ABSTRACT
Abnormal levels of some peripheral cytokines have been reported in children patients with tic disorders (TDs), but none of these cytokines can be a biomarker for this disease. Our aim was to systemically profile differentially expressed cytokines (DECs) in the blood of TD patients, examine their associations with TD development, and identify from them potential biomarkers for the prediction and management of the risk for TDs. In this study, a cytokine array capable of measuring 105 cytokines was used to screen for DECs in the plasma from 53 comorbidity-free and drug-naïve TD patients and 37 age-matched healthy controls. DECs were verified by ELISA and their associations with TD development were evaluated by binary logistic regression analysis. Elevation of a set of cytokines was observed in TD patients compared with controls, including previously uncharacterized cytokines in tic disorders, CCL5, Serpin E1, Thrombospondin-1, MIF, PDGF-AA, and PDGF-AB/BB. Further analysis of DECs revealed a significant association of elevated CCL5 with TD development (p = 0.005) and a significant ROC curve for CCL5 as a risk factor [AUC, 0.801 (95% CI: 0.707-0.895), p < 0.0001]. Conclusion: This study identifies associations of a set of circulating cytokines, particularly CCL5 with TD development, and provides evidence that high blood CCL5 has potential to be a risk factor for TD development. Clinical Trial Registration: identifier ChiCTR-2000029616.
ABSTRACT
Study objectives: To characterize sleep disturbances and sleep patterns in children with Tic disorder (TD), and explore their association with TD severity and types. Methods: A case-control study was conducted in 271 children with TD recruited from a clinical setting and 271 non-TD children recruited from a primary school, matched by age (mean = 8.47 years, SD = 1.53 years) and gender (15.1% female). The Children's Sleep Habits Questionnaire (CSHQ) was used to assess sleep patterns and sleep disturbances. The TD types and severity were assessed with the Yale Global Tic Severity Scale (YGTSS). Results: The TD children scored higher on CSHQ total score than non-TD group (t = 29.50, p < 0.001) and demonstrated severer global sleep disturbance. Compared to non-TD children, TD children presented with increased risks for global sleep disturbance (aOR: 1.95; 95% CI = 1.20-3.06), and most specific sleep disturbances, including bedtime resistance (aOR: 3.15; 95% CI = 1.96-5.06), sleep onset delay (aOR: 3.43; 95% CI = 1.58-7.46), sleep anxiety (aOR: 2.83; 95%CI = 1.83-4.38), parasomnias (aOR: 3.68; 95% CI = 2.02-6.62), night waking (aOR: 9.29; 95% CI = 2.64-32.65), sleep disordered breathing (aOR: 1.72; 95% CI = 1.03-2.90) and daytime sleepiness (aOR: 1.72; 95% CI = 1.09-2.74). Children with mild and moderate tics, Provisional Tic Disorder (PTD), Chronic Tic Disorder (CTD) and Tourette Syndrome (TS) presented with more global and more specific sleep disturbances. In addition, combined ADHD, etc. Conclusion: Children with TD are major risks for increased sleep disturbances, especially for those with severe and chronic symptoms. Furthermore, comorbid ADHD increases risk in certain areas of sleep. These findings highlight the importance to consider sleep outcomes in the assessment and treatment for children with TD.