Hee-Jeong Yoo

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.

Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children.

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. Citation Hong SB, Im MH, Kim JW, Park EJ, Shin MS, Kim BN, Yoo HJ, Cho IH, Bhang SY, Hong YC, Cho SC. 2015. Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children. Environ Health Perspect 123:271–276; http://dx.doi.org/10.1289/ehp.1307420

Family-based association study between NOS-I and -IIA polymorphisms and autism spectrum disorders in Korean trios.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component and environmental risk factors. Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), may play a role in the development of ASD. We genotyped nine single nucleotide polymorphisms (SNPs) in the NOS‐I gene and nine SNPs in the NOS‐IIA gene and carried out the transmission disequilibrium test (TDT) and haplotype analysis in 151 Korean ASD trios. We found preferential transmission of the A allele of rs8068149 (P = 0.039) and G allele of rs1060826 (P = 0.035) of NOS‐IIA in ASD and the haplotype analysis revealed that the two haplotypes had significant associations (P = 0.014 and 0.031, respectively). The behavioral subdomain score of failure to use nonverbal behaviors to regulate social interaction in Autism Diagnostic Interview‐Revised (ADI‐R) was significantly higher in subjects with the GG or AG allele in rs1060826 of NOS‐IIA compared to those who had the AA allele (P = 0.027). These results provide significant but weak evidence for an association between NOS‐IIA and ASD in the Korean population.

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

BACKGROUND Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the alpha-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD. METHODS We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age- and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxe-wise t statistics using SPM2. RESULTS We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons). LIMITATIONS This study was limited by the small sample size, and we did not obtain genetic data from the controls. CONCLUSION Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

Different clinical courses of children exposed to a single incident of psychological trauma: a 30‐month prospective follow‐up study

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 childrens 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 childrens 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, childrens 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.

Association between dietary behaviors and attention-deficit/hyperactivity disorder and learning disabilities in school-aged children

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. Childrens 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.

Role of arachidonic acid-derived metabolites in the control of pulmonary arterial pressure and hypoxic pulmonary vasoconstriction in rats

BACKGROUND The roles of arachidonic acid (AA) metabolites in hypoxia-induced pulmonary vasoconstriction (HPV), a critical physiological mechanism that prevents ventilation/perfusion mismatch, are still incompletely understood. METHODS Pulmonary arterial pressure was measured in ventilated/perfused rat lungs. Isometric tones of rat intralobar pulmonary arteries were also measured, using a myograph. RESULTS Hypoxia (Po₂, 3%)-induced pulmonary arterial pressure increases (ΔPAP(hypox)) were stable with blood-mixed perfusate, but decayed spontaneously. ΔPAP(hypox) was inhibited by 29%, 16%, and 28% by the thromboxane A₂ (TXA₂) antagonist SQ-29548, the 5-lipoxygenase inhibitor, MK886, and the leukotriene D₄ antagonist, LY-171883, respectively. The prostacyclin synthase inhibitor tranylcypromine augmented ΔPAP(hypox) by 5%, whereas inhibition of cytochrome P450 did not affect ΔPAP(hypox). Consistently, the TXA₂ analogue U46619 increased ΔPAP(hypox) whereas prostacyclin abolished ΔPAP(hypox). However, leukotriene D₄ had no direct effect on ΔPAP(hypox). In the isolated pulmonary arteries, pretreatment with U46619 was essential to demonstrate hypoxia-induced contraction. CONCLUSIONS The above results suggest that TXA₂ and cysteinyl leukotrienes, other than leukotriene D₄, are endogenous factors that facilitate HPV in rats. The indispensable role of TXA₂-induced pretone in the HPV of isolated pulmonary arteries indicates that the signal from thromboxane receptors might be a critical component of oxygen sensation mechanisms.

Behavioral Characteristics of Prader-Willi Syndrome in Korea: Comparison With Children With Mental Retardation and Normal Controls

The purpose of this study was to examine the psychiatric characteristics of children with Prader-Willi syndrome in Korea, focusing particularly on their behavioral problems and obsessive-compulsive spectrum symptoms. Fourteen patients with Prader-Willi syndrome, together with their parents, underwent a psychiatric interview and parent questionnaire consisting of a Child Behavior Checklist. Twenty-four patients with mental retardation and 45 normal students were selected as control groups. Compared with the normal control group, the rates of inclusion in the clinical range and the mean scores with regard to social problems, thought problems, attention problems, delinquent behavior, aggressive behavior, externalizing problems, and total problems profiles were significantly higher (P < .01) in the Prader-Willi syndrome group according to the results of the Child Behavior Checklist. Compared with the mental retardation group, there was a statistically significant (P < .05) difference in the delinquent behavior profile. Comparing selected Child Behavior Checklist items related to obsessive-compulsive spectrum symptoms, the Prader-Willi syndrome group showed significantly more (P < .05) compulsion, skin picking, and stealing than the mental retardation or normal control groups. These findings suggest that children with Prader-Willi syndrome in Korea have many behavioral problems, including obsessive-compulsive spectrum symptoms, needing proper psychiatric attention and treatment. This is the first study in Korea to evaluate the psychiatric and behavioral characteristics of children with Prader-Willi syndrome. (J Child Neurol 2005;20:134—138).

Dopaminergic and Noradrenergic Gene Polymorphisms and Response to Methylphenidate in Korean Children with Attention-Deficit/Hyperactivity Disorder: Is There an Interaction?

OBJECTIVE We aimed to investigate the independent and interaction effects of dopamine transporter gene (DAT1), dopamine D4 receptor gene (DRD4), alpha-2A adrenergic receptor gene (ADRA2A), and norepinephrine transporter gene (NET1), with regard to treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). METHODS The participants of the study were 103 children and adolescents (ages 9.1±2.1 years) diagnosed as having ADHD according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria. They were enrolled in an 8-week, open-label trial of MPH. The good responder group was defined as subjects having an ≥50% decrease in the ADHD Rating Scale-IV (ADHD-RS) total score from the baseline, and at the same time a Clinical Global Impressions-Improvement Scale (CGI-I) score of 1 or 2, both at the 8th week of MPH treatment. Multivariate stepwise logistic regression was performed to examine the independent and interaction effects of genotypes on the dichotomized MPH treatment response. RESULTS Significant interaction effects on MPH response were detected between the genotypes of the DRD4 variable number of tandem repeat (VNTR) polymorphisms and those of either the ADRA2A DraI or the NET1 -3081(A/T) polymorphisms; significant interaction effects were also detected between the genotypes of the ADRA2A DraI polymorphisms and those of either the NET1 G1287A or the NET1 -3081(A/T) polymorphisms (Nagelkerke R(2)=0.40). No significant independent effect of a genotype was detected according to the stepwise logistic regression results. CONCLUSION The results suggest that genes involved in the dopaminergic and noradrenergic systems might interact to form important predictors of short-term response to MPH.