Boong Nyun Kim

Regional cerebral blood flow in children with attention deficit hyperactivity disorder: Comparison before and after methylphenidate treatment

Differences in brain activity of children with attention deficit hyperactivity disorder (ADHD) have been compared to normal healthy controls, suggesting neural correlates of cognitive/behavioral symptoms. Symptoms are improved with methylphenidate treatment but limited sources can be cited to show how brain activity in ADHD is altered after pharmacologic treatment. We investigated how long‐term oral medication of methylphenidate affects the resting regional cerebral blood flow (rCBF) in ADHD children, using single photon emission computerized tomography (SPECT). rCBF was decreased in the orbitofrontal cortex and middle temporal gyrus in the right hemisphere whereas it was increased in the dorsomedial prefrontal and somatosensory area bilaterally in drug‐naïve ADHD children compared to control child subjects. After treatment with methylphenidate, the extent of hyperperfusion in the somatosensory area was reduced and significant reduction of rCBF was found in the right striatum for the first time. Methylphenidate treatment also resulted in rCBF increase in superior prefrontal and reduction in ventral higher visual areas bilaterally. The results indicated that improving ADHD symptom after methylphenidate is associated with normalization of abnormally reduced orbitofrontal activity and abnormally increased somatosensory cortical activity. These changes were accompanied with reduced striatum activity lower than that of normal controls. These changes might be associated with improving ADHD to control attention and motor response to irrelevant environmental stimuli after methylphenidate treatment. Hum. Brain Mapp 24:157–164, 2005.

Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD

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.

The relationship between temperament and character and psychopathology in community children with overweight.

ABSTRACT. This study investigated the relationship between temperament and character and psychopathology in at risk of overweight and overweight children. The Child Behavior Checklist (CBCL) and the Junior Temperament and Character Inventory (JTCI) questionnaires were administered to 453 children (10-12 years of age, 203 boys and 250 girls) in Kimpo, South Korea. Subjects were divided into three groups; (1)nonoverweight children (n = 345), (2) children at risk of overweight (n = 72), and (3) overweight children (n = 36). CBCL and the JTCI scores were compared among three groups. In addition, the relationships between subscales of the CBCL and the JTCI were evaluated. On the CBCL, overweight children had higher scores in social problems, delinquent problems, and total problems compared to nonoverweight children. Children at risk of overweight showed higher scores only in social problems compared to nonoverweight children. On the JTCI, lower persistence and tendency of higher novelty seeking was observed in overweight children compared to nonoverweight children. Persistence scores were negatively correlated with scores of delinquent problems, externalizing problems, and total problems in overweight children. Compared to nonoverweight and children at risk of overweight, overweight children had distinct patterns of temperament and character that were related to the specific psychopathology.

Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios

The dopamine (DA) system has been implicated in attention deficit hyperactivity disorder (ADHD) based on pharmacologic evidence. Because of an interaction between the serotonin (5‐HT) and DA systems, the serotonin transporter gene (SLC6A4) has been considered as a candidate ADHD susceptibility gene. Two common polymorphisms, 5‐HTTLPR and the intron 2 VNTR, have been studied for association in ADHD, with both positive (increased frequency of long allele of 5‐HTTLPR and decreased frequency of 12 repeats of the intron 2 VNTR) and negative findings. However, there has not been an association study in an East Asian ADHD population. In this study, we examined the genotypes of these two polymorphisms in 126 Korean ADHD families and investigated linkage disequilibrium (LD) between SLC6A4 and ADHD, using the transmission disequilibrium test (TDT) and haplotype analysis. Additionally, association with quantitative measures of inattention, hyperactivity‐impulsivity, and overall severity was tested using logistic regression and QTDT analysis. TDT of both polymorphisms and haplotype analysis failed to detect LD. However, after excluding ADHD NOS subtype, TDT revealed nominally significant LD between 5‐HTTLPR and ADHD (χ2 = 4.9, P = 0.036). QTDT revealed positive association between 12 repeats of the intron 2 VNTR and attention (P = 0.031), but case‐control and TDT logistic regression analyses were negative. These markers have low heterozygosity in the Korean population, which would be expected to reduce the power of association. This result suggests that future studies should include more polymorphic markers and subjects to thoroughly investigate a potential association between SLC6A4 and ADHD in the Korean population.

Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder.

BACKGROUND Previous studies have implicated the relationship between environmental phthalate exposure and attention deficit hyperactivity disorder (ADHD) symptoms of childhood, but no studies have been conducted in children who have a confirmed diagnosis of ADHD obtained through meticulous diagnostic testing. We aimed to determine whether phthalate metabolites in urine would be higher in children with ADHD than in those without ADHD and would correlate with symptom severity and cortical thickness in ADHD children. METHOD A cross-sectional examination of urine phthalate metabolite concentrations was performed; scores for ADHD symptoms, externalizing problems, and continuous performance tests were obtained from 180 children with ADHD, and brain-imaging data were obtained from 115 participants. For the control group, children without ADHD (N = 438) were recruited. Correlations between phthalate metabolite concentrations and clinical measures and brain cortical thickness were investigated. RESULTS Concentrations of phthalate metabolites, particularly the di(2-ethylhexyl) phthalate (DEHP) metabolite, were significantly higher in boys with ADHD than in boys without ADHD. Concentrations of the di-n-butyl phthalate (DBP) metabolite were significantly higher in the combined or hyperactive-impulsive subtypes compared to the inattentive subtype, and the metabolite was positively correlated with the severity of externalizing symptoms. Concentrations of the DEHP metabolite were negatively correlated with cortical thickness in the right middle and superior temporal gyri. CONCLUSIONS The results of this study suggest an association between phthalate concentrations and both the diagnosis and symptom severity of ADHD. Imaging findings suggest a negative impact of phthalates on regional cortical maturation in children with ADHD.

Are Teacher Ratings and Parent Ratings Differently Associated with Children's Intelligence and Cognitive Performance?

Objective The present study investigated whether teacher ratings and parent ratings of inattentive or hyperactive/impulsive symptoms were differently associated with intelligence or cognitive performance in Korean children. Methods Six hundred sixty-seven children were recruited from nine schools in five Korean cities. The teachers and parents of 580 of these children (9.0±0.7 years old, 333 boys and 306 girls) completed the Korean version of the Attention-Deficit/Hyperactivity Disorder Rating Scales (K-ARS), and the children performed the abbreviated form of the Korean Educational Development Institute-Wechsler Intelligence Scales (KEDI-WISC) and a neurocognitive battery consisting of the continuous performance test, the Childrens Color Trails Test, and the Stroop Color-Word Test. Diagnosis of full-syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD) were based on the Diagnostic Interview Schedule for Children Version-IV (DISC-IV). Results The level of agreement between teacher and parent ratings was low (r=0.21-0.26) in children with full-syndrome and subthreshold ADHD and low to moderate (r=0.31-0.41) in the normative sample. Teacher-rated ARS showed significant correlations with most sub-scores of KEDI-WISC and the neurocognitive battery both in the normative sample (r=-0.50-0.37) and in children with full-syndrome and subthreshold ADHD (r=-0.26-0.29). Correlations between parent-rated ARS and cognitive tests were lower and were found in fewer subscales of tests. Conclusion These results suggest the importance of considering the teachers report of a childs school functioning during the assessment of ADHD.

A 12-Month Prospective, Observational Study of Treatment Regimen and Quality of Life Associated With ADHD in Central and Eastern Europe and Eastern Asia

Objectives: This prospective, observational, non-randomized study aimed to describe the relationship between treatment regimen prescribed and the quality of life (QoL) of ADHD patients in countries of Central and Eastern Europe (CEE) and Eastern Asia over 12 months. Methods: 977 Male and female patients aged 6-17 years seeking treatment for symptoms of ADHD were assessed using the Child and Adolescent Symptom Inventory-4 Parent Checklists, and the Clinical Global Impressions-ADHD-Severity scale. QoL was assessed using the Child Health and Illness Profile-Child Edition parent report form. Patients were grouped according to whether they were prescribed psycho- and/or pharmacotherapy (treatment) or not (no/‘other’ treatment). Results: No statistically significant differences were observed between cohorts (treatment vs. no/‘other’ treatment) in terms of change in QoL, although there was improvement over 12 months, with a greater improvement experienced by patients in the treatment cohort in both study regions (CEE and Eastern Asia). Psychoeducation/counselling and methylphenidate were the predominant ADHD treatments prescribed. Conclusions: Although both treatment and no/‘other’ treatment cohorts showed improvements in mean QoL over 12 months, the difference was small and not statistically significant. A major limitation was the higher than anticipated number of patients switching treatments, predominantly from the no/‘other’ treatment cohort.

Maternal Stress and Depressive Symptoms and Infant Development at Six Months: the Mothers and Children's Environmental Health (MOCEH) Prospective Study

Our objective is to evaluate the relationships between prenatal maternal stress and depressive symptoms, respectively, and infant neurodevelopment at 6 months, adjusted for heavy metals and oxidative stress. This research is a part of a multi-center birth cohort study in South Korea. Information on stress and depressive symptoms was collected during the first trimester using Psychosocial Well-Being Index Short Form (PWI-SF) and Center for Epidemiological Studies Depression Scale (CES-D). The Korean Bayley Scales of Infant Development-II assessment (BSID-II), which includes the standardized mental development index (MDI) and psychomotor developmental index (PDI), and Korean Ages & Stages Questionnaires (K-ASQ) were applied to infants at six months of age. A higher index score indicates better development. Among 641 babies, 320 were female (50%). Maternal PWI ≥ 29 (vs. PWI ≤ 18) during early pregnancy was associated with a decrease in MDI scores of 5.37 points (P = 0.02) after adjusting for socioeconomic factors. Maternal CES-D ≥ 26 (vs. CES-D ≤ 10) during early pregnancy was associated with a decrease in MDI scores of 8.18 points (P = 0.01). The associations remained significant even after adjustment for lead, cadmium, and MDA levels (P < 0.05). However, no association was found between maternal PWI/CES-D and PDI score. No interaction was observed between stress and lead exposure. We found an inverse association between prenatal maternal stress and depressive symptoms, and MDI scores in 6-month-old infants after adjustment for prenatal lead exposure, which is known to affect cognitive function negatively.

P01-188 - Regional brain perfusion differences associated with norepinephrine transporter gene polymorphisms in ADHD

Objectives The aim of this study was to examine whether the presence of risk alleles of the norepinephrine transporter gene (SLC6A2) polymorphisms is associated with differences in regional cerebral blood flow (rCBF) measured by 99m Tc-HMPAO single photon emission computerized tomography in a Korean sample of ADHD. Methods The present study included 24 children with ADHD (9.5±2.4 years), consisting of 20 boys and 4 girls, aged 6-16 years. We investigated the G1287A and -3081(A/T) polymorphisms of the SLC6A2. The rCBF was compared between the ADHD subjects with and without risk alleles at the G1287A polymorphism and at the -3081(A/T) polymorphism. Image analyses were performed with voxelwise t -statistics using SPM2. Results 1) The ADHD subjects with the A allele (risk allele) at the G1287A polymorphism showed reduced perfusion in the left middle frontal gyrus, left inferior parietal lobule, precuneus, right superior frontal gyrus, and right superior parietal lobule as compared with ADHD subjects without the A allele (p 2) The ADHD subjects with the A allele at the G1287A polymorphism showed increased perfusion in the right middle frontal gyrus, right middle temporal gyrus, right superior temporal gyrus, right fusiform gyrus, right precentral gyrus, and right anterior lobe of cerebellum as compared with ADHD subjects without the A allele (p 3) No significant perfusion differences were found between ADHD subjects with and without the T allele (risk allele) at the -3081(A/T) polymorphism. Conclusion Our findings suggest that the SLC6A2 G1287A polymorphism might exert differential effects on rCBF in children with ADHD.