Changes of Cytokines in Children With Tic Disorder

Tic disorder (TD) is a common childhood-onset disease associated with abnormal development of brain networks involved in the motor and sensory processing. The underlying pathophysiological mechanisms in TD are still unclear. An involvement of immune mechanisms in its pathophysiology has been proposed. This study investigates the association between the changes of cytokines and the etiology and development of TD. Different expressions of cytokines in a larger number of samples in our study may provide new insights to the field. The levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were evaluated in 1,724 patients who were clinically diagnosed with TD from 1 to 17.5 years old and 550 were from 6 months to 14.5 years old in the control group. We assessed the levels of cytokines according to the patient's medication status and the severity of the disease. Of the cytokines we investigated, the serum IL-6 concentration of children with TD was significantly higher than that of the control group, while the levels of other cytokines were lower in TD patients. In the patient group whose YTGSS score ranged from 1 to 9, the IL-4, IL-10, and IFN-γ levels increased in medication group compared to unmedication group. Our data suggested that the cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) may play an important role in the etiology and the severity in TD. Whether drug intervention in the early stage of tic disorder has a better effect on children needs further research.

Striatal Syntaixin 1A Plays a Protective Role Against Iminodipropionitrile Induced Tic Disorder Through Interaction with Dopamine Transporter

An important mechanism of Tic disorder (TD) is dysfunction in the dopamine (DA) system. Our pilot observation found the expression of Syntaxin 1A (STX1A), a presynaptic SNARE complex, changed in the striatum of TD animals. The present study aimed to clarify the biological role of striatal STX1A in the pathological state of TD and the specific mechanism of its regulation of the dopaminergic system. The TD rat model was established using iminodipropionitrile (IDPN). Adenovirus was used to modulate the expression of STX1A and dopamine transporter (DAT) in vivo and vitro. Primary culture of striatal dopaminergic neurons was performed for in-vitro observation of the DA reuptake, CO-IP analysis of the interaction between STX1A and DAT. First, using immunofluorescence staining, Western blotting, and qPCR, we found that the IDPN induced TD model had reduced striatal STX1A expression. In vitro, the DA content in the supernatant was significantly lower in the STX1A overexpressed group, and the intracellular DA content was significantly higher. Overexpression of STX1A in vivo partially counteracts the IDPN-induced TD-like behaviors, including bite time and head shaking time. Meanwhile, in-vivo knockdown of STX1A can aggravates TD-like behaviors. Further, DAT was overexpressed in vivo, and the TD-like behavior was alleviated. Interestingly, overexpression of DAT in the striatum resulted in increased levels of STX1A. In order to clarify the interaction between DAT and STX1A, the CO-IP analysis was conducted based on the protein of purified striatal dopaminergic neurons. Compared to the IgG control, the blots of DAT and STX1A showed significant binding of each other. Striatal STX1A expression is decreased in TD development, and STX1A plays an anti-TD role possibly through interaction with DAT, which maintains the DA reuptake. The exorbitant DA signal caused by STX1A inhibition drives the pathological stereotyped behavior.

Status of Medications Prescribed for Psychiatric Disorders in Korean Pediatric and Adolescent Patients

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (<20 years) who were diagnosed with schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, attention deficit-hyperactivity disorder (ADHD), or a tic disorder. Among these diseases, depressive episodes were the most common, followed by an anxiety disorder, ADHD, bipolar disorder, tic disorder, and schizophrenia. For each disease, prescriptions were categorized as full-label (approved indication with pediatric dosing in the package insert (PI)), partial-label (approved indication without pediatric dosing in the PI), and contraindication (contraindicated for the specific pediatric age in the PI). For schizophrenia, major depressive disorder, and anxiety disorder, more than 50% of the patients were prescribed partial-labeled medications. Additionally, more than 5% of patients with major depressive disorder were prescribed medications that were contraindicated for their age group. Our findings reveal that children with full-labeled psychiatric conditions are commonly administered drugs that are not explicitly approved for either their disease state or age, including off-label and unlicensed drugs. To use pharmaceuticals more safely, expanding drug indications using real-world data are needed.

Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy

Patients with autism spectrum disorder (ASD) display distinctive neurophysiological characteristics associated with significant cognitive, emotional, and behavioral symptoms. Transcranial direct current stimulation (tDCS) applied to the frontal or temporoparietal lobes has demonstrated potential to reduce the severity of ASD-related symptoms. Recently, the cerebellum has been identified as a brain area involved in ASD pathophysiology. In this open-label pilot study, seven ASD patients aged between 9 and 13 years underwent 20 daily sessions of 20 min cathodal stimulation of the right cerebellar lobe. At the end of the treatment, the Aberrant Behavior Checklist (ABC) scores showed a 25% mean reduction in global severity of symptoms, with a more pronounced reduction in the “social withdrawal and lethargy” (−35%), “hyperactivity and noncompliance” (−26%), and “irritability, agitation, and crying” (−25%) subscales. Minor and no improvement were observed in the “stereotypic behavior” (−18%) and “inappropriate speech” (−0%) subscales, respectively. Improvements were not detected in the two patients who were taking psychotropic drugs during the study. Clinical response showed a symptom-specific time course. Quality of sleep and mood improved earlier than hyperactivity and social withdrawal. The treatment was generally accepted by patients and well tolerated. No serious adverse events were reported. Stimulation also appeared to markedly reduce the severity of tics in a patient with comorbid tic disorder and led to the disappearance of a frontal epileptogenic focus in another patient with a history of seizures. In conclusion, cerebellar tDCS is safe, feasible, and potentially effective in the treatment of ASD symptoms among children. Strategies to improve recruitment and retention are discussed.

Natural recovery in trichotillomania

Objectives: Trichotillomania is characterized by repetitive pulling out of one’s hair, leading to distress and/or functional impairment. Long considered a chronic condition if left untreated (albeit with fluctuating intensity), there have been intimations that the disorder may be of limited duration in some people. Methods: A sample of 10,169 adults, aged 18–69 years, representative of the general US population, were recruited and screened for current and lifetime trichotillomania. Potential differences in demographic and clinical variables and lifetime comorbidities, between those with natural recovery from trichotillomania, and those with current trichotillomania, were identified using analysis of variance or likelihood-ratio chi-square tests as appropriate. Additional analyses using binary logistic regression were used to control for potential confounding differences between the groups initially identified. Results: In total, 24.9% of the entire sample of people with lifetime trichotillomania reported that they no longer had symptoms of trichotillomania and had never received therapy or medication treatment for it (i.e. they experienced natural recovery). Those who experienced natural recovery did not differ from those with current trichotillomania in terms of demographic or clinical characteristics, except that they were currently older. Natural recovery was associated with significantly lower rates of related comorbidities: obsessive-compulsive disorder, attention-deficit hyperactivity disorder, panic disorder, skin picking disorder and tic disorder. Discussion: These findings from the first epidemiology study examining natural recovery in trichotillomania highlight the importance of screening for and treating such comorbidities in patients with trichotillomania, in order to maximize chance of clinical recovery.

Tic Disorder of Children Analyzed and Diagnosed by Magnetic Resonance Imaging Features under Convolutional Neural Network

This work aimed to explore the analysis and diagnosis of children with tic disorder by magnetic resonance imaging (MRI) features under convolutional neural network (CNN), to provide a certain reference basis for clinical identification. A total of 45 children diagnosed with tic disorder in hospital from January 2018 to June 2020 were selected as the research subjects. A total of 30 normal children were selected as the control group. MRI images were collected, and CNN was constructed for image processing. The results showed that the convolutional neural network could significantly improve the speed of MRI reconstruction and can improve the diagnostic accuracy. Compared with normal children, the metabolites in children with tic disorder were slightly increased, but there was no statistical significance P > 0.05 . The results of the Yale score showed that the proportion of children with moderate illness was significantly greater than that of children with mild and severe illness. In short, the pathological changes of tic disorder were effectively discovered by MRI based on CNN algorithms, which can provide a reference for clinical identification.

Predicting Clinical Course from Subcortical Shape in Provisional Tic Disorder

The ongoing NewTics study examines children who have had tics for less than 9 months (NT group) - a population on which little research exists. Here, we further investigate relationships between subcortical shape and tic symptom outcomes. 138 children were assessed at baseline and a 12-month follow-up: 79 with NT, 27 tic-free healthy controls (HC), and 32 with chronic tic disorder or Tourette syndrome (TS), using T1-weighted MRI and total tic scores (TTS) from the Yale Global Tic Severity Scale to evaluate symptom change. Subcortical surface maps were generated using FreeSurfer-initialized large deformation diffeomorphic metric mapping, and linear regression models were constructed to correlate structural shapes with TTS while accounting for covariates, with relationships mapped onto structure surfaces. When compared to healthy controls, smaller mean volumes were found in the TS group for the caudate, nucleus accumbens, pallidum, and thalamus. NT had smaller mean volumes than controls in the caudate, pallidum, and thalamus. Surface maps illustrate distinct patterns of inward deformation (localized volume loss) in the TS group compared to NT children. In the NT group, a larger hippocampus at baseline significantly correlated with the worsening of tic symptoms at 12 months. Outward deformation in the hippocampus and inward deformation in the accumbens at baseline are also related to worsening tic symptoms at follow-up. Since the NT group has had tics only for a few months, we can rule out the possibility that these subcortical volume differences are caused by living with tics for years; they are more likely related to the cause of tics. These observations constitute some of the first prognostic biomarkers for tic disorders and suggest localized circuitry that may be associated with outcome of tic disorders.

Excessive Blinking in Children and Its Association with Dry Eyes and Visual Display Terminal: A 200 Case-Control Study

Objective: To identify the cause of excessive blinking in apparently healthy children, and to evaluate its association with visual activities including visual display terminal use. Material and Methods: The present study was a descriptive cross-sectional case-control study included 200 children aged 6 to 14 years with chief complaints of excessive blinking (study group) and routine eye check-up visits (control group). All participants underwent a complete eye examination including blink rate and tear break-up time measurement. Parents were asked to answer questionnaires regarding tic disorder and duration of visual activities. Results: One hundred children in the study group (mean age 7.9±2.0 years) and 100 children in the control group (mean age 9.5±2.3 years) were enrolled. Participants in the study group were predominantly male (77% versus 44%) and had a higher blink rate (30 versus 9 blinks/minute) compared to the control group. In the study group, there was a significantly higher percentage of participants diagnosed with dry eyes (73% versus 6%, p<0.001), allergic conjunctivitis (41% versus 0%, p<0.001) and tic disorder (19% versus 9%, p 0.042) than in the control group. One third of the participants in the study group had mixed diagnoses of dry eyes and allergic conjunctivitis. There was no significant difference in the duration of visual activities including visual display terminal use between groups. Conclusion: Excessive blinking occurred more commonly in boys. The most common associated disorders with excessive blinking in children were dry eyes, followed by allergic conjunctivitis and tic disorder. There was no association between excessive blinking in children and duration of visual display terminal use. Keywords: Blinking; Excessive blinking; Dry eyes; Visual display terminal