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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.

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.

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.

The Social Responsiveness Scale (SRS) is an autism rating scales in widespread use, with over 20 official foreign language translations. It has proven highly feasible for quantitative ascertainment of autistic social impairment in public health settings, however, little is known about the validity of the reinforcement in Asia populations or in references to DSM5. The current study aims to evaluate psychometric properties and cross-cultural aspects of the SRS-Korean version (K-SRS).The study subjects were ascertained from three samples: a general sample from 3 regular education elementary schools (n=790), a clinical sample (n=154) of 6-12-year-olds from four psychiatric clinics, and an epidemiological sample of children with ASD, diagnosed using both DSM IV PDD, DSM5 ASD and SCD criteria (n=151). Their parents completed the K-SRS and the Autism Spectrum Screening Questionnaire(ASSQ). Descriptive statistics, correlation analyses and principal components analysis (PCA) were performed on the total population. Mean total scores on the K-SRS differed significantly between the three samples. ASSQ scores were significantly correlated with the K-SRS T-scores. PCA suggested a one-factor solution for the total population.Our results indicate that the K-SRS exhibits adequate reliability and validity for measuring ASD symptoms in Korean children with DSM IV PDD and DSM5 ASD. Our findings further suggest that it is difficult to distinguish SCD from other child psychiatric conditions using the K-SRS.This is the first study to examine the relationship between the SRS subscales and DSM5-based clinical diagnoses. This study provides cross-cultural confirmation of the factor structure for ASD symptoms and traits measured by the SRS. Autism Res 2016, 9: 970-980. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

ObjectiveChanges in autism diagnostic criteria found in DSM-5 may affect autism spectrum disorder (ASD) prevalence, research findings, diagnostic processes, and eligibility for clinical and other services. Using our published, total-population Korean prevalence data, we compute DSM-5 ASD and social communication disorder (SCD) prevalence and compare them with DSM-IV pervasive developmental disorder (PDD) prevalence estimates. We also describe individuals previously diagnosed with DSM-IV PDD when diagnoses change with DSM-5 criteria.MethodThe target population was all children from 7 to 12 years of age in a South Korean community (N = 55,266), those in regular and special education schools, and a disability registry. We used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of screen-positive children were offered comprehensive assessments using standardized diagnostic procedures, including the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Best-estimate clinical diagnoses were made using DSM-IV PDD and DSM-5 ASD and SCD criteria.ResultsDSM-5 ASD estimated prevalence was 2.20% (95% confidence interval = 1.77-3.64). Combined DSM-5 ASD and SCD prevalence was virtually the same as DSM-IV PDD prevalence (2.64%). Most children with autistic disorder (99%), Asperger disorder (92%), and PDD-NOS (63%) met DSM-5 ASD criteria, whereas 1%, 8%, and 32%, respectively, met SCD criteria. All remaining children (2%) had other psychopathology, principally attention-deficit/hyperactivity disorder and anxiety disorder.ConclusionOur findings suggest that most individuals with a prior DSM-IV PDD meet DSM-5 diagnostic criteria for ASD and SCD. PDD, ASD or SCD; extant diagnostic criteria identify a large, clinically meaningful group of individuals and families who require evidence-based services.

Children with autism spectrum disorder (ASD) are frequently diagnosed with co‐occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random‐effects meta‐analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta‐regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle‐Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25–2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41–2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15–1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28–1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36–2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12–1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta‐regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD. Lay Summary: This systematic review and meta‐analysis of eight observational datasets found that individuals with autism spectrum disorder (ASD) are more likely to develop any inflammatory bowel disease, ulcerative colitis, or Crohn's disease. Our findings highlight the need to screen for inflammatory bowel disease in patients with ASD and elucidate the shared biological mechanisms between the two disorders. [ABSTRACT FROM AUTHOR]

The clinical heterogeneity of autism spectrum disorder (ASD) is closely associated with the diversity of genes related to ASD pathogenesis. With their low effect size, it has been hard to define the role of common variants of genes in ASD phenotype. In this study, we reviewed genetic results and clinical scores widely used for ASD diagnosis to investigate the role of genes in ASD phenotype considering their functions in molecular pathways. Genetic data from next-generation sequencing (NGS) were collected from 94 participants with ASD. We analyzed enrichment of cellular processes and gene ontology using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We compared clinical characteristics according to genetic functional characteristics. We found 266 genes containing nonsense, frame shift, missense, and splice site mutations. Results from DAVID revealed significant enrichment for "ion channel" with an enrichment score of 8.84. Moreover, ASD participants carrying mutations in ion channel-related genes showed higher total IQ (p = 0.013) and lower repetitive, restricted behavior (RRB)-related scores (p = 0.003) and mannerism subscale of social responsiveness scale scores, compared to other participants. Individuals with variants in ion channel genes showed lower RRB scores, suggesting that ion channel genes might be relatively less associated with RRB pathogenesis. These results contribute to understanding of the role of common variants in ASD and could be important in the development of precision medicine of ASD. [ABSTRACT FROM AUTHOR]

Abstract Background Previous evidence supports the role of noradrenergic systems in ADHD, and norepinephrine transporter (NET) is critical in regulating the noradrenergic system. The present study aimed to investigate the association between NET gene polymorphism and the performance measures of the Continuous Performance Test (CPT) in Korean ADHD children. Methods Eighty-seven children (mean age = 9.23 ± 1.99 years) with ADHD were recruited from a university hospital. Genotypes of G1287A of the NET gene (SLC6A2) were analyzed. All participants completed the CPT, with performance measures of omission errors, commission errors, reaction time and reaction standardization computed. The relationship between G1287A polymorphisms and CPT performance measures was examined. Results There were 46 subjects with the G/G genotype, 35 subjects with the G/A genotype and 6 subjects with the A/A genotype. Among the three groups, there were no significant differences in the performance of CPTs. When dichotomized according to whether the subjects have the rare allele or not, subjects with the homozygous G/G genotype showed significantly lower commission errors compared to those without G/G genotypes (by independent T-test, t = -2.18, p = 0.026). Discussion Our study found a significant association between commission errors of the CPT and the G1287A genotype of the NET gene in Korean ADHD children. These findings suggest a protective role of the G/G genotype of the NET polymorphisms in the deficits of response inhibition in ADHD children.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and restricted and repetitive behaviors and interests. Identifying the genetic background may be one of the key features for the future diagnosis and treatment of ASD. With the tremendous development in genetic diagnosis techniques, next-generation sequencing (NGS) can be used to analyze multiple genes simultaneously with a single test in laboratory and clinical settings and is well suited for investigating autism genetics. According to previous studies, there are two types of genetic variants in ASD, rare variants and common variants, and both are important in explaining pathogenesis. In this study, NGS data from 137 participants with ASD were reviewed retrospectively with consideration for comorbid epilepsy. Diagnostic yield was 17.51% (24/137), and pathogenic/likely pathogenic variants were seen more frequently in female participants. Fourteen participants were diagnosed with comorbid epilepsy, six of them had pathogenic/likely pathogenic variants (43%). Genes with variants of unknown significance (VOUS) which have one or more evidence of pathogenicity following the American College of Medical Genetics (ACMG) criteria were also reviewed in both ASD and ASD with comorbid epilepsy groups. We found that most frequently found VOUS genes have previously been reported as genes related to ASD or other developmental disorders. These results suggest that when interpreting the NGS results in the clinical setting, careful observation of VOUS with some pathological evidence might contribute to the discovery of genetic pathogenesis of neurodevelopmental disorders such as ASD and epilepsy. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and behavioral impairments. Recent studies have suggested that gut microbiota play a critical role in ASD pathogenesis. Herein, we investigated the fecal microflora of Korean ASD children to determine gut microbiota profiles associated with ASD. Specifically, fecal samples were obtained from 54 children with ASD and 38 age-matched children exhibiting typical development. Systematic bioinformatic analysis revealed that the composition of gut microbiota differed between ASD and typically developing children (TDC). Moreover, the total amounts of short-chain fatty acids, metabolites produced by bacteria, were increased in ASD children. At the phylum level, we found a significant decrease in the relative Bacteroidetes abundance of the ASD group, whereas Actinobacteria abundance was significantly increased. Furthermore, we found significantly lower Bacteroides levels and higher Bifidobacterium levels in the ASD group than in the TDC group at the genus level. Functional analysis of the microbiota in ASD children predicted that several pathways, including genetic information processing and amino acid metabolism, can be associated with ASD pathogenesis. Although more research is needed to determine whether the differences between ASD and TDC are actually related to ASD pathogenesis, these results provide further evidence of altered gut microbiota in children with ASD, possibly providing new perspectives on the diagnosis and therapeutic approaches for ASD patients. [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]

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]

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]

The definitions of "slow learners" and "borderline intellectual functioning (BIF)" have not reached a consensus and have continually evolved in terminology. The criteria for diagnosing BIF include the Full-Scale Intelligence Quotient, adaptive functioning, and onset of symptoms from the developmental period; however, specific standards have not been provided. Until the Diagnostic and Statistical Manual of Mental Disorders-IV, a range for the Full-Scale Intelligence Quotient was provided, but due to its limitations in reflecting the actual functioning of individuals with BIF, this criterion was removed from the Diagnostic and Statistical Manual of Mental Disorders-5. The absence of specific diagnostic criteria complicates the identification of individuals with BIF, highlighting the need for a more precise classification and definition., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Borderline intellectual functioning (BIF) is characterized by cognitive impairment and deficits in adaptive functioning. Despite affecting a significant proportion of the population, BIF still remains underdiagnosed and poorly understood. In addition to cognitive impairments across a range of domains, individuals with BIF face a greater risk of academic failure and often require special educational support. They suffer from emotional problems, such as difficulties with emotional awareness, anxiety, depressed mood, and unhappiness. Individuals with BIF are more likely to have an impairment of social and adaptive functioning. Furthermore, individuals with BIF are at higher risk of physical and mental health problems, often receive inadequate treatment, and have a poorer prognosis. This review aims to enhance the understanding of clinicians, educators, and policymakers by providing an overview of the characteristics of BIF and its associated challenges, ultimately contributing to the improvement of support systems for individuals with BIF., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Purpose: Numerous studies have supported the role of the immune dysfunction in the pathogenesis of autism spectrum disorder (ASD); however, to our knowledge, no study has been conducted on plasma cytokine levels in children with ASD in South Korea. In this study, we aimed to analyze the immunological characteristics of Korean children with ASD through plasma cytokine analysis., Materials and Methods: Blood samples were collected from 94 ASD children (mean age 7.1; 81 males and 13 females) and 48 typically developing children (TDC) (mean age 7.3; 30 males and 18 females). Plasma was isolated from 1 mL of blood by clarifying with centrifugation at 8000 rpm at 4℃ for 10 min. Cytokines in plasma were measured with LEGENDplex HU Th cytokine panel (BioLegend, 741028) and LEGENDplex HU cytokine panel 2 (BioLegend, 740102)., Results: Among 25 cytokines, innate immune cytokine [interleukin (IL)-33] was significantly decreased in ASD children compared with TDC. In acute phase proteins, tumor necrosis factor α (TNF-α) was significantly increased, while IL-6, another inflammation marker, was decreased in ASD children compared with TDC. The cytokines from T cell subsets, including interferon (IFN)-γ, IL-5, IL-13, and IL-17f, were significantly decreased in ASD children compared to TDC. IL-10, a major anti-inflammatory cytokine, and IL-9, which modulates immune cell growth and proliferation, were also significantly decreased in ASD children compared to TDC., Conclusion: We confirmed that Korean children with ASD showed altered immune function and unique cytokine expression patterns distinct from TDC., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Introduction: Previous studies have investigated predictive factors for parenting stress in caregivers of autism spectrum disorder (ASD) patients using traditional statistical approaches, but their study settings and results were inconsistent. Herein, this study aimed to identify major predictors for parenting stress in this population by developing explainable machine learning models., Methods: Study participants were collected from the Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, the Republic of Korea between March 2016 and October 2020. A total of 36 model features were used, which include subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) for caregivers' psychopathology, Social Responsiveness Scale-2 for core symptoms, and Child Behavior Checklist (CBCL) for behavioral problems. Machine learning classifiers [eXtreme Gradient Boosting (XGBoost), random forest (RF), logistic regression, and support vector machine (SVM) classifier] were generated to predict severe total parenting stress and its subscales (parental distress, parent-child dysfunctional interaction, and difficult child). Model performance was assessed by area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. We utilized the SHapley Additive exPlanations tree explainer to investigate major predictors., Results: A total of 496 participants were included [mean age of ASD patients 6.39 (SD 2.24); 413 men (83.3%)]. The best-performing models achieved an AUC of 0.831 (RF model; 95% CI 0.740-0.910) for parental distress, 0.814 (SVM model; 95% CI 0.720-0.896) for parent-child dysfunctional interaction, 0.813 (RF model; 95% CI 0.724-0.891) for difficult child, and 0.862 (RF model; 95% CI 0.783-0.930) for total parenting stress on the test set. For the total parenting stress, ASD patients' aggressive behavior and anxious/depressed, and caregivers' depression, social introversion, and psychasthenia were the top 5 leading predictors., Conclusion: By using explainable machine learning models (XGBoost and RF), we investigated major predictors for each subscale of the parenting stress index in caregivers of ASD patients. Identified predictors for parenting stress in this population might help alert clinicians whether a caregiver is at a high risk of experiencing severe parenting stress and if so, providing timely interventions, which could eventually improve the treatment outcome for ASD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Kim, Kim and Cheon.)