{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:01:20Z","timestamp":1780038080058,"version":"3.53.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tic disorders (TD) are diagnosed mainly through clinical observation, and accessible peripheral biomarkers that reflect neurobiological alterations remain limited. Brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) are biologically relevant to synaptic plasticity and neurochemical regulation. This study aimed to investigate serum BDNF and 5-HT levels in children with TD and to explore their associations with disease severity and clinical subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 125 children with TD and 100 age- and sex-matched healthy controls were enrolled. Serum BDNF and 5-HT concentrations were measured using enzyme-linked immunosorbent assay (ELISA). TD patients were further classified into mild and moderate-to-severe groups according to the Yale Global Tic Severity Scale. Biomarker differences across severity strata and TD subtypes were analyzed, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum BDNF levels were significantly lower in TD patients than in healthy controls and declined further in moderate-to-severe cases. In contrast, serum 5-HT levels did not differ between mild TD and HC but were significantly reduced in moderate-to-severe TD compared with mild cases. ROC analysis showed that BDNF (AUC 0.705, 95% CI 0.637\u20130.772) had modest discriminative ability for identifying TD and both BDNF (AUC 0.760, 95% CI 0.678\u20130.842) and 5-HT (AUC 0.652, 95% CI 0.555\u20130.749) were useful in distinguishing disease severity. Logistic regression identified sleep disturbances, family history of TD, and decreased BDNF were independently associated with TD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reduced serum BDNF was associated with disease presence and severity, whereas decreased 5-HT was mainly related to greater symptom severity. Given the modest ROC performance, serum BDNF and 5-HT may provide auxiliary biological information for pediatric tic disorders, but their clinical application requires validation in larger multicenter cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1826133","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:01:33Z","timestamp":1780034493000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical significance of serum brain-derived neurotrophic factor and serotonin levels in children with tic disorders"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiaoxia","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tongde Hospital of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongde Hospital of Zhejiang Province","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University (Hangzhou First People\u2019s Hospital)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University (Hangzhou First People\u2019s Hospital)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s00787-021-01842-2","article-title":"European Clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part I: assessment","volume":"31","author":"Szejko","year":"2022","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/s1474-4422(22)00303-9","article-title":"Tourette syndrome: clinical features, pathophysiology, and treatment","volume":"22","author":"Johnson","year":"2023","journal-title":"Lancet Neurol"},{"key":"B3","doi-asserted-by":"publisher","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":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.3390\/jcm10112479","article-title":"A comprehensive review of tic disorders in children","author":"Ueda","year":"2021","journal-title":"J Clin Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/1471-2393-14-53","article-title":"Prenatal risk factors for tourette syndrome: a systematic review","volume":"14","author":"Chao","year":"2014","journal-title":"BMC Pregnancy Childbirth"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3588043","DOI":"10.1155\/ppc\/3588043","article-title":"The fingerprints of fetal hormones: investigating tic disorder\u2019s origins through 2D: 4D digit ratio analysis","volume":"2026","author":"\u015eahin","year":"2026","journal-title":"Perspect Psychiatr Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/ijms22020853","article-title":"Immunological dysfunction in Tourette syndrome and related disorders","volume":"22","author":"Hsu","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.3390\/biomedicines12081761","article-title":"BDNF-Regulated Modulation of striatal circuits and implications for Parkinson\u2019s disease and dystonia","volume":"12","author":"Wolf","year":"2024","journal-title":"Biomedicines"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1523\/eneuro.0238-21.2023","article-title":"Identification of novel BDNF-specific corticostriatal circuitries","volume":"10","author":"Ehinger","year":"","journal-title":"eNeuro"},{"key":"B11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cell.2021.12.003","article-title":"BDNF Signaling in context: from synaptic regulation to psychiatric disorders","volume":"185","author":"Wang","year":"2022","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"595","DOI":"10.7916\/d8h14jtx","article-title":"Merging the pathophysiology and pharmacotherapy of tics","volume":"8","author":"Augustine","year":"2018","journal-title":"Tremor Other Hyperkinet Mov (N Y)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1089\/cap.1993.3.11","article-title":"Is there a role of serotonin in the disruptive behavior disorders? A literature review","volume":"3","author":"Zubieta","year":"1993","journal-title":"J Child Adolesc Psychopharmacol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1038\/s41598-018-37710-4","article-title":"Serotonin transporter binding is increased in Tourette syndrome with obsessive compulsive disorder","volume":"9","author":"M\u00fcller-Vahl","year":"2019","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"880","DOI":"10.3390\/brainsci12070880","article-title":"A pilot study on plasma and urine neurotransmitter levels in children with tic disorders","volume":"12","author":"Qian","year":"2022","journal-title":"Brain Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.bj.2022.01.008","article-title":"Current understanding of the genetics of Tourette syndrome","volume":"45","author":"Lin","year":"2022","journal-title":"Biomed J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/wps.20989","article-title":"DSM-5-TR: overview of what\u2019s new and what\u2019s changed","volume":"21","author":"First","year":"2022","journal-title":"World Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.pediatrneurol.2023.04.013","article-title":"Moderating role of depression on the association of tic severity with functional impairment in children","volume":"144","author":"Sadeh","year":"2023","journal-title":"Pediatr Neurol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1097\/00004583-198907000-00015","article-title":"The Yale global tic severity scale: initial testing of a clinician-rated scale of tic severity","volume":"28","author":"Leckman","year":"1989","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3389\/fpsyt.2016.00097","article-title":"Comorbidities, social impact, and quality of life in Tourette syndrome","volume":"7","author":"Eapen","year":"2016","journal-title":"Front Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8417","DOI":"10.3390\/ijms23158417","article-title":"BDNF Therapeutic mechanisms in neuropsychiatric disorders","volume":"23","author":"Bazzari","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3390\/ijms18020268","article-title":"Integral characterization of defective BDNF\/TrkB signalling in neurological and psychiatric disorders leads the way to new therapies","volume":"18","author":"Tejeda","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00221-016-4847-6","article-title":"BDNF And LTP-\/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome","volume":"235","author":"Marsili","year":"2017","journal-title":"Exp Brain Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1007\/s12640-019-00079-x","article-title":"Rhynchophylline attenuates Tourette syndrome via BDNF\/NF-\u03baB pathway in vivo and in vitro","volume":"36","author":"Long","year":"2019","journal-title":"Neurotox Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1038\/sj.npp.1301528","article-title":"Mechanisms of dopaminergic and serotonergic neurotransmission in Tourette syndrome: clues from an in vivo neurochemistry study with PET","volume":"33","author":"Wong","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e924658","DOI":"10.12659\/msm.924658","article-title":"Effects of jian-pi-zhi-dong decoction on the expression of 5-HT and its receptor in a rat model of Tourette syndrome and comorbid anxiety","volume":"26","author":"Wang","year":"2020","journal-title":"Med Sci Monit"},{"key":"B28","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1097\/cm9.0000000000001885","article-title":"Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion","volume":"135","author":"Li","year":"2022","journal-title":"Chin Med J (Engl)"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1826133\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:01:33Z","timestamp":1780034493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1826133\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":28,"alternative-id":["10.3389\/fped.2026.1826133"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1826133","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1826133"}}