A Study On The Correlation Between Tic Disorders And Plasma Neurotransmitters In Children

BackgroundTic disorders(TD)are involuntary,recurrent,sudden and rapid disorders that begin in childhood or adolescence.A group of syndromes characterized by repetitive,anrhythmic motor and/or vocal twitches in one or more sites.The clinical manifestations are varied and may be associated with a variety of comorbidities.Some children present as refractory.According to the clinical characteristics and course of disease,TD was divided into three types:transient tic disorders,chronic tic disorders and Tourette syndrome(TS).The onset age was between 5 to 10 years old,and the most serious was between 10 to 12 years old.There were more males than females,and the ratio of males to females was(3～5):1.The etiology of tic disorder is complex and has not yet been fully defined.The most studied etiology of tic disorder is the combination of vocalization and various movements,which may be the result of the interaction of genetic factors,neurophysiology,neurobiochemical factors and environmental factors.Among them,the relationship between neurobiochemical factors and tic disorders is very complex and has not yet been determined.Neurotransmitters are chemical substances that transmit signals between neurons and between neurons and target cells.As transmitters of information,neurotransmitters play an important role in central and peripheral nervous systems.Neurotransmitters are synthesized in neurons,released into the synaptic cleft through the presynaptic membrane,and then act on the postsynaptic membrane to bind to receptors in the postsynaptic membrane,thus playing a physiological role.Abnormalities in any part of the process can have a profound impact on physiological function,leading to neuropsychiatric problems.Central neurotransmitters are divided into biological amines,amino acids,acetylcholine and peptides.At present,it is generally believed that children with tic disorders may have the following abnormalities:excessive dopamine activity or receptor hypersensitivity;Glutamate levels in the globus pallidus and other parts increased;noradrenaline dysfunction;The level of 5-hydroxytryptamine decreased;Insufficient acetylcholine,decreased activity;The inhibitory function of y-aminobutyric acid was decreased;dynorphin dysfunction in basal ganglia and hypothalamus.The diagnosis of tic disorders mainly based on history of tic and clinical manifestations,often use the United States in the fifth edition of the diagnostic statistical manual of mental disease diagnosis standard of tic disorders to assess its severity,lack of objective basis,the need to rule out other diseases diagnosis,some children with atypical clinical manifestations or can incorporate other comorbidities,so clinical diagnosis of tic disorders may appear misdiagnosis and missed diagnosis,so reliable laboratory diagnosis basis can help the diagnosis and differential,and offers a new train of thought for treatment and prognosis.ObjectiveStudy the factors of children with tic disorders,determination of children with tic disorders plasma dopamine(DA),epinephrine(E)and norepinephrine(NE)and serotonin(5-HT)and glutamate(Glu)and tyrosine(Tyr),tryptophan(Try)and gamma-aminobutyric acid(GABA)levels,such as plasma neurotransmitter levels to explore the correlation of children with tic disorders.MethodsSubjects:In this study,99 children with tic disorders(case group)and 60 healthy children(control group)were selected to detect plasma neurotransmitter levels.Detection method:Collecting venous blood(3mL-5mL)from the case group and the control group at morning and placed in the heparin anticoagulant tube,centrifuged at 10000r/min at-4℃ for 10 min,and the plasma was taken and stored at-20℃ for later use.The contents of neurotransmitters(including dopamine,epinephrine,norepinephrine,5-hydroxytryptamine,glutamic acid,tyrosine,tryptophan andγ-aminobutyric acid)in plasma were analyzed by UPLC-MS/MS.All data were analyzed by statistical software SPSS 22.0.The quantitative data of normal distribution in each group was represented by X±S,and we will use the t-test to compare data of the groups.The quantitative data of non-normal distribution are represented by P50(P25,P75),and the-non-parameter test is used for inter-group comparison.Count data expressed in frequency and adopted the χ2 test.P<0.05 was considered statistically significant,while P<0.01 was considered obviously statistically significant.Binary Logistic regression analysis was used to determine whether the indicators with statistical significance could be used to diagnose tic disorders.Receiver operating characteristic curve would be used to further evaluate their diagnostic value.And we will count the area under the ROC curve to value the diagnostic.Results1.Compared with the control group,plasma dopamine was significantly increased in the case group,and the difference was statistically significant(Z=-7.870,P=0.001).2.Compared with the control group,plasma norepinephrine was increased in the case group,and the difference was statistically significant(Z=-3.017,P=0.003).3.There was no significant difference in plasma neurotransmitters levels among the tic disorder subtypes.4.In the case group,the area under the plasma dopamine curve(AUC)was 0.873.When the cutoff value was 0.1255,the sensitivity was 75.8%and the specificity was 100%.5.In the case group,the plasma area under the norepinephrine curve(AUC)was 0.643,and when the cutoff value was 5.024,the sensitivity and specificity were 32.3%and 96.7%.Conclusions1.Children with tic disorders may have a higher level of plasma dopamine and norepinephrine.There was no significant difference of neurotransmitters levels in plasma among the subtypes of tic disorders.2.The level of plasma dopamine provides a possible neurobiochemical basis for the diagnosis of tic disorders in children.