Soo-Churl Cho

Phthalates Exposure and Attention-Deficit/Hyperactivity Disorder in School-Age Children

BACKGROUND Very few studies have examined the association between attention-deficit/hyperactivity disorder (ADHD) and phthalate exposure in humans. The aim of this study was to investigate the impact of phthalates on symptoms of ADHD in school-age children. METHODS A cross-sectional examination of urine phthalate concentrations was performed, and scores on measures of ADHD symptoms and neuropsychological dysfunction with regard to attention and impulsivity were obtained from 261 Korean children, age 8-11 years. RESULTS Mono-2-ethylheyl phthalate (MEHP) and mono-2-ethyl-5-oxohexylphthalate (MEOP) for metabolites of Di-2-ethylhexylphthalate (DEHP) and mono-n-butyl phthalate (MNBP) for metabolites of dibutyl phthalate (DBP) were measured in urine samples. The mean concentrations of MEHP, MEOP, and MNBP were 34.0 microg/dL (SD = 36.3; range: 2.1-386.7), 23.4 microg/dL (SD = 23.0; range: .75-244.8), and 46.7 microg/L (SD = 21.4; range: 13.2-159.3), respectively. After adjustment for covariates, teacher-rated ADHD scores were significantly associated with DEHP metabolites but not with DBP metabolites. We also found significant relationships between the urine concentrations of metabolites for DBP and the number of omission and commission errors in continuous performance tests (CPT) after adjustment for covariates. CONCLUSION The present study showed a strong positive association between phthalate metabolites in urine and symptoms of ADHD among school-age children.

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Background Concern over phthalates has emerged because of their potential toxicity to humans. Objective We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning. Methods This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers. Results We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. Conclusion Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.

Regional cerebral perfusion abnormalities in attention deficit/hyperactivity disorder

Abstract.Objective: A voxel based investigation of cerebral blood flow was conducted to identify brain function differences in the resting state between children with Attention Deficit Hyperactivity Disorder (ADHD) and normal controls. Method: Using DSM-IV criteria, we selected 40 children with pure ADHD by various assessment scales, psychometric tools and a neuropsychological battery. All patients were examined by 99mTc-HMPAO brain SPECT. Seventeen normal controls were recruited from age, sex, and IQ-matched children whose previous SPECT, MRI, EEG and psychometric and neuropsychological findings had been normal. Using SPM methods, we compared SPECT images of ADHD patients and those of 17 control subjects on a voxel by voxel basis using t-statistics. Voxels with a p-value of less than 0.01 were considered to be significantly different. Result: Decreased cerebral blood flow in right lateral prefrontal cortex, right middle temporal cortex, both orbital prefrontal cortex and both cerebellar cortices were found in children with ADHD compared to the controls. In addition, the ADHD group showed increased blood flow in some parietal and occipital lobes (posterior brain regions) compared to the control group. Conclusion: Although the results should be interpreted cautiously, this study confirms the presence of functional defects in the prefrontal cortex and reports new problems in the limbic area, somatosensory areas and in the cerebellum during the resting state of brains of ADHD children.

The prevalence of and risk factors for erosive oesophagitis and non-erosive reflux disease: a nationwide multicentre prospective study in Korea

Background  Prospective nationwide multicentre studies that have evaluated endoscopic findings and reflux symptoms using a well‐designed questionnaire are very rare.

Co-exposure to environmental lead and manganese affects the intelligence of school-aged children

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 1.73 microg/dL (SD=0.8; median=1.55; range=0.42-4.91) and 14.3 microg/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, beta=-0.174, p=0.005; Mn, beta=-0.123, p=0.042) and verbal IQ (Pb, beta=-0.187, p=0.003; Mn, beta=-0.127, p=0.036). Blood Pb (DeltaR(2)=0.03) and Mn (DeltaR(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>14 microg/L showed significant association with Pb, whereas group with Mn<14 microg/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.

GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder that affects ∼5% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. Here we report a previously unidentified association between G protein–coupled receptor kinase–interacting protein-1 (GIT1) and ADHD in humans. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1−/− mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in ras-related C3 botulinum toxin substrate-1 (RAC1) signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes.

Effect of environmental exposure to lead and tobacco smoke on inattentive and hyperactive symptoms and neurocognitive performance in children.

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 Childrens Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, fathers educational level, maternal IQ, childs 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.

Association of 4-Repeat Allele of the Dopamine D4 Receptor Gene Exon III Polymorphism and Response to Methylphenidate Treatment in Korean ADHD Children

In the present study, we investigated the association between the 4-repeat allele at the dopamine receptor D4 (DRD4) gene and the response to treatment with methylphenidate (MPH) in Korean children with attention deficit hyperactivity disorder (ADHD). The study subjects were 83 children with ADHD (8.40±1.73 years) who were recruited from two child psychiatric clinics in South Korea. All of the drug-naive ADHD children were treated with MPH for about 8 weeks. An improvement of more than 50% in the ADHD Rating Scale-IV (ARS) scores after 8 weeks of treatment compared with the baseline ARS scores before the treatment was considered as a ‘good response’, whereas an improvement of less than (or equal to?) 50% was considered as a ‘poor response’. After the genotyping for DRD4 was performed, we investigated the association between the genotype at DRD4 and the response to MPH treatment. We performed a comparison of the response to MPH treatment between the two largest groups, viz. the subjects with and without the 4/4 genotype at DRD4. According to the ARS scores of the subjects as assessed by their parents and by their teachers, we found that while 71.1 and 80.0% (32/45 and 24/30), respectively, of those with a good response to MPH treatment showed the 4/4 genotype at DRD4, only 31.6 and 37.7% (12/38 and 20/53), respectively, of those with a poor response to MPH treatment showed the 4/4 genotype at DRD4 (Pearson χ2-values=12.926 and 13.737, respectively, both df=1, and both p<0.01). Our findings support the existence of an association between the 4-repeat allele at DRD4 and good response to MPH in Korean ADHD children.

Bisphenol A in relation to behavior and learning of school-age children

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.

A randomized controlled trial of the Korean version of the PEERS(®) parent-assisted social skills training program for teens with ASD.

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 (ps < 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.