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Abstract: Background: Autism has been hypothesized to reflect neuronal disconnection. Several recent reports implicate the key thalamic relay nuclei and cortico-thalamic connectivity in the pathophysiology of autism. Accordingly, we aimed to focus on evaluating the integrity of the thalamic radiation and sought to replicate prior white matter findings in Korean boys with high-functioning autism spectrum disorders (ASD) using Diffusion Tensor Imaging (DTI). Methods: We compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in 17 boys with ASD and 17 typically developing controls in the anterior thalamic radiation (ATR), superior thalamic radiation (STR), posterior thalamic radiation (PTR), corpus callosum (CC), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Results: The two groups were group-matched on age, IQ, handedness and head circumference. In whole-brain voxel-wise analyses, FA was significantly reduced and MD was significantly increased in the right ATR, CC, and left UF in subjects with ASD (p<0.05, corrected). We found significantly lower FA in right and left ATR, CC, left UF and right and left ILF and significantly higher MD values of the CC in the ASD group in region of interest-based analyses. We also observed significantly higher RD values of right and left ATR, CC, left UF, left ILF in subjects with ASD compared to typically developing boys and significantly lower AD values of both ILF. Right ATR and right UF FA was significantly negatively correlated with total SRS score within the ASD group (r=−.56, p=.02). Conclusions: Our preliminary findings support evidence implicating disturbances in the thalamo-frontal connections in autism. These findings highlight the role of hypoconnectivity between the frontal cortex and thalamus in ASD. [Copyright &y& Elsevier]

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]

Abstract: The studies on the genetic risk factors of the children of alcoholics (COAs) are still in an early stage. The A1 allele of the dopamine receptor 2 gene (DRD2) may be associated with positive alcohol expectancy of the COAs. In addition, several researchers reported that the COAs might be associated with the GABAA receptor β3 subunit gene (GABRB3) and serotonin transporter gene (5-HTTLPR). In this study, we investigated the association of the polymorphism of the DRD2, Dopamine D4 receptor gene (DRD4), GABRB3, 5-HTTLPR with the COAs. Twenty-two COAs and 23 age and sex-matched control children were included for the genetic study (children of nonAlcoholics; nonCOAs). All COAs aged 6–18 were recruited and selected from family of alcoholic patients in Alcohol Clinic of the University hospital. The genotyping of the DRD2, DRD4, GABRB3, 5-HTTLPR was carried out. We used the Chi-square method for evaluating the association of genetic polymorphic allelic status with the COAs. The frequency of the A1+ allele at DRD2 in the COAs was significantly higher than nonCOAs. Significant association between the genotype at DRD4 and the COAs was found. The G1− alleles of the GABRB3 in COAs were significantly higher than nonCOAs. However, no association of the polymorphic alleles of the 5-HTTLPR with the COAs was found. We found that the children of alcoholics had a significantly increased number of risk alleles of candidate genes of alcohol drinking expectancy. Despite of several limitations, this study provides some preliminary information on the risk and protective factors associated with the COAs, which can be used as a foundation for prevention and intervention of future psychopathology. [Copyright &y& Elsevier]

Abstract: The symptoms of attention deficit hyperactivity disorder (ADHD) can be treated with methylphenidate (MPH), a potent blocker of dopamine transporter (DAT). The homozygosity of the 10-repeat allele at the DAT gene (DAT1) seems to be associated with a poor response to MPH in children with ADHD. In the present study, we investigated the association between DAT density using I-123-N-(3-iodopropen-2-yl)-2β-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT single photon emission computed tomography (SPECT)] and the homozygosity for 10-repeat allele at DAT1 and response to MPH in Korean children with ADHD. Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks. After the genotyping and SPECT were performed, we compared DAT density between ADHD children with and without the homozygosity for 10-repeat allele at DAT1 and investigated the correlation between the homozygosity for 10-repeat allele and response to MPH. ADHD children with 10/10 genotype (n=7) had a significantly greater increase of the DAT density in basal ganglia than the children without 10/10 genotype (n=4). We found that while only 28.6% (2/7) of the subject with 10/10 genotype showed good response to MPH treatment, 100% (4/4) of the subjects without 10/10 genotype showed good response to MPH treatment. Our findings support an association between homozygosity for 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for 10-repeat allele and poor response to MPH. [Copyright &y& Elsevier]

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]

Children and adolescents with autism spectrum disorder (ASD) experience various sleep problems. Sleep problems co-occur in a bidirectional relationship with ASD core symptoms and behavioral problems. However, studies on how these three factors are intricately linked to each other are limited. This meta-analysis examined the differential relationship between specific sleep problems, core symptoms, and behavioral problems in this population. This study was registered in PROSPERO (CRD42022339695). We systematically searched the PubMed/MEDLINE, Web of Science, and Scopus databases from inception to April 27, 2022. Observational studies that reported correlations between measures of sleep problems, ASD core symptoms, or ASD behavioral problems were included, and participants aged 18 years or below were enrolled. The correlation coefficient (r) was assessed as the primary effect metric. Total 22 cross-sectional studies were included, which comprised 2655 participants (mean age = 6.60 years old; mean percentage of boys = 80.64%). We found correlations between total sleep problems and total core symptoms (r 0.293 [95% confidence interval − 0.095 to 0.604]), total sleep problems and total behavioral problems (r 0.429 [0.299–0.544]), and total core symptoms and total behavioral problems (r − 0.050 [− 0.177 to 0.079]) and identified statistically significant correlations between specific components of sleep problems, ASD core symptoms, and ASD behavioral problems. Each specific sleep problem showed a unique association with core symptoms and behavioral problems. Sleep problems in ASD should be explored in detail, and the closely linked core symptoms and behavioral problems should be common therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. Methods: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. Results: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g − 0.857, 95% CI − 1.263 to − 0.451, certainty of evidence: high) and aripiprazole (Hedges' g − 0.559, 95% CI − 0.767 to − 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g − 0.893, 95% CI − 1.184 to − 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. Limitations: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. Conclusions: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965. [ABSTRACT FROM AUTHOR]

Children and adolescents with Autism Spectrum Disorder (ASD) are characterized by an impaired Theory of Mind (ToM). Recent evidence suggested that two aspects of ToM (cognitive ToM versus affective ToM) are differentially impaired in individuals with ASD. In this study, we examined the neural correlates of cognitive and affective ToM in children and adolescents with ASD compared to typically developing children (TDCs). Twelve children and adolescents with ASD and 12 age, IQ matched TDCs participated in this functional MRI study. The ToM task involved the attribution of cognitive and affective mental states to a cartoon character based on verbal and eye-gaze cues. In cognitive ToM tasks, ASD participants recruited the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and superior temporal gyrus (STG) to a greater extent than did TDCs. In affective ToM tasks, both ASD and TDC participants showed more activation in the insula and other subcortical regions than in cognitive ToM tasks. Correlational analysis revealed that greater activation of the mPFC/ACC regions was associated with less symptom severity in ASD patients. In sum, our study suggests that the recruitment of additional prefrontal resources can compensate for the successful behavioral performance in the ToM task in ASD participants. [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]

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]

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]

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies. [ABSTRACT FROM AUTHOR]

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]

It has been suggested that dopamine, as well as serotonin, is associated with the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies have been performed on brain regions associated with dopamine in patients with OCD. In the present study, we investigated the DAT density of the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane ([123I]IPT) single-photon emission tomography (SPET) and evaluated the activity of the presynaptic dopamine function in patients with OCD. Fifteen patients with OCD and 19 normal control adults were included in the study. We performed brain SPET 2 h after the intravenous administration of [123I]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 dopamine transporter (DAT) binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia. Compared with normal control adults, patients with OCD showed a significantly increased specific/non-specific DAT binding ratio in the right basal ganglia and a tendency towards an increased specific/non-specific DAT binding ratio in the left basal ganglia. No significant correlation was found between the total scores on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia in patients with OCD could be involved in the pathophysiology of OCD. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate changes of diagnoses, PTSD-related scales, and social support scale in child and adolescent victims with sexual abuse based on the cohorts of Nation-funded Childhood Sexual Abuse (CSA) protection center in Korea. Eighteen of 22 subjects had diagnoses of mental illness, such as PTSD with/without depressive disorder, depressive disorder, adjustment disorder, and enuresis. Our data suggest that the prevalence of mental illness would be decreased, and the scores of PTSD-related and behavioral problems and familial functioning for CSA victims would be improved at the 1-year follow-up period. [Extracted from the article]

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]

Tourette's disorder (TD) is characterized by multiple motor and one or more vocal tics. We retrospectively assessed the clinical outcomes of 8 patients with refractory TD who underwent DBS. All patients reported improvement in tic severity at 3 months after surgery, and mean YGTSS severity score was 32.38 (SD = 10.53; p = 0.012). [Extracted from the article]

Aim: Data pertaining to child and adolescent psychiatry (CAP) training systems are limited as extant research has mostly been derived from one‐time data collection. This 5‐year follow‐up survey collects updated information on CAP training systems in the Far East, allowing for the tracking of system changes over the past 5 years. Methods: Data were obtained from 18 countries, or functionally self‐governing areas, in the Far East, 17 of which were also included in the original study. An online questionnaire was completed by leading CAP professionals in each country. Questions were expanded in the present study to capture the contents of CAP training. Results: When compared to data from the original study, there has been progress in CAP training systems in the last 5 years. Specifically, there has been an increase in the number of countries with CAP training programs and national guidelines for the training. In addition, the number of CAP departments/divisions affiliated with academic institutions/universities has increased. Findings from 12 of 18 countries in the present study provide data on clinical contents. All informants of the present study reported the need for more child and adolescent psychiatrists and allied professionals. Conclusion: Despite progress in CAP training systems over the last 5 years, the need for more professionals in child and adolescent mental health care in all the relevant areas in this region have yet to be adequately addressed. Continued national efforts and international collaborations are imperative to developing and sustaining new CAP training systems while facilitating improvements in existing programs. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

The current treatment of choice for attention deficit hyperactivity disorder (ADHD) is pharmacotherapy. A search for new treatment options is underway, however, as the wide application of drugs to the general population of patients with ADHD is limited by side effects and the variance of pharmacokinetic effects of the drugs in each patient. In the present study, we applied repetitive transcranial magnetic stimulation (rTMS), a non-invasive treatment used in a number of other psychiatric disorders, to spontaneously hypertensive rats (SHRs), an animal model of ADHD, in order to assess the efficacy of the treatment in modifying behavioural symptoms as well as levels of dopamine, noradrenaline, serotonin, and brain-derived neurotrophic factor (BDNF). A total of fifteen sessions of high-frequency rTMS treatment were administered. Behavioural symptoms were observed using open field, Y-maze, and elevated plus-maze tests. Upon completion of the experiments, rats were sacrificed, and the neurochemical changes in brain tissue were analysed using high performance liquid chromatography and Western blotting. The SHRs treated with rTMS tended to exhibit less locomotor activity in the open field test over the course of treatment, but there was no improvement in inattention as measured by the Y-maze test. Furthermore, BDNF concentration increased and noradrenaline concentration decreased in the prefrontal cortex of SHRs treated with rTMS. The results of the present preclinical study indicate that rTMS may constitute a new modality of treatment for patients with ADHD, through further evaluation of specific treatment parameters as well as safety and efficacy in humans are required. [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]

An abstract of the article "Behavior Assessment System for Children-2, Parent Rating Scale-Chidren As a Potential Screener for Autism Spectrum Disorder in Korean Children" by Jungeun Song and colleagues is presented.