AbstractThe etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls.

摘要抽动障碍（TDs）的病因尚不清楚，尽管有几条证据表明免疫系统参与了发病机制。在这里，我们旨在确定TD儿童中促炎和抗炎细胞因子的表达水平，并将其与健康对照组进行比较。

Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette’s disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder.

此外，我们还评估了它们与TD组临床变量的关联。在研究期间，招募了88名抽动障碍儿童和111名健康对照儿童。大多数抽动障碍儿童被诊断为图雷特氏病或持久性运动抽动障碍，分别为47例、53.4%和49例，其余儿童被诊断为持久性发声抽动障碍。的2例、2.3%。的2例。的2例患儿被诊断为患有抽动障碍的2例患儿。的2例患儿被诊断为抽动障碍。的2例患儿。的2例患儿。的2例患儿的2例患儿的2例患儿的2例患儿的2例患儿的2例患儿的2例患儿的2例患儿的2例患儿的2例。

We found that children with tic disorders had significantly elevated levels of IL-1β, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity.

我们发现抽动障碍儿童的IL-1β，TNF-α，IL-6和IL-4表达水平显着升高，而我们发现抽动障碍儿童的IL-17表达水平较低。我们的研究结果提供了TD儿童细胞因子表达的分子景观，这可能表明促炎状态不受合并症和症状严重程度的影响。

Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions..

描述免疫系统改变对抽动障碍发病机制的贡献可能为更好的治疗干预铺平道路。。

IntroductionTic disorders in the DSM-5 include Tourette Syndrome (TS), persistent (chronic) motor/vocal tic disorder (CMVTD), and provisional tic disorder1,2. The consensus is that these disorders arise due to impaired function of the cortical-striatal-thalamic-cortical circuits, and aberrations of associated neurotransmitters may include dopamine, serotonin, gamma-aminobutyric acid (GABA), glutamate, acetylcholine, noradrenaline, and histamine3,4,5.

介绍DSM-5中的疾病包括Tourette综合征（TS），持续性（慢性）运动/声音抽动障碍（CMVTD）和暂时性抽动障碍1,2。共识是，这些疾病是由于皮质-纹状体-丘脑-皮质回路的功能受损引起的，相关神经递质的异常可能包括多巴胺，血清素，γ-氨基丁酸（GABA），谷氨酸，乙酰胆碱，去甲肾上腺素和组胺3,4,5。

The etiology of tic disorders is complex and involves multiple genetic, environmental, psychological, and immunological factors as well as their interactions3,4,5.Tic disorders are characterized by high heritability and familial transmission. Candidate susceptibility genes included CNTNAP2, NLGN4, SLITRK1, HDC, IMMP2L, DRD2, DRD4, MAO-A, and GABAA receptors.

抽动障碍的病因复杂，涉及多种遗传，环境，心理和免疫因素及其相互作用3,4,5。抽动障碍的特征是遗传力高和家族传播。候选易感基因包括CNTNAP2，NLGN4，SLITRK1，HDC，IMMP2L，DRD2，DRD4，MAO-A和GABAA受体。

These implicated potassium channels, membrane proteins, histidine metabolism, mitochondrial functioning, dopaminergic, GABAergic, and monoamine neurotransmitter function in etiology3,4,5,6. Genome wide association studies (GWAS) as well as studies evaluating single nucleotide polymorphisms (SNPs) suggest that tic disorders are polygenetic and the interaction between genetic predisposition and environmental factors increase the risk of their occurrence 3,4,5,7.Studies on the environmental factors affecting the development of tic disorders have focused on prenatal, perinatal, and other developmental periods.

。全基因组关联研究（GWAS）以及评估单核苷酸多态性（SNP）的研究表明，抽动障碍是多基因的，遗传易感性和环境因素之间的相互作用会增加其发生的风险3,4,5,7。影响抽动障碍发展的环境因素的研究主要集中在产前，围产期和其他发育时期。

Tic disorders in the offspring were found to be associated with maternal stress, nausea/vomiting, and smoking/alcohol/cannabis use during pregnancy. Low birth weight and a reduction in Apgar scores after birth may also increase risk. Familial and psychological factors were not found to be related to the onset of tics, but to their exacerbation.

发现后代的抽动障碍与母亲的压力，恶心/呕吐以及怀孕期间吸烟/饮酒/大麻的使用有关。出生体重低和出生后Apgar评分降低也可能增加风险。未发现家族和心理因素与抽动症的发作有关，但与抽动症的恶化有关。

These factors may inclu.

这些因素可能包括。

Data availability

数据可用性

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

本研究中使用和/或分析的数据集可根据合理要求从通讯作者处获得。

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Download referencesAuthor informationAuthors and AffiliationsDepartment of Child and Adolescent Psychiatry, Baskent University School of Medicine, Dr. Turgut Noyan Medical and Research Center, Adana, TurkeyMeryem Ozlem KutukDepartment of Child and Adolescent Psychiatry, Bolu Abant Izzet, Baysal University School of Medicine, Bolu, TurkeyAli Evren TufanDepartment of Child and Adolescent Psychiatry, Harran University School of Medicine, Sanliurfa, TurkeyFethiye KilicaslanDepartment of Child and Adolescent Psychiatry, Private Practice, Istanbul, TurkeyCem Gokcen & Cigdem YektasDepartment of Child and Adolescent Psychiatry, Mersin University School of Medicine, Mersin, TurkeyGulen Guler AksuDepartment of Child and Adolescent Psychiatry, Celal Bayar University School of Medicine, Manisa, TurkeyHasan KandemirDepartment of Psychology, Ankara Gazi Mustafa Kemal Occupational and Environmental Diseases Hospital, Ankara, TurkeyFatma CelikDepartment of Child and Adolescent Psychiatry, Koc University School of Medicine, Istanbul, TurkeyTuba MutluerDepartment of Child and Adolescent Psychiatry, Pamukkale University School of Medicine, Denizli, TurkeyAhmet BuberDepartment of Child and Adolescent Psychiatry, Gaziantep University School of Medicine, Gaziantep, TurkeyMehmet Karadag & Zehra HangulDepartment of Child and Adolescent Psychiatry, Adana City Training and Research Hospital, Adana, TurkeyNurdan CobanDepartment of Child and Adolescent Psychiatry, Private Practice, Adana, TurkeySeyma CoskunDepartment of Psychiatry, Baskent University School of Medicine, Dr.

下载参考文献作者信息作者和所属机构巴斯肯特大学医学院儿童和青少年精神病学系，图尔古特·诺扬博士医学和研究中心，阿达纳，土耳其梅里姆·奥兹勒姆·库图克儿童和青少年精神病学系，博鲁·阿班特·伊兹泽特，巴伊萨尔大学医学院，博鲁，土耳其阿里·埃夫伦·图凡哈兰大学医学院儿童和青少年精神病学系，三留尔法，土耳其费提耶·基利卡斯兰儿童和青少年精神病学系，私人执业，伊斯坦布尔，土耳其塞姆·戈科恩和Cigdem-Yektas儿童和青少年精神病学系，土耳其默辛大学医学院，默辛，土耳其古伦古勒阿克苏儿童和青少年精神病学系，塞拉尔巴亚尔大学医学院，马尼萨，土耳其哈桑坎德米尔心理学系，安卡拉加齐穆斯塔法凯末尔职业和环境疾病医院，安卡拉，土耳其塞法特玛塞利克Koc大学医学院儿童和青少年精神病学系，伊斯坦布尔，土耳其图巴-穆特卢德儿童和青少年精神病学系，帕穆卡莱大学医学院，德尼兹利，土耳其艾哈迈特-布贝尔儿童和青少年精神病学系，加济安泰普大学医学院，加济安泰普，土耳其艾哈迈特-卡拉达格和泽拉-汉格尔儿童和青少年精神病学系，阿达纳市培训和研究医院，阿达纳，土耳其纽尔丹-科班德儿童和青少年精神病学系，私人诊所，阿达纳，土耳其西马-科斯库精神病学系，巴斯肯特大学医学院，博士。

Turgut Noyan Medical and Research Center, Adana, TurkeyEbru AltintasImmunocore Ltd, Abingdon, Oxford, UKUfuk AcikbasDepartment of Genetics and Bioengineering, Alanya Alaaddin Keykubat University, Alanya, TurkeyA.

Turgut Noyan医学和研究中心，Adana，TurkeyEbru AltintasImmunocore Ltd，牛津阿宾顿，UKUfuk Acikbas遗传与生物工程系，Alanya Alaaddin Keykubat大学，Alanya，TurkeyA。

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PubMed Google ScholarContributionsMOK, AET and OK conceived and designed the study. MOK, AET, FK, CG, GGA, CY, HK, FC, TM, AB, MK, NC, SC, ZH, EA, UA, AG, YA, BB and OK performed the research. MOK, AET, OK, FK analyzed the data. MOK, AET, FK and OK wrote, reviewed, and edited the manuscript.

PubMed Google ScholarContributionsMOK，AET和OK构思并设计了这项研究。MOK，AET，FK，CG，GGA，CY，HK，FC，TM，AB，MK，NC，SC，ZH，EA，UA，AG，YA，BB和OK进行了研究。MOK，AET，OK，FK分析了数据。MOK，AET，FK和OK撰写，审阅和编辑了手稿。

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Reprints and permissionsAbout this articleCite this articleKutuk, M.O., Tufan, A.E., Kilicaslan, F. et al. Cytokine expression profiles in children and adolescents with tic disorders.

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KeywordsTic disordersCytokinesImmune systemInflammationTourette syndrome

关键词疾病细胞因子免疫系统炎症Tourette综合征

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