Altered integration of speech and gesture in children with autism spectrum disorders. Brain and Behavior, 2, 606-619.
http://dx.doi.org/10.1002/brb3.81
[16] Chantiluke, K., Barrett, N., Giampietro, V., Santosh, P., Brammer, M., Simmons, A., Murphy, D.G. and Rubia, K. (2015) Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD. Psychopharmacology, 232, 2071-2082.
http://dx.doi.org/10.1007/s00213-014-3837-2
[17] Hollander, E., Soorya, L., Chaplin, W., Anagnostou, E., Taylor, B.P., Ferretti, C.J., Wasserman, S., Swanson, E. and Settipani, C. (2012) A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. American Journal of Psychiatry, 169, 292-299.
http://dx.doi.org/10.1176/appi.ajp.2011.10050764
[18] Jaiswal, P., Mohanakumar, K.P. and Rajamma, U. (2015) Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders. Neuroscience & Biobehavioral Reviews, 55, 413-431.
http://dx.doi.org/10.1016/j.neubiorev.2015.05.013
[19] Mulder, E.J., Anderson, G.M., Kemperman, R.F.J., Oosterloo-Duinkerken, A., Minderaa, R.B. and Kema, I.P. (2010) Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals. Neuropsychobiology, 61, 27-32.
http://dx.doi.org/10.1159/000258640
[20] Beliveau, V., Svarer, C., Frokjaer, V.G., Knudsen, G.M., Greve, D.N. and Fisher, P.M. (2015) Functional connectivity of the dorsal and median raphe nuclei at rest. Neuroimage, 116, 187-195.
http://dx.doi.org/10.1016/j.neuroimage.2015.04.065
[21] Witteveen, J.S., Middelman, A., van Hulten, J.A., Martens, G.J., Homberg, J.R. and Kolk, S.M. (2013) Lack of serotonin reuptake during brain development alters rostral raphe-prefrontal network formation. Frontiers in Cellular Neuroscience, 7, 143.
[22] Bonnin, A. and Levitt, P. (2012) Placental source for 5-HT that tunes fetal brain development. Neuropsychobiology, 37, 299-300.
http://dx.doi.org/10.1038/npp.2011.194
[23] Migliarini, S., Pacini, G., Pelosi, B., Lunardi, G. and Pasqualetti, M. (2013) Lack of brain serotonin affects postnatal development and serotonergic neuronal circuitry formation. Molecular Psychiatry, 18, 1106-1118.
http://dx.doi.org/10.1038/mp.2012.128
[24] Nakamura, K., Sekine, Y., Ouchi, Y., Tsujii, M., Yoshikawa, E., Futatsubashi, M., et al. (2010) Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Archives of General Psychiatry, 67, 59-68.
http://dx.doi.org/10.1001/archgenpsychiatry.2009.137
[25] Adamsen, D., Ramaekers, V., Ho, H.T.B., Britschgi, C., Rüfenacht, V., Meili, D., et al. (2014) Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene. Molecular Autism, 5, 43.
http://dx.doi.org/10.1186/2040-2392-5-43
[26] Chugani, D.C., Muzik, O., Rothermel, R., Behen, M., Chakraborty, P., Mangner, T., et al. (1997) Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Annals of Neurology, 42, 666-669.
http://dx.doi.org/10.1002/ana.410420420
[27] Viaggi, C., Gerace, C., Pardini, C., Corsini, G.U. and Vaglini, F. (2015) Serotonin abnormalities in engrailed-2 knockout mice: New insight relevant for a model of autism spectrum disorder. Neurochemistry International, 87, 34-42.
http://dx.doi.org/10.1016/j.neuint.2015.05.004
[28] Mashael, A.G., Laila, A.A. and Afaf, E.A. (2014) Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid-induced neurotoxicity in rodent model of autism. BMC Neuroscience, 25, 34.
[29] Boylan, C.B., Blue, M.E. and Hohmann, C.F. (2007) Modeling early cortical serotonergic deficits in autism. Behavioural Brain Research, 176, 94-108.
http://dx.doi.org/10.1016/j.bbr.2006.08.026
[30] Angoa-Pérez, M., Kane, M.J., Sykes, C.E., Perrine, S.A., Church, M.W. and Kuhn, D.M. (2014) Brain serotonin determines maternal behavior and offspring survival. Genes, Brain and Behavior, 13, 579-591.
http://dx.doi.org/10.1111/gbb.12159
[31] Angoa-Pérez, M., Kane, M.J., Briggs, D.I., Sykes, C.E., Shah, M.M., Francescutti, D.M., Rosenberg, D.R., Thomas, D.M. and Kuhn, D.M. (2012) Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity. Journal of Neurochemistry, 121, 974-984.
http://dx.doi.org/10.1111/j.1471-4159.2012.07739.x
[32] Mosienko, V., Bert, B., Beis, D., Matthes, S., Fink, H., Bader, M. and Alenina, N. (2012) Exaggerated aggression and decreased anxiety in mice deficient in brain serotonin. Translational Psychiatry, 29, e122.
http://dx.doi.org/10.1038/tp.2012.44
[33] Mosienko, V., Beis, D., Pasqualetti, M., Waider, J., Matthes, S., Qadri, F., Bader, M. and Alenina, N. (2015) Life without brain serotonin: Reevaluation of serotonin function with mice deficient in brain serotonin synthesis. Behavioural Brain Research, 277, 78-88.
http://dx.doi.org/10.1016/j.bbr.2014.06.005
[34] Flood, Z.C., Engel, D.L., Simon, C.C., Negherbon, K.R., Murphy, L.J., Tamavimok, W., Anderson, G.M. and Janušonis, S. (2012) Brain growth trajectories in mouse strains with central and peripheral serotonin differences: Relevance to autism models. Neuroscience, 17, 286-295.
http://dx.doi.org/10.1016/j.neuroscience.2012.03.010
[35] Takumi, T. (2010) A humanoid mouse model of autism. Brain and Development, 32, 753-758.
http://dx.doi.org/10.1016/j.braindev.2010.05.001
[36] 柳文华, 张兰 (2010) 五羟色胺转运体基因多态性与情感障碍关联研究. 精神医学杂志, 3, 224-227.
[37] Caspi, A., Hariri, A.R., Holmes, A., Uher, R. and Moffitt, T.E. (2010) Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509-527.
http://dx.doi.org/10.1176/appi.ajp.2010.09101452
[38] 徐莉萍, 谢永标, 赵爱玲, 李雪荣 (2006) 品行障碍患者5–羟色胺转运体基因遗传多态性研究. 中国行为医学科学, 7, 588-590.
[39] Campbell, N.G., Zhu, C.B., Lindler, K.M., Yaspan, B.L., Kistner-Griffin, E., Hewlett, W.A., et al. (2013) Rare coding variants of the adenosine A3 receptor are in-creased in autism: On the trail of the serotonin transporter regulome. Molecular Autism, 4, 28.
http://dx.doi.org/10.1186/2040-2392-4-28
[40] Coutinho, A.M., Sousa, I., Martins, M., Correia, C., Morgadinho, T., Bento, C., et al. (2007) Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levels. Human Genetics, 121, 243-256.
http://dx.doi.org/10.1007/s00439-006-0301-3
[41] Kolevzon, A., Lim, T., Schmeidler, J., Martello, T., Cook Jr., E.H. and Silverman, J.M. (2014) Self-injury in autism spectrum disorder: An effect of serotonin transporter gene promoter variants. Psychiatry Research, 220, 987-990.
http://dx.doi.org/10.1016/j.psychres.2014.09.018
[42] Li, D. and He, L. (2007) Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Molecular Psychiatry, 12, 47-54.
http://dx.doi.org/10.1038/sj.mp.4001890
[43] 尤劲松, 胡随瑜, 张宏耕 (2003) 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. 中华精神科杂志, 3, 132-134.