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Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients. Methods: To quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214). Results: In the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset. Conclusions: The application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity. [ABSTRACT FROM AUTHOR]

Background: Methylphenidate (MPH) blocks the norepinephrine transporter as well as the dopamine transporter. The α-2a-adrenergic receptor is a key component of the noradrenergic system. The aim of this study was to evaluate the association between the ADRA2A -1291 C>G polymorphism and the response to MPH treatment in Korean subjects with attention-deficit/hyperactivity disorder (ADHD). Methods: This study enrolled 114 ADHD children (mean age = 9.08 ± 1.94 years) from a child psychiatric clinic in South Korea. Subjects who had an improvement of ≥ 50% compared with the baseline ADHD rating scale (ARS) score or who had a Clinical Global Impression–improvement score of 1 or 2 points after treatment were defined as the “good response”. We examined the relationship of the ADRA2A to MPH response. Results: We found that a good response to MPH treatment, measured by the ARS as assessed by the parents, was observed for 76.9% of the subjects carrying the G/G genotype but for only 46.0% and 41.7% of those with the C/G and C/C genotypes, respectively [χ 2(2) = 11.929, p = .003]. We also found a significant difference in the change in total ARS scores between subjects with and without the G/G genotype [t(1) = 2.21, p = .029]. Conclusions: Our findings provide evidence of an association between the ADRA2A -1291 C>G genotype and response to MPH treatment in Korean subjects with ADHD. Nonetheless, the methodological limitation of not being a randomized placebo-controlled trial and primarily basing results on parent report to clinicians suggest that these results should be viewed as more preliminary. [Copyright &y& Elsevier]

Objective: The purpose of this study was to examine the clinical validities and efficiencies of the Child Behavior Checklist (CBCL) and the ADHD Rating Scale-IV (ARS) in identifying children with attention-deficit hyperactivity disorder (ADHD) in Korean community-based samples.Method: A large sample of elementary school students (n = 1668) participated in this study. We used the CBCL and the ARS as the screening instruments. Diagnoses were determined by clinical psychiatric interviews and confirmed by DSM-IV-based structured interviews.Results: Of the 46 subjects who underwent clinical psychiatric interviews, 33 were diagnosed as having ADHD. A T score of 60 with regard to the Attention Problems profile of the CBCL resulted in a reasonable level of sensitivity or positive predictive value in the diagnosis of ADHD. In both the parent and teacher reports of the ARS, 90th percentile cut-off points resulted in a high level of predictive value. The highest levels of specificity and positive predictive value were obtained when we combined the CBCL (T > or = 60 in Attention Problems) and the ARS (parent-teacher total > or = 90th percentile) reports.Conclusions: These findings suggest that the combined use of the CBCL and the ARS could serve as a rapid and useful clinical method of predicting or even diagnosing children with ADHD in epidemiologic case definitions. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4chlorophenyl) tropane ([[sup 123]I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction in children with ADHD. Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPET 2 h after the intravenous administration of [[sup 123]I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of ADHD symptoms in children with ADHD assessed with ADHD rating scale-IV and the specific/non-specific DAT binding ratio in the basal ganglia. Drug-naive children with ADHD showed a significantly increased specific/nonspecific DAT binding ratio in the basal ganglia compared with normal children. However, no significant correlation was found between the severity scores of ADHD symptoms in children with ADHD and the specific/nonspecific DAT binding ratio in the basal ganglia. Our findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD).Methods: A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism.Results: There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p < 0.001, p = 0.017).Conclusions: The results of this study do not support the association between the 5-HTTLPR polymorphism and treatment response with MPH in ADHD. However, our findings suggest the association between 5-HTTLPR polymorphism and the occurrence of tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting. [ABSTRACT FROM AUTHOR]

Children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID), need early intervention and continuous treatment. We aimed to investigate the feasibility and acceptability of mobile application-based interventions in children with ADHD and ID in supporting attention and cognitive function. Twenty-six children with ADHD and/or ID with attention and cognition difficulties were recruited. Participants completed a 12-week mobile application-based intervention. To assess whether digital intervention improved attention and cognitive function, we used the Comprehensive Attention Test (CAT), Cambridge Neuropsychological Tests Automated Battery (CANTAB), and electroencephalography (EEG) to examine direct changes in children's behavior and neural activity. Clinicians and parents assessed changes using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Korean version of the ADHD Rating Scale (K-ARS), Clinical Global Impression-Improvement Scale, and parental questionnaires. The intervention induced changes in neural activities on EEG and behavior but there were no significant changes in CAT and CANTAB results. Relative theta and alpha power were significantly lower post-intervention in the eyes-open (EO) condition of EEG recording and these changes were mainly observed in the frontal regions of the brain. Parental reports using the BRIEF-2 and K-ARS noted significant improvements in executive function, attention, and hyperactivity-impulsivity. In addition, the clinical impression improved in 60% of participants. These results provide evidence that a mobile application-based intervention has the benefit of supporting children with ADHD and/or ID. Digital intervention could change neural activity and improve children's attention and cognitive function. Given our findings, we suggested that mobile application-based digital therapeutics may have great potential for helping children with neurodevelopmental disorders who need continuous treatment. [ABSTRACT FROM AUTHOR]

Objectives: Although tic disorder (TD) is a common mental disorder in children and adolescents, epidemiological data based on real-world evidence (RWE) are insufficient. Using RWE, this study sought to examine the prevalence of treated TD, use of medical utilization, and use of prescription drugs among patients with TD with respect to TD type and comorbid psychiatric illness. Methods: We performed a retrospective cross-sectional study. Using the Korean Health Insurance Review and Assessment Service Pediatric Patient Sample data from 2009 to 2016, we analyzed 20,599 patients with TD (Korean Standard Classification of Diseases-6/7 code: F95.x) aged 2-19 years. Results: The annual average TD prevalence was 2.6/1000 population (95% confidence interval, 2.3-2.8/1000). Between 2009 and 2016, a slight increase in TD prevalence was observed from 1.9 to 2.9/1000 population. The TD prevalence rate in male patients was four times higher than that in female patients. Differences were observed in health care utilization and drug prescription types between patients with Tourette syndrome and chronic or transient TD. In addition, more than half of patients with TD had comorbid psychiatric disorders, and one-third of patients with TD had attention-deficit/hyperactivity disorder (ADHD). Patients with TD without comorbidities were frequently prescribed aripiprazole, while patients with TD and comorbid ADHD were frequently prescribed atomoxetine, methylphenidate, risperidone, and aripiprazole. Conclusion: This study described the epidemiological characteristics of TD based on recent RWE from Korea, and its findings can help establish future TD evidence-based clinical guidelines and related policies. [ABSTRACT FROM AUTHOR]

Abstract: Although the etiology of Attention Deficit/Hyperactivity Disorder (ADHD) is not well understood, evidence from the family and twin studies suggest that ADHD is familial and highly heritable. The aim of the study was to test whether dopamine transporter gene (DAT1) and dopamine receptor D4 gene (DRD4) polymorphisms are in linkage disequilibrium with ADHD in Korean children, using a family-based association study. One hundred and twenty-six trios were studied and 87% of probands were boys (mean age=8.2 years, mean IQ=104). ADHD not otherwise specified (NOS) was the most common subtype and comorbidity rates were low. Descriptive analysis and the TDT test were the primary analyses. In exploratory analyses, logistic regression and QTDT were performed. The 10-repeat allele and 4-repeat allele were the most frequent for DAT1 and DRD4. TDT test for DAT1 and DRD4 did not show preferential transmission. Based on logistic regression and QTDT, the 5-repeat allele of DRD4 may confer protection for hyperactive-impulsivity symptom severity compared to the 4-repeat allele. The negative TDT finding between DAT1 and DRD4 VNTR polymorphisms and ADHD should be interpreted with caution; partly due to lack of power caused by low heterozygosity in the study population. Future studies are necessary to test the hypothesis generated in this study that the 5-repeat allele of DRD4 is protective for hyperactive-impulsivity symptom severity compared to the 4-repeat allele. [Copyright &y& Elsevier]