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The authors aimed to study the effects of postnatal exposure to phthalate on anxiety-like behavior in mice and anxiety proneness in children. Male Imprinting Control Region (ICR) mice aged 4 weeks were administered 20 to 540 mg/kg of di-(2-ethylhexyl) phthalate (DEHP) or vehicle and assessed in the Open Field Test. A group of 277 children aged 8-11 years (150 males) was recruited from South Korea. A cross-sectional examination of urinary DEHP and dibutylphthalate metabolite concentrations was conducted, and the children were scored on the Trait Anxiety Inventory for Children (TAIC). DEHP metabolite concentrations in the urine were significantly and negatively correlated with TAIC scores in the female population but not in the male population. There were no significant group differences in the percentage of distance moved or time spent in the central area in male mice treated with DEHP or vehicle. Our results suggest a sex-dependent effect of DEHP on anxiety proneness in childhood. [ABSTRACT FROM AUTHOR]

We compared executive functions (EFs) of traumatized preadolescent children with and without marked posttraumatic stress disorder (PTSD) symptoms to the performance of a nontraumatized control group, and examined the relationships between EF deficits and functional status in traumatized preadolescent children. Fifty-one preadolescent children who had witnessed a death at school 30 months prior (26 with marked PTSD symptoms and 25 without) and 30 healthy controls who had not been traumatized participated. EFs were examined using the Comprehensive Attention Test (CAT). The functional state of traumatized children was measured by the Parent Report Form-Children's Health and Illness Profile-Children's Edition (PRF-CHIP-CE). The traumatized children, regardless of status of PTSD symptomatology, showed poorer working memory performance than nontraumatized healthy controls. The traumatized children with marked PTSD symptoms performed more poorly on measures of interference control compared to those children without marked PTSD symptoms. Lower levels of EFs were associated with lower risk avoidance and diminished academic achievement in traumatized children. These results indicate that an inhibitory control deficit is specifically associated with the current PTSD symptoms but not with trauma exposure per se. [ABSTRACT FROM PUBLISHER]

Impaired social functioning is a hallmark feature of autism spectrum disorder ( ASD), often requiring treatment throughout the life span. PEERS® ( Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS® has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS® for enhancing social skills through a randomized controlled trial ( RCT).The English version of the PEERS® Treatment Manual ( Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient ( IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group ( TG) or delayed treatment control group ( CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS® treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms ( p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale ( p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge- Revised ( p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment ( p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables ( p < 0.05). Despite cultural and linguistic differences, the PEERS® social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS® treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD. Autism Res 2014, 7: 145-161. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Monoamine oxidase A gene (MAOA) has been thought to be a candidate gene implicated in autism spectrum disorder (ASD). This study evaluates the relationship between ASDs and MAOA markers (i.e., uVNTR and four single nucleotide polymorphisms (SNPs)) in 151 Korean family trios with children diagnosed with ASDs, and 193 unrelated Korean controls. The result of case–control global haplotype analysis also showed a statistically significant difference in haplotype frequencies between ASD patients and controls (male d.f.=5, p <0.001; female d.f.=7, p <0.001). With the specific haplotype analyses, the frequencies of the most frequent haplotype (AGG) with three SNPs (rs5906883+rs1137070+rs3027407) in ASD showed significant statistical differences between ASD patients and controls in both the male and female groups (d.f.=1, male p =0.001, female p <0.001). In a family-based association test (FBAT) analysis, it was observed that, in the dominant model, a three-repeat allele of a MAOA-uVNTR marker was preferentially transmitted in ASDs (Z =2.213, p =0.027). Moreover, in the global haplotype analysis, the statistically significant evidence of associations with ASD were demonstrated in additive and dominant models (additive χ 2 =11.349, d.f.=2, p =0.003; dominant χ 2 =6.198, d.f.=2, p =0.045). [Copyright &y& Elsevier]

Autism spectrum disorder (ASD) is a highly heritable condition caused by a combination of environmental and genetic factors such as de novo and inherited variants, as well as rare or common variants among hundreds of related genes. Previous genome-wide association studies have identified susceptibility genes; however, most ASD-associated genes remain undiscovered. This study aimed to examine rare de novo variants to identify genetic risk factors of ASD using whole exome sequencing (WES), functional characterization, and genetic network analyses of identified variants using Korean familial dataset. We recruited children with ASD and their biological parents. The clinical best estimate diagnosis of ASD was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5TM), using comprehensive diagnostic instruments. The final analyses included a total of 151 individuals from 51 families. Variants were identified and filtered using the GATK Best Practices for bioinformatics analysis, followed by genome alignments and annotation to the reference genome assembly GRCh37 (liftover to GRCh38), and further annotated using dbSNP 154 build databases. To evaluate allele frequencies of de novo variants, we used the dbSNP, gnomAD exome v2.1.1, and genome v3.0. We used Ingenuity Pathway Analysis (IPA, Qiagen) software to construct networks using all identified de novo variants with known autism-related genes to find probable relationships. We identified 36 de novo variants with potential relations to ASD; 27 missense, two silent, one nonsense, one splice region, one splice site, one 5′ UTR, and one intronic SNV and two frameshift deletions. We identified six networks with functional relationships. Among the interactions between de novo variants, the IPA assay found that the NF-κB signaling pathway and its interacting genes were commonly observed at two networks. The relatively small cohort size may affect the results of novel ASD genes with de novo variants described in our findings. We did not conduct functional experiments in this study. Because of the diversity and heterogeneity of ASD, the primary purpose of this study was to investigate probable causative relationships between novel de novo variants and known autism genes. Additionally, we based functional relationships with known genes on network analysis rather than on statistical analysis. We identified new variants that may underlie genetic factors contributing to ASD in Korean families using WES and genetic network analyses. We observed novel de novo variants that might be functionally linked to ASD, of which the variants interact with six genetic networks. [ABSTRACT FROM AUTHOR]

The present study reports past-year prevalence of and comorbidities associated with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) disorders in 1645 children aged 6 to 12 years in Seoul, Korea. The diagnosis was based on the parental version of the Diagnostic Interview Schedule for Children (DISC-IV). Our participants completed the Children’s Depression Inventory (CDI). The estimated prevalence of any full-syndrome and subthreshold DSM-IV disorders were 16.2% and 28.1%, respectively. The most prevalent disorders were specific phobia (9.6%), attention-deficit hyperactivity disorder (ADHD; 5.9%), and oppositional defiant disorder (ODD; 4.9%). The estimated prevalence of depressive disorder was 0.1% according to the DISC-IV and1.9% according to the CDI. ADHD, ODD, and anxiety disorders were highly comorbid. Our study highlights the importance of obtaining children’s self-report data in addition to the parents’ interview, particularly for depression, and the importance of early detection of subthreshold conditions and considering comorbid diagnoses. [ABSTRACT FROM PUBLISHER]

Background: Although the Korean version of the Autism Diagnostic Observation Schedule-2 (K-ADOS‐2) is widely being used to diagnose autism spectrum disorder (ASD) in South Korea, no previous study has examined the validity and reliability of all modules of K-ADOS-2 across a wide age range, particularly older children, adolescents, and adults. Method: Data from 2,158 participants were included (mean age = 79.7 months; 73.6% male): 1473 participants with ASD and 685 participants without ASD (Toddler Module, n = 289; Module 1, n = 642; Module 2 n = 574; Module 3 n = 411; Module 4, n = 242). Participants completed a battery of tests, including the K-ADOS or K-ADOS-2 and other existing diagnostic instruments. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, positive predictive value (PPV), negative predictive value (NPV), Cohen's kappa (k), and agreement with existing diagnostic instruments were computed. Cronbach's α values were also calculated. Results: All developmental cells of the K-ADOS-2 showed sufficient ranges of sensitivity 85.4–100.0%; specificity, 80.4–96.8%; area under the ROC curve,.90-.97; PPV, 77.8–99.3%; NPV, 80.6–100.0%; and k values,.83–.92. The kappa agreements of developmental cells with existing diagnostic instruments ranged from.20 to.90. Cronbach's α values ranged from.82 to.91 across all developmental cells. Limitation: The best-estimate clinical diagnoses made in this study were not independent of the K-ADOS-2 scores. Some modules did not include balanced numbers of participants in terms of gender and diagnostic status. Conclusion: The K-ADOS-2 is a valid and reliable instrument in diagnosing ASD in South Korea. Future studies exploring the effectiveness of the K-ADOS-2 in capturing restricted, repetitive behaviors and differentiating ASD from other developmental disabilities are needed. [ABSTRACT FROM AUTHOR]

Background: The psychiatric treatment gap is substantial in Korea, implying barriers in seeking help. Objectives: This study aims to explore barriers of seeing psychiatrists, expressed on the internet by age groups. Methods: A corpus of data was garnered extensively from internet communities, blogs and social network services from 1 January 2016 to 31 July 2019. Among the texts collected, texts containing words linked to psychiatry were selected. Then the corpus was dismantled into words by using natural language processing. Words linked to barriers to seeking help were identified and classified. Then the words from web communities that we were able to identify the age groups were additionally organized by age groups. Results: 97,730,360 articles were identified and 6,097,369 were included in the analysis. Words implying the barriers were selected and classified into four groups of structural discrimination, public prejudice, low accessibility, and adverse drug effects. Structural discrimination was the greatest barrier occupying 34%, followed by public prejudice (27.8%), adverse drug effects (18.6%), and cost/low accessibility (16.1%). In the analysis by age groups, structural discrimination caused teenagers (51%), job seekers (64%) and mothers with children (43%) the most concern. In contrast, the public prejudice (49%) was the greatest barriers in the senior group. Conclusions: Although structural discrimination may most contribute to barriers to visiting psychiatrists in Korea, variation by generations may exist. Along with the general attempt to tackle the discrimination, customized approach might be needed. [ABSTRACT FROM AUTHOR]

This study aimed to pilot PAX ("Play, Act & Interact"), an activity-based emotional support intervention for caregivers of child with cancer, which focuses on addressing their psychological distress and post-traumatic stress symptoms (PTSSs). Sixteen mothers whose children were child with cancer participated in this 4-week intervention. Their children (n = 16; 14 males; median age at diagnosis = 10.3 years; the median amount of time from diagnosis = 9 months) were at different treatment stages for a range of different diagnoses. Caregivers completed self-report instruments assessing their psychological distress including PTSSs and family functioning before and after the intervention and a brief open-response exit survey. Paired sample t-tests were computed to compare the pre-and post-intervention scores. The Post-traumatic Stress Disorder Checklist scores significantly decreased from pre- (M = 37.00, SD = 14.75) to post-intervention (M = 32.56, SD = 15.52), t(15) = 4.25, p <.001. There was also a significant difference between pre- (M = 33.5, SD = 3.18) and post-intervention (M = 35.7, SD = 3.14) scores on the Family Adherence subscale of the Family Adaptability and Cohesion Evaluation Scales III, t(15) = −2.58, p =.02. PAX was a promising intervention for supporting caregivers' PTSSs and family adaptability. Future studies investigating the long-term effects and replicating the current study with more participants and a control group are needed. [ABSTRACT FROM AUTHOR]

Few studies have investigated the effect of age on treatment effectiveness of evidence-based social skills training in autism spectrum disorder (ASD) adolescents. This study evaluated the effectiveness of Program for the Education and Enrichment of Relational Skills (PEERS®) in different ages of ASD adolescents. A total of 110 ASD adolescents aged 11–19 years were divided into early, middle, and late adolescence groups, and the changes in outcome measures following intervention were compared among the three groups. We found that the improvements in social competence after PEERS® were significant, but the treatment effects were not significantly different among the three age groups. The findings suggest that PEERS® is beneficial for ASD adolescents regardless of patient age and adolescence stage. [ABSTRACT FROM AUTHOR]

Background: Low-level environmental exposure to lead has been associated with both reduced intelligence and symptoms of attention deficit/hyperactivity disorder (ADHD). However, few studies have estimated the association of lead and intelligence independent of ADHD, and it is not clear from previous studies whether lead is associated with both inattention and impulsivity ADHD symptoms. Objectives: We estimated mutually adjusted associations of environmental lead exposure with both intelligence and ADHD symptoms, and associations between lead and specific ADHD-related domains. Methods: Blood lead concentrations were measured in a general population of 1,001 children 8–11 years of age. We used multivariable linear regression models to estimate associations of blood lead concentrations with IQ scores, teacher and parent ratings of ADHD symptoms, and measures of inattention and impulsivity. Models were adjusted for demographic variables and other environmental exposures (blood levels of mercury and manganese, urinary concentrations of cotinine, phthalate metabolites, and bisphenol A). Results: Associations of blood lead with lower IQ and higher impulsivity were robust to adjustment for a variety of covariates. When adjusted for demographic characteristics, other environmental exposures, and ADHD symptoms or IQ, a 10-fold increase in blood lead concentration was associated with lower Full-Scale IQ (–7.23; 95% CI: –13.39, –1.07) and higher parent- and teacher-rated hyperactivity/impulsivity scores (ADHD Rating Scale, 1.99; 95% CI: 0.17, 3.81 and 3.66; 95% CI: 1.18, 6.13, respectively) and commission errors (Continuous Performance Test, 12.27; 95% CI: –0.08, 24.62). Blood lead was not significantly associated with inattention in adjusted models. Conclusions: Low-level lead exposure was adversely associated with intelligence in school-age children independent of ADHD, and environmental lead exposure was selectively associated with impulsivity among the clinical features of ADHD. [ABSTRACT FROM AUTHOR]

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8–11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions. [ABSTRACT FROM AUTHOR]

Background We investigated the distinct longitudinal trajectories of posttraumatic stress symptoms in a sample of 167 children, who witnessed death of two mothers of their schoolmates. Methods The cohort was followed-up at 2 days (T1), 2 months (T2), 6 months (T3), and 30 months (T4) after the traumatic event. The children's posttraumatic stress symptoms (T1-T4), depression (T1, T3 and T4), state anxiety (T1, T3 and T4), and quality of life (T4) were assessed, along with parental stress related to child rearing (T4). Different trajectory patterns of the children's posttraumatic stress symptoms were identified using growth mixture modeling ( GMM). Results Four different patterns of symptom change were identified, which were consistent with the prototypical model, and were named Recovery (19.9%), Resilience (72.7%), Chronic Dysfunction (1.8%), and Delayed Reactions (5.6%). Significant differences were found in depression and anxiety scores, children's quality of life, and parental rearing stress according to the distinct longitudinal trajectories of posttraumatic stress symptoms. Conclusions The present study suggests that individual differences should be taken into account in the clinical course and outcome of children exposed to psychological trauma. The two most common trajectories were the Resilience and the Recovery types, together suggesting that over 90% of children were evidenced with a favorable 30-month outcome. The latent classes were associated with significant mean differences in depression and anxiety scores, supporting the clinical validity of the distinct trajectories. [ABSTRACT FROM AUTHOR]

Background: Evidence supporting a link between postnatal environmental tobacco smoke (ETS) exposure and cognitive problems among children is mounting, but inconsistent. Objectives: We examined the relationship between ETS exposure, measured using urine cotinine, and IQ scores in Korean school-aged children. Methods: The participants were 996 children 8–11 years of age recruited from five administrative regions in South Korea. We performed a cross-sectional analysis of urinary cotinine concentrations and IQ scores obtained using the abbreviated form of a Korean version of the Wechsler Intelligence Scales for Children. Associations were adjusted for potential confounders, and estimates were derived with and without adjustment for mother’s Full-Scale IQ (FSIQ) score. Results: After adjusting for sociodemographic and developmental covariates, urinary cotinine concentrations were inversely associated with FSIQ, Verbal IQ (VIQ), Performance IQ (PIQ), vocabulary, math, and block design scores. Following further adjustment for maternal IQ, only the VIQ scores remained significantly associated with urinary cotinine concentration (B = –0.31; 95% CI: –0.60, –0.03 for a 1-unit increase in natural log-transformed urine cotinine concentration; p = 0.03). Conclusion: Urine cotinine concentrations were inversely associated with children’s VIQ scores before and after adjusting for maternal IQ. Further prospective studies with serial measurements of cotinine are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

This study compared children who experience attention-deficit/hyperactivity disorder (ADHD) symptoms but do not meet criteria (i.e., subthreshold ADHD) with those with the full syndrome and healthy controls. Presence of ADHD symptoms was determined in a nationwide community sample of 921 children, aged 8-11 years. The main outcome measures comprised attentional symptoms, comorbidity profiles, academic performance, and neurocognitive ability (i.e., ADHD Rating Scale, Child Behavior Checklist, Learning Disability Evaluation Scale, and Stroop Color-Word Test, respectively). Subthreshold ADHD was equally prevalent in boys and girls, and more prevalent in low-income families. Throughout all the outcome measurements, subthreshold ADHD was both a significantly milder condition than full syndrome ADHD and a significantly more severe condition than non-ADHD status. The findings were consistent across the total as well as the subtest scores, and after correction for multiple comparisons ( p < 0.0017). Children with subthreshold ADHD were found to experience significant symptoms and functional impairments. The results of this study support the clinical relevance of subthreshold ADHD in a childhood population. Subthreshold diagnostic criteria for ADHD may be more sensitive in detecting ADHD symptoms in girls than the full syndrome criteria, and subthreshold clinical, cognitive, and behavioral symptoms of ADHD may occur in a subset of children who are possibly more sensitive to their environment. Further consideration about the diagnostic threshold for ADHD may particularly benefit girls and children in low-income families. [ABSTRACT FROM AUTHOR]

Background The lethality of the suicide method is a strong risk factor for completed suicide. We examined whether the annual change in the pattern of suicide methods was related to the annual change in suicide rates among adolescents in South Korea and the United States. Methods We analyzed annual data for the 2000-2009 period for South Korea and the 2000-2008 period for the United States to examine time trends in the suicide rates and suicide methods of adolescents aged 10-19 years in two countries. Data on suicide methods were obtained from the World Health Organization ( WHO) mortality database. Results Suicide rates among adolescents in the United States have remained relatively steady since 2000, whereas the suicide among Korean adolescents has increased. Between 2000 and 2009, the most common suicide method among Korean adolescents was jumping for boys and girls, whereas it was hanging for girls and firearms for boys in the United States. Along with the annual increase in suicide rates in South Korea, the incidences of jumping among males and hanging (and recently jumping) among females have increased steadily, whereas suicide by self-poisoning steadily decreased. In the United States, between 2000 and 2008, the proportion of suicides committed by hanging increased, whereas those committed using firearms steadily decreased, particularly among adolescent females. Conclusions These findings suggest that the increased use of lethal suicide methods is reflected in the increase in suicide rates in Korean adolescents. The most fruitful approach to addressing the rises in jumping suicides among Korean adolescents and hanging suicides among adolescents in the United States may be through population-based initiatives to reduce the physical availability (e.g., limiting access to or fencing off tall structures) and the social acceptability (e.g., effective and responsible regulations for reporting suicide) of these methods. [ABSTRACT FROM AUTHOR]

Abstract: Manganese (Mn) is neurotoxic at high concentrations. However, Mn is an essential element that can protect against oxidative damage; thus, extremely low levels of Mn might be harmful. Our aim was to examine whether either high or low environmental Mn exposure is related to academic and attention function development among school-aged children. This cross-sectional study included 1089 children 8–11 years of age living in five representative areas in South Korea. Blood Mn, blood lead, and urine cotinine were measured. We assessed IQ with the Wechsler Abbreviated Scale of Intelligence; attention with a computerized continuous performance test called the Attention-deficit/hyperactivity disorder (ADHD) Diagnostic System (ADS), the Korean version of the Stroop Color-Word Test, the Children's Color Trails Test (CCTT), and the ADHD Rating Scale; academic functions with the Learning Disability Evaluation Scale (LDES); and emotional and behavioral problems with the Korean version of the Child Behavior Checklist (CBCL). We further assessed the presence of ADHD using a highly structured diagnostic interview, the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The median blood concentration of Mn was 14.14µg/L. We observed a nonlinear association between the CCTT2 completion time and the CPT commission error (F=3.14, p=0.03 and F=4.05, p=0.01, respectively). We divided the data into three groups: lower (<8.154µg/L), and upper 5th percentile (>21.453µg/L) and middle 90th percentile to determine whether a lack or overload of Mn could cause adverse effects. After adjusting for urine cotinine, blood lead, children's IQ, and other potential confounders, the high Mn group showed lower scores in thinking (B=−0.83, p=0.006), reading (B=−0.93, p=0.004), calculations (B=−0.72, p=0.005), and LQ (B=−4.06, p=0.006) in the LDES and a higher commission error in the CPT (B=8.02, p=0.048). The low Mn group showed lower color scores in the Stroop test (B=−3.24, p=0.040). We found that excess Mn in children is associated with lower scores of thinking, reading, calculation, and LQ in the LDES and higher scores of commission error in the ADS test. In contrast, lower Mn in children is associated with lower color scores in the Stroop test. The findings of this cross-sectional study suggest that excess exposure or deficiency of Mn can cause harmful effects in children. [Copyright &y& Elsevier]

Background Bisphenol A ( BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. Methods Urinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8-11 years. The main outcome measures were the Child Behavior Checklist ( CBCL) and the Learning Disability Evaluation Scale ( LDES). Results Urinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons. Conclusions Environmental exposure to BPA might be associated with childhood behavioral and learning development. The results suggest possible nonmonotonic relationships. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to comprehensively investigate the associations between a wide range of measures of dietary behaviors and learning disabilities and attention-deficit/hyperactivity disorder (ADHD) in community-dwelling Korean children in order to generate hypotheses for future work. The present study included 986 children [507 boys, 479 girls; mean (S.D.) age=9.1 (0.7) years] recruited from five South Korean cities. Children''s dietary behaviors were assessed by the mini-dietary assessment (MDA) for Koreans. It consists of ten items to assess the level of intake of dairy products, high-protein foods, vegetables, fried foods, fatty meats, salt, and sweetened desserts and whether the subject is eating three regular meals and has a balanced diet. Learning disability was assessed via the Learning Disability Evaluation Scale (LDES). ADHD was assessed via the Diagnostic Interview Schedule for Children version—IV and the ADHD rating scale, and ADHD-related behavioral problems were assessed via the Child Behavior Checklist. After adjusting for potential confounders, a high intake of sweetened desserts, fried food, and salt is associated with more learning, attention, and behavioral problems, whereas a balanced diet, regular meals, and a high intake of dairy products and vegetables is associated with less learning, attention, and behavioral problems. Our data suggest that existing encouraged dietary habits mostly have beneficial effects on learning, attention, and behavioral problems in Korean children. These findings are in general the same results in other studies on ADHD children in other countries. However, the cross-sectional study design prevents our ability to assess causal relationships. [Copyright &y& Elsevier]

Background: The present study assessed the association between blood lead and urinary cotinine levels and inattentive and hyperactive symptoms and neurocognitive performance in children. Methods: A total of 667 children (age range 8–11) were recruited from nine schools in five Korean cities. The teachers and parents completed the Korean version of the Attention-deficit/hyperactivity disorder Rating Scales (K-ARS), and the children performed neurocognitive tests. Blood lead and urinary cotinine levels were then measured. Results: The inattentive, hyperactive, and total scores of the teacher-rated K-ARS were positively associated with blood lead level, and the results of the continuous performance test (CPT), Stroop Color–Word Test, and Children’s Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, father’s educational level, maternal IQ, child’s IQ, residential area, birth weight, and cotinine (for lead) or lead (for cotinine). The association between blood lead level and commission errors score on the CPT disappeared when the effect of urinary cotinine level was controlled. Conclusions: These findings indicate that environmental exposure to tobacco smoke in children is associated with poor neurocognitive performance, and low levels of lead are associated with inattention and hyperactivity symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Neurotrophin-3 (NTF3), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, has been identified as a factor in the development of ADHD. We investigated the relationships between ADHD and NTF3 gene polymorphism. Methods: We conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 151 trios, and compared the intelligence quotient (IQ) and a continuous performance test (CPT) according to the genotype of two single-nucleotide polymorphisms (SNPs) (rs6332 and rs6489630) in the NTF3 gene. Results: In the case–control and family-based analyses, NTF3 was not significantly associated with ADHD. However, in the ADHD probands, the subjects with AA genotype in the rs6332 SNP had significantly higher mean T-scores for commission errors on the CPT than did those with the AG genotypes (p =0.045). The mean IQ of the ADHD probands who had the CC genotype of the rs6489630 SNP were higher compared with those who had the CT or TT genotype (p =0.035). The mean T-score for response time on the CPT was higher in the subjects with TT genotype in the rs6489630 SNP compared to those with the CC or CT genotype, even after adjusting for the effect of IQ (p =0.021). Conclusions: These results provide preliminary evidence of an association between NTF3 and the intelligence and selective attention deficit in the Korean population. [Copyright &y& Elsevier]

Abstract: Background: Exposure to environmental levels of lead (Pb) and manganese (Mn) has been associated with detrimental effects to neurodevelopment. However, little is known about the potential association between environmental levels of Pb and Mn on intelligence of children. The aims of the study were to investigate the association of community level of Pb and Mn with the intelligence of school-aged children, and to explore the implications of joint exposure to these two heavy metals. Methods: A cross-sectional examination of blood Pb and Mn concentrations was performed, and the intelligence quotient (IQ) was determined for 261 Korean children aged 8–11 years. Results: The mean blood concentrations of Pb and Mn were 1.73μg/dL (SD=0.8; median=1.55; range=0.42–4.91) and 14.3μg/L (SD=3.8; median=14.0; range=5.30–29.02), respectively. Both Pb and Mn showed significant linear relationship with full-scale IQ (Pb, β =−0.174, p =0.005; Mn, β =−0.123, p =0.042) and verbal IQ (Pb, β =−0.187, p =0.003; Mn, β =−0.127, p =0.036). Blood Pb (ΔR 2 =0.03) and Mn (ΔR 2 =0.01) explained 4% of the variances of the full-scale IQ and 5% of the variances of the verbal IQ. When Pb and Mn levels were entered as predictive variables, additive increase in the explained variances was observed. Finally, full-scale IQ and verbal IQ of the children with blood Mn>14μg/L showed significant association with Pb, whereas group with Mn<14μg/L did not, suggesting effect modification between Pb and Mn. Conclusions: The present study suggests the presence of additive interaction and effect modification between Pb and Mn on the intelligence of school-aged children, suggesting more attention should be paid to preventing the exposure of disadvantaged children to various combinations of toxic materials. [Copyright &y& Elsevier]

Abstract: Findings from preclinical and clinical research support the involvement of central noradrenergic dysregulation in the etiology of attention deficit hyperactivity disorder (ADHD). Previous studies have suggested that the alpha-2C-adrenergic receptor gene (ADRA2C) is associated with ADHD. The aims of this study were to examine the association between the ADRA2C (GT)n repeat polymorphism (STR marker adra2c1) and ADHD in a Korean sample. In this case-control and family-based association study, we assessed 184 ADHD probands, 150 normal controls, and 98 trios. There were no significant differences in the allele frequencies of the ADRA2C polymorphism between the ADHD and control groups (p >0.05). The overall allele-wise transmission disequilibrium test (TDT) analysis showed statistical significance (χ 2 =19.07, p =0.025). We found a trend for preferential transmission of the 183-bp allele (χ 2 =3.72, p =0.054), and a significantly lower-than-expected rate of transmission of the 187-bp allele (χ 2 =6.26, p =0.012). With regard to the temperament profiles of the Junior Temperament and Character Inventory (JTCI), the ADHD subjects with the 183/183 genotype at the ADRA2C polymorphism showed a trend toward a lower score in the Novelty Seeking (p =0.020) profile than did those with the other genotypes. Our findings provide important evidence that the ADRA2C polymorphism is involved in the etiology of ADHD in Korean subjects. In addition, our results provide evidence that the temperament of Novelty Seeking and ADHD might share molecular genetic characteristics related to the noradrenergic system. [Copyright &y& Elsevier]

Summary: Objective: Tonsillectomy is one of the most commonly performed procedures in children. However, parents often hesitate to agree to the procedure because of concerns of the possible harmful impact on their child''s psychological health. The present study was performed to examine the short-term psychological impact on children who had undergone tonsillectomy. Methods: Forty-three pediatric patients aged 3–11 years who underwent tonsillectomy were enrolled in the study. Postoperative pain was assessed using a 10-point visual analog scale (VAS) on postoperative days 1, 2, 7, and 21. The Korean version of the Child Behavior Checklist (K-CBCL) was given to the parents of the children to evaluate the psychosocial effect of tonsillectomy on the preoperative day and on postoperative day 21. Results: There were no significant differences in postoperative pain according to age, tonsil size, degree of adhesion, or operation time. There was no significant relationship between postoperative pain score and K-CBCL score. Sociality, total behavioral problems, externalizing problems, internalizing problems, anxiety/depression, social immaturity, and emotional lability domain scores on the K-CBCL were improved significantly. Conclusions: Improvements in general emotional and social status were observed at 3 weeks after tonsillectomy. Tonsillectomy itself does not have a harmful effect on children''s psychological status. [Copyright &y& Elsevier]

Virtual reality (VR), which offers an immersive experience, has been implemented into the education of pediatric patients to reduce peri-procedural anxiety. This randomized clinical trial evaluated the effect of VR, compared with standard video, on reducing anxiety and distress in pediatric patients undergoing chest radiography. A total of 120 children aged 4 to 8 years with scheduled chest radiography appointments were randomized into either the tablet or the VR group. Children in the tablet group experienced chest radiography indirectly with a 3 min tablet video, whereas those in the VR group received the same content via a VR experience. The distress of children was measured using the Observational Scale of Behavioral Distress (OSBD) scale. Parental presence and procedural outcomes were also recorded. The number of less distressed children (OSBD score < 5) was significantly higher in the VR group than in the tablet group (49 [81.7%]) vs. 32 [53.3%]) (p = 0.001). The OSBD scores, the need for parental presence, the procedure time, and the number of repeated procedures were all lower in the VR group. The immersive VR experience appears to decrease the degree of anxiety in children and increase the efficiency of the procedures compared with the tablet video with the same content. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a developmental disorder with a life-span disability. While diagnostic instruments have been developed and qualified based on the accuracy of the discrimination of children with ASD from typical development (TD) children, the stability of such procedures can be disrupted by limitations pertaining to time expenses and the subjectivity of clinicians. Consequently, automated diagnostic methods have been developed for acquiring objective measures of autism, and in various fields of research, vocal characteristics have not only been reported as distinctive characteristics by clinicians, but have also shown promising performance in several studies utilizing deep learning models based on the automated discrimination of children with ASD from children with TD. However, difficulties still exist in terms of the characteristics of the data, the complexity of the analysis, and the lack of arranged data caused by the low accessibility for diagnosis and the need to secure anonymity. In order to address these issues, we introduce a pre-trained feature extraction auto-encoder model and a joint optimization scheme, which can achieve robustness for widely distributed and unrefined data using a deep-learning-based method for the detection of autism that utilizes various models. By adopting this auto-encoder-based feature extraction and joint optimization in the extended version of the Geneva minimalistic acoustic parameter set (eGeMAPS) speech feature data set, we acquire improved performance in the detection of ASD in infants compared to the raw data set. [ABSTRACT FROM AUTHOR]

Aim: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes., Methods: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci., Results: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers., Conclusion: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population., (© 2024 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)