{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:46:00Z","timestamp":1790189160019,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wuhan Medical Research Project in 2020","award":["WX20A13"],"award-info":[{"award-number":["WX20A13"]}]},{"name":"Wuhan Medical Research Project in 2020","award":["CTDSF-2021-03"],"award-info":[{"award-number":["CTDSF-2021-03"]}]},{"name":"the First Tip Cup Tic Disorder Scientific Research Fund Project","award":["WX20A13"],"award-info":[{"award-number":["WX20A13"]}]},{"name":"the First Tip Cup Tic Disorder Scientific Research Fund Project","award":["CTDSF-2021-03"],"award-info":[{"award-number":["CTDSF-2021-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and\/or vocal tics that commonly affect children\u2019s physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. Methods: We collected 94 samples of plasma and 69 samples of urine from 3\u201312-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. Results: The plasma levels of norepinephrine, glutamic acid, and \u03b3-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and \u03b3-aminobutyric acid in the 8\u201312-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). Conclusions: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD.<\/jats:p>","DOI":"10.3390\/brainsci12070880","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A Pilot Study on Plasma and Urine Neurotransmitter Levels in Children with Tic Disorders"],"prefix":"10.3390","volume":"12","author":[{"given":"Qiao-Qiao","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qian","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Marketing, Wuhan Kindstar Clinical Diagnostic Institute Co., Ltd., Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Marketing, Wuhan Kindstar Clinical Diagnostic Institute Co., Ltd., Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Marketing, Wuhan Kindstar Clinical Diagnostic Institute Co., Ltd., Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Chao","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Sheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wuhan Children\u2019s Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.5334\/tohm.442","article-title":"Merging the pathophysiology and pharmacotherapy of tics","volume":"8","author":"Augustine","year":"2019","journal-title":"Tremor Other Hyperkinet Mov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/jcpp.13445","article-title":"Prevalence of mental disorders in school children and adolescents in China: Diagnostic data from detailed clinical assessments of 17,524 individuals","volume":"63","author":"Li","year":"2022","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.pediatrneurol.2012.05.002","article-title":"Prevalence of tic disorders: A systematic review and meta-analysis","volume":"47","author":"Knight","year":"2012","journal-title":"Pediatr. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/mds.26089","article-title":"Population prevalence of Tourette syndrome: A systematic review and meta-analysis","volume":"30","author":"Scharf","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1002\/mds.26766","article-title":"The prevalence of diagnosed tourette syndrome in Canada: A national population-based study","volume":"31","author":"Yang","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/B978-0-12-411546-0.00006-8","article-title":"Genetic susceptibility and neurotransmitters in Tourette syndrome","volume":"112","author":"Paschou","year":"2013","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_7","first-page":"2","article-title":"Determination and significance of serum dopamine in patients with tic disorder","volume":"27","author":"Xuan","year":"2006","journal-title":"J. Sun. Yat. Sen. Univ. Med. Sci."},{"key":"ref_8","first-page":"3","article-title":"The monoamine neurotransmitters changes and significances in tic disorder patients\u2019 serom","volume":"8","author":"Min","year":"2008","journal-title":"Nerv. Dis. Ment. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0028-3843(14)60039-6","article-title":"The analysis of selected neurotransmitter concentrations in serum of patients with Tourette syndrome","volume":"44","author":"Janik","year":"2010","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_10","first-page":"5","article-title":"Effects of Jianpi Zhidong Decoction on the neurotransmitters of tourette syndrome children","volume":"30","author":"Xue","year":"2015","journal-title":"Chin. J. Tradit. Chin. Med. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121805","DOI":"10.1016\/j.jchromb.2019.121805","article-title":"Validation of an improved liquid chromatography tandem mass spectrometry method for rapid and simultaneous analysis of plasma catecholamine and their metabolites","volume":"1129","author":"Yu","year":"2019","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.clinbiochem.2020.03.006","article-title":"Highly sensitive LC-MS\/MS analysis of catecholamines in plasma","volume":"82","author":"Bergmann","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.3724\/SP.J.1123.2017.06011","article-title":"Determination of urine catecholamines and metanephrines by reversed-phase liquid chromatography-tandem mass spectrometry","volume":"35","author":"Cheuk","year":"2017","journal-title":"Chin. J. Chromatogr."},{"key":"ref_14","first-page":"2279","article-title":"Physiology and pharmacology of neurotransmitter transporters","volume":"11","author":"Watts","year":"2021","journal-title":"Compr. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00702-020-02289-6","article-title":"Altered urinary tetrahydroisoquinoline derivatives in patients with Tourette syndrome: Reflection of dopaminergic hyperactivity?","volume":"128","author":"Capetian","year":"2021","journal-title":"J. Neural. Transm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/ana.21809","article-title":"Extrastriatal dopaminergic dysfunction in Tourette syndrome","volume":"67","author":"Steeves","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1176\/appi.ajp.159.8.1329","article-title":"Elevated intrasynaptic dopamine release in Tourette\u2019s syndrome measured by PET","volume":"159","author":"Singer","year":"2002","journal-title":"Am. J. Psychiatry."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e881","DOI":"10.1016\/j.wneu.2019.03.290","article-title":"Globus pallidus internus electric high-frequency stimulation modulates dopaminergic activity in the striatum of a rat model of Tourette syndrome","volume":"127","author":"Zhao","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1212\/WNL.0000000000007466","article-title":"Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders","volume":"92","author":"Pringsheim","year":"2019","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1002\/hbm.22793","article-title":"Similar striatal D2\/D3 dopamine receptor availability in adults with Tourette syndrome compared with healthy controls: A [(11) C]-(+)-PHNO and [(11) C]raclopride positron emission tomography imaging study","volume":"36","author":"Segura","year":"2015","journal-title":"Hum. Brain. Mapp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0306-4522(97)00565-4","article-title":"Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and heteroreceptor-mediated control of release","volume":"84","author":"Gobert","year":"1998","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s11940-010-0095-4","article-title":"Treatment of tics and tourette syndrome","volume":"12","author":"Singer","year":"2010","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nicl.2016.11.013","article-title":"Fronto-striatal glutamate in children with Tourette\u2019s disorder and attention-deficit\/hyperactivity disorder","volume":"13","author":"Naaijen","year":"2016","journal-title":"Neuroimage Clin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/brain\/aww285","article-title":"Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome","volume":"140","author":"Kanaan","year":"2017","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3174\/ajnr.A4547","article-title":"GABA and glutamate in children with primary complex motor stereotypies: An 1H-MRS Study at 7T","volume":"37","author":"Harris","year":"2016","journal-title":"Am. J. Neuroradiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1093\/brain\/aws104","article-title":"Widespread abnormality of the \u03b3-aminobutyric acid-ergic system in Tourette syndrome","volume":"135","author":"Lerner","year":"2012","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.neuron.2015.12.025","article-title":"A primary role for nucleus accumbens and related limbic network in vocal tics","volume":"89","author":"McCairn","year":"2016","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fnsys.2017.00076","article-title":"Dopamine modulates serotonin innervation in the drosophila brain","volume":"11","author":"Niens","year":"2017","journal-title":"Front. Syst. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hildonen, M., Levy, A.M., Dahl, C., Bjerregaard, V.A., Birk M\u00f8ller, L., Guldberg, P., Debes, N.M., and T\u00fcmer, Z. (2021). Elevated expression of SLC6A4 encoding the serotonin transporter (SERT) in Gilles de la Tourette syndrome. Genes, 12.","DOI":"10.3390\/genes12010086"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/s41386-020-0671-6","article-title":"Cerebrospinal fluid endocannabinoid levels in Gilles de la Tourette syndrome","volume":"45","author":"Bindila","year":"2020","journal-title":"Neuropsychopharmacology"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/7\/880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:42:30Z","timestamp":1760139750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/7\/880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,4]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["brainsci12070880"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12070880","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,4]]}}}