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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 © 2012. Published by Elsevier Ireland Ltd.)

Background: Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD., Methods: Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2., Results: There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes., Conclusions: Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

Research on psychostimulants, analysis of animal models and genetic association studies all suggest that the brain-derived neurotrophic factor gene (BDNF) may be a good candidate for pharmacogenetic studies of attention deficit hyperactivity disorder (ADHD). Yet to date there have been no pharmacogenetic studies of BDNF in ADHD. A total of 102 drug-naive ADHD children (8.7±2.1 yr) were treated with osmotic release oral system-methylphenidate (OROS-MPH) for 12 wk, and four kinds of response criteria were applied, based first, on a combined threshold of the ADHD Rating Scale - IV (ARS) and the Clinical Global Impression - Improvement scale (CGI-I); second, on scores of 1 or 2 vs. 3-7 on the CGI - Severity scale; third, on a >50% reduction in ARS scores; and fourth, on satisfaction of all of the aforementioned criteria. The Val⁶⁶Met polymorphism of BDNF and six single nucleotide polymorphisms from the SLC6A2, ADRA2A and NTF-3 genes were tested for association with each criterion. Relative to other genotypes, homozygosity for the Val allele of the BDNF Val⁶⁶Met polymorphism was associated with a greater relative frequency of good response under all four response criteria (after controlling for baseline ARS score, age, gender, final dose (mg/kg) of OROS-MPH at 12 wk, and level of academic functioning). This association was significant at the uncorrected level for the first and third response criteria (p=0.013 and p=0.018, respectively) and significant at a Bonferroni-corrected level for the second and fourth response criteria (p=0.0002, p=0.0003, respectively). Our findings support an association between homozygosity for the Val allele of BDNF and better response to OROS-MPH in Korean ADHD children as assessed by four different response criteria.

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.

Objectives: The association between low blood lead levels (<5 μg/dL) and the inattention-hyperactivity symptoms and neurocognitive profiles of school-aged Korean children was investigated., Methods: We measured blood lead levels in 256 Korean children aged 8-10 years. Teachers completed the Attention-Deficit Hyperactivity Disorder Rating Scale (T-ARS)-IV to assess inattentive and hyperactive symptoms. Parents completed the Korean version of the Learning Disability Evaluation Scale (K-LDES). Children performed neurocognitive tests [The Continuous Performance Test (CPT), the Children's Color Trails Test, and the Stroop Color and Word Test (SCWT)]., Results: A linear regression analysis indicated that the blood lead concentrations were associated with the inattention scores [B=4.8, S.E.=1.6, 95% confidence interval (CI): 1.5-8.0], the hyperactivity subscores (3.1, 1.4, 0.3-5.9), and the total score (7.9, 2.9, 2.1-13.6) on the T-ARS; the number of omission errors on the CPT (20.6, 7.1, 6.5-34.6); the listening (-1.4, 0.7, -2.8 to -0.1), reading (-2.1, 0.7, -3.4 to -0.7), writing (-2.0, 0.7, -3.4 to -0.6), spelling (-2.2, 0.7, -3.7 to -0.7), and calculating (-1.8, 0.7, -3.1 to -0.4) scores on the K-LDES; and the color-word score on the SCWT (-6.7, 3.4, -13.3 to -0.1). A logistic regression analysis indicated that the probability of inattentive and hyperactive symptoms was increased with higher blood lead levels in boys with an odds ratio of 2.768 [B=1.018, S.E.=0.487, p=0.036, 95% CI: 1.066-7.187]., Conclusion: This study suggests that even low blood lead levels (<5 μg/dL) are associated with inattentive and hyperactivity symptoms and learning difficulties in school-aged children., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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.

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.

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 (c) 2010 Elsevier Inc. All rights reserved.)

Objective: The aims of this study were to investigate the prevalence, associated co-morbid psychiatric disorders and behavioral/emotional problems associated with the subtypes of specific phobia in children and adolescents., Methods: A total of 2673 randomly selected children and adolescents from Seoul, Korea were assessed using the parent version of the Diagnostic Interview Schedule for Children (DISC-IV) and Children's Behavior Checklist (CBCL). We analyzed differences in psychiatric co-morbidities and CBCL profiles among the subtypes of specific phobia., Results: The 1-year prevalence of specific phobia was 7.9% (95% CI 7.63-8.17). Animal phobia was associated with anxiety disorder (OR 8.68, 95% CI 1.91-39.51) and oppositional defiant disorder (OR 2.55, 95% CI 1.27-5.12). Nature-environment phobia was associated with anxiety disorder (OR 25.70, 95% CI 6.16-107.10). Blood-injection-injury phobia showed associations with attention-deficit/hyperactivity disorder (ADHD: OR 6.74, 95% CI 2.81-16.15). Subjects with nature-environment phobia scored higher than did controls on the anxious/depressed, social problems, attention problems, and total behavioral problem profiles of the CBCL. Subjects with blood-injection-injury phobia scored significantly higher than did controls on the attention problems, aggressive behaviors, and externalizing problem profiles., Conclusions: Contrary to animal phobias, nature-environment and blood-injection-injury phobias were associated with various behavioral and emotional problems and approximately correlated to their co-morbid psychiatric disorders. Among these subtypes, significant differences were found in demographic characteristics, co-morbid psychiatric disorders, and emotional/behavioral problems. These findings suggest that distinctive clinical characteristics might be related with different subtypes of specific phobia and clinician must consider psychiatric co-morbidities when treating children & adolescents with specific phobia., ((c) 2010 Elsevier Ltd. All rights reserved.)

Background: Most studies on temperamental and behavioral/emotional characteristics of oppositional defiant disorder (ODD) did not rule out the effect of comorbid attention-deficit/hyperactivity disorder (ADHD). The main objective of this study was to identify the temperamental and psychopathological patterns of ODD independent of comorbid ADHD. We also aimed to compare the patterns of temperament and psychopathology between ODD with and without ADHD., Method: Parents of 2673 students, randomly selected from 19 representative schools in Seoul, Korea, completed the Diagnostic Interview Schedule for Children Version IV. Among 118 children and adolescents with ODD diagnosed by the Diagnostic Interview Schedule for Children Version IV, the parents of 94 subjects (mean age, 10.4 +/- 3.0 years) and the parents of a random sample of 94 age- and gender-matched non-ODD/non-ADHD children and adolescents completed the parent's version of the Child Behavior Checklist (CBCL) and the Junior Temperament and Character Inventory., Results: Subjects with ODD showed temperament and character profiles of high Novelty Seeking, low Self-directedness, and low Cooperativeness, a distinct pattern on the CBCL, and were at increased risk for anxiety and mood disorders compared to the controls after controlling for the effect of comorbid ADHD. The children and adolescents with both ODD and ADHD showed decreased levels of Persistence and Self-directedness and higher scores on 4 subscales of the CBCL (Anxious/Depressed, Attention Problems, Delinquent Behaviors, and Aggressive Behaviors) compared to those with ODD only., Conclusions: Oppositional defiant disorder is associated with specific temperamental and behavioral/emotional characteristics, independent of ADHD. Moreover, the results of this study support that co-occurring ADHD and ODD have differentially higher levels of behavioral and emotional difficulties., (Copyright 2010 Elsevier Inc. All rights reserved.)

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 microg/L [geometric SD (GSD) = 2.2 microg/L; range, 0.5-445.4], 18.0 microg/L (GSD = 2.4; range, 0.07-291.1), and 48.9 microg/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.

Objective: The main objective of this study was to investigate the comorbid disorders and temperamental profiles of full syndrome and subthreshold attention-deficit/hyperactivity disorder (ADHD)., Method: A sample of 2,493 students was randomly selected from six representative elementary schools in Seoul, Korea. Among 245 children with full syndrome and subthreshold ADHD diagnosed by the diagnostic interview schedule for children-4th version, parents of 185 subjects (mean age 9.0 +/- 1.7 years) and of a random sample of 185 age- and gender-matched non-ADHD children have completed the parent's version of the children behavior checklist (CBCL) and the juvenile temperament and character inventory (JTCI)., Results: The prevalence rates of full syndrome and subthreshold ADHD were, respectively, 5.90% (95% confidence interval = 4.74-7.06) and 9.00% (95% confidence interval = 7.58-10.41). Subthreshold ADHD cases did not differ from full syndrome ADHD in any JTCI profile, showing high novelty seeking/low persistence/low self-directedness than controls. Subthreshold ADHD also showed increased risk for externalizing disorders and higher scores in eight CBCL scales (somatic complaints, anxious/depressed, social problems, attention problems, delinquent behaviors, aggressive behaviors, externalizing problems and total behavioral problems) compared to the controls., Conclusions: These results support the clinical relevance of subthreshold ADHD in Asian culture. Increased clinical awareness for children with subthreshold ADHD is needed.

Objectives: This study evaluated neurocognitive changes after switching from immediate release forms of methylphenidate (MPH-IR) to osmotic release oral system methylphenidate (OROS-MPH)., Methods: 102 children with attention-deficit/hyperactivity disorder (ADHD) participated in an open label, 28 day trial, performing neurocognitive test at baseline and at 28 days after the switch from MPH-IR to OROS-MPH., Results: There were significant improvements in the commission error and the reaction time of both visual and auditory continuous performance tests (CPTs) at 28 days after switching from MPH-IR to OROS-MPH. A positive correlation was observed between the improvement in parent/caregiver-rated IOWA Conners total score (Delta IOWA) and the reduction in commission error (r = 0.3, p = 0.001) and reduction in reaction time variability (r = 0.3, p = 0.006) of visual CPT. In a linear regression model, the change in parent/caregiver-rated IOWA Conners scale total scores were significant predictors of change in commission error (beta = 0.3, p = 0.005, CI = 0.4-2.3, adjusted R(2) = 0.12) and RT variability (beta = 0.3, p = 0.004, CI = 0.5-2.4, adjusted R(2) = 0.09) of visual CPT., Conclusions: These data suggest that MPH-IR may be successfully switched to OROS-MPH treatment with associated improvements in neurocognitive performance. Large-scale controlled trials are needed to replicate these findings., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

The purpose of this study was to evaluate the temperament and character of children and adolescents with anxiety disorders in samples from Korean community. The study subjects were children and adolescents diagnosed with social phobia (n = 66), separation anxiety disorder (n = 47), specific phobia (n = 415), and obsessive-compulsive disorder (n = 42) with the diagnostic interview schedule for children, version IV (DISC-IV) in representative community samples. Among these, we excluded other psychiatric disorder comorbid samples, with the exception of externalizing disorders. We assessed the subjects of each anxiety group using the junior temperament and character inventory (JTCI). Social phobias were significantly associated with high harm avoidance and low self-directedness on the JTCI. The association of specific phobias with high harm avoidance, and obsessive-compulsive disorder with low self-directedness was also significant. Separation anxiety disorder was not associated with any temperament and character on the JTCI. Children and adolescents with anxiety disorders have different temperaments and character profiles in accordance with diagnostic groups, which implies the specific pathophysiological mechanism of each anxiety disorder.

Objective: Treatment resistance in early onset schizophrenia (EOS) is one of the most challenging problems in child and adolescent psychiatry. We retrospectively examined the therapeutic dosage, clinical response, and side effect profiles of long-term clozapine treatment in Korean children and adolescents with refractory EOS or very early onset schizophrenia (VEOS)., Method: 26 refractory patients treated with clozapine for more than 1 year were analyzed. Efficacy was determined by comparing hospitalization rate and duration, before and after clozapine treatment. Tolerability was assessed through review of documented adverse events., Results: A significant reduction in hospital days per year was observed in 25 (96.2%) patients after clozapine treatment compared to before clozapine. Long-term benefit of the treatment was supported by a further reduction of the hospitalization rate in 14 patients treated with clozapine for more than 3 years. Neutropenia developed in 26.9% patients at 1 year and there was no agranulocytosis. Overall, eight male patients (8/12, 66.7%) and one female patient (1/14, 7%) developed neutropenia and out of the nine patients, seven patients were maintained and two patients were successfully rechallenged on clozapine., Conclusion: These findings suggest that long-term clozapine treatment may effectively reduce the amount of time Asian patients with refractory EOS or VEOS spend in the hospital. However careful monitoring of adverse events is required.

Previous studies have demonstrated that the MspI and DraI polymorphisms at the alpha-2A-adrenergic receptor gene (ADRA2A) are associated with ADHD. However, few studies have been designed to ascertain the association between the ADRA2A genotypes and the performance on neurocognitive measures in ADHD. The aims of this study were to examine the association of the ADRA2A MspI and DraI polymorphisms with ADHD in Korean subjects, and to determine the relationship between the genotypes of these two polymorphisms and the candidate endophenotypes, as measured by the continuous performance test (CPT). In a case-control study, we assessed 186 ADHD probands and 150 normal controls. One hundred eight trios were studied in a family based association analysis. The transmission disequilibrium test (TDT) analysis showed preferential transmission of the C allele of the DraI polymorphism (chi(2) = 5.88, P = 0.015). In the haplotype analyses, a trend of over-transmission of haplotype C/C was observed (chi(2) = 3.80, P = 0.051). The homozygous subjects for the C allele (C/C genotype) at the DraI polymorphism showed a trend toward a higher mean T-score with respect to the response time variability profiles of the CPT than did those with the other genotypes (C/T + T/T genotypes; P = 0.042). The homozygous subjects for the G allele (G/G genotype) at the MspI polymorphism showed a tendency to have a lower mean T-score with respect to the response time variability profiles of the CPT (P = 0.068). The results of this study provide important evidence for the involvement of the ADRA2A MspI and DraI polymorphisms in the etiology of ADHD in Korean subjects. In addition, our results provide evidence for the possible role of these two polymorphisms in ADHD symptom expression, such as increased response time variability., (2008 Wiley-Liss, Inc.)

Introduction: Dopamine receptor polymorphisms have been associated with specific patterns of novelty seeking (NS) temperamental nature and frontal executive function. In addition, carriers of dopamine receptor type 2 (DRD2)-TaqI A1 have been hypothesized to be potentially vulnerable to addictive behaviors. In the present study, the association between dopamine D2 polymorphisms, NS, and frontal executive function was studied., Methods: Thirty-seven methamphetamine (MA)-dependent subjects and 40 healthy comparison subjects participated in the current study. The severity of addiction, NS temperament, and frontal executive functions were measured using the Addiction Severity Index, the NS subscale in the Temperament and Character Inventory, and the Wisconsin Card Sorting Test, respectively. All subjects were genotyped with regard to DRD2-TaqI polymorphisms., Results: The prevalence of DRD2-TaqI A1 allele polymorphisms was greater in the MA-abuser group than in the comparison group. Patients with MA dependence also had higher NS characteristics and high scores in total trials, errors, and perseverative errors of the Wisconsin Card Sorting Test than comparison subjects. Within patients with MA dependence, the subgroup of DRD2-TaqI A1 carrier had greater NS scores relative to those without, whereas there was only a trend level of lower frontal executive function in the first subgroup., Conclusion: In the present study, the MA-dependent patients with DRD2-TaqI A1 allele had significantly greater NS scores and lower frontal executive function with a trend level than those without. These preliminary results suggest that MA-dependent patients may have the possibility of genetic and biogenic vulnerability to MA.

Aims: The purpose of the present study was to assess patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder (ADHD) and to investigate the relationship between patterns of temperament and character and the severity of ADHD symptoms., Methods: Fifty-one children who met DSM-IV criteria for ADHD and 51 age- and sex-matched healthy comparison subjects completed the Junior Temperament and Character Inventory (JTCI) and the DuPaul's ADHD Rating Scale (ARS-IV)., Results: Children with ADHD had significantly higher scores of Novelty Seeking and lower scores of Self-directedness in both parents' rating and children's self-rating. In addition, low Self-directedness scores predicted higher total scores of ARS-IV., Conclusions: In a clinical sample of Korean children with ADHD, a distinct pattern of temperament and character was found. The current findings suggest that low Self-directedness may be related to the severity of ADHD symptoms.

The objective of this study was to examine the associations between symptoms of attention-deficit/hyperactivity disorder (ADHD), depression, and suicide in Korean female adolescents. It was hypothesized that the relationship between ADHD symptoms and suicidal ideation would be mediated by the level of depressive symptoms. Seven hundred and eighty-eight high school girls completed the Conners/Wells Adolescent Self-Report Scale: Short Form, Children's Depression Inventory, and Reynolds Suicidal Ideation Questionnaire. Path analyses were conducted using the statistical program, AMOS version 4.0, to determine the best fitting model. The conduct, cognitive, and hyperactivity problems of the ADHD symptoms in each domain were associated positively with the depressive symptoms, with the depressive symptoms being associated with suicidal ideation. This initially proposed model represented an acceptable fit to the data (root mean square error of approximation, RMSEA=0.077; normed fit index, NFI=0.998; non-NFI, NNFI=0.990; comparative fit index, CFI=0.998). The inclusion of a direct path from the conduct problems of ADHD symptoms to suicidal ideation significantly improved the model fit (RMSEA=0, NFI=1, NNFI=1, CFI=1). The results of our study suggest that depressive symptoms partially mediate the relationship between ADHD symptoms and suicidal ideation, and that the conduct problems of ADHD symptoms are associated with suicidal ideation both directly and indirectly via the depressive symptoms in Korean female adolescents., (2007 Wiley-Liss, Inc.)

In a sample of children with attention-deficit hyperactivity disorder (ADHD), a voxel based investigation of regional cerebral blood flow (rCBF) during resting state was conducted to identify functional differences between non-responders to methylphenidate (MPH) and responders. Thirty-four children with ADHD were examined by technetium-99m-hexamethylporphylenamine oxime (HMPAO) SPECT. According to clinical response after 8 weeks of treatment with MPH, they were classified as non-responders to MPH and responders. Using SPM analysis, we compared the SPECT images of non-responders to MPH with those of responders. Non-responders to MPH had higher rCBF in the left anterior cingulate cortex, the left claustrum, the right anterior cingulate cortex, and the right putamen relative to responders. In addition, lower rCBF was found in the right superior parietal lobule in non-responders to MPH relative to responders. Further stepwise discriminant analysis revealed that 88.2% could be correctly classified as either non-responders to MPH or responders when considering the extracted rCBF values in the left anterior cingulate cortex, the left claustrum, and the right superior parietal lobule. The current findings suggest that non-responders to MPH may have different patterns of rCBF in brain regions, which have been known as a part of frontal-striatal circuitry and posterior attentional system, respectively.

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 or equal to [corrected] 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 [corrected] 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 chi2-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.

Objective: Altered concentrations of the brain metabolites, including N-acetyl-aspartate (NAA) and myo-inositol (MI), may indicate neurotoxicity associated with drug abuse. In this study, the authors explored differences in brain metabolites between abstinent methamphetamine (MA) abusers and healthy comparison subjects and the associations between metabolite concentrations and clinical characteristics., Method: Proton magnetic resonance spectroscopy (MRS) was performed on 30 abstinent MA abusers and 20 healthy comparison subjects. Two sets of MA user subgroups were defined depending on abstinence duration (greater or less than 6 months) or the total cumulative MA dose (greater or less than 100 g lifetime). NAA and other metabolites were measured in the frontal gray and white matter and compared between MA abuser groups and healthy comparison subjects., Results: MI concentrations were higher for the MA abusers relative to healthy comparison subjects. NAA concentration was lower in frontal white matter of MA abusers with a 'large' cumulative dose relative to those with a 'small' cumulative dose and to healthy comparison subjects. Additionally, in MA abusers NAA concentrations in frontal white matter correlated inversely with the cumulative MA dose. In contrast, there was no significant difference in frontal gray matter NAA concentration among the three groups. However, frontal gray matter NAA concentrations for MA abusers correlated negatively with the total cumulative MA dose and positively with the duration of abstinence. There were no differences between the different MA user groups for MI., Conclusions: The current findings suggest that MA-induced metabolic alterations of frontal gray and white matter are dose-dependent, for primarily male subjects. Additionally, these findings potentially suggest that the MA-related abnormalities may, in part, recover with abstinence in gray matter, but not in the white matter regions.

The dopamine transporter gene (DAT1) has been extensively studied as one of the candidate genes in attention-deficit/hyperactivity disorder (ADHD). Several studies have reported on the association between the DAT1 10-repeat allele and cognitive variables in ADHD. However, few studies have been designed to ascertain the association between DAT1 genotypes other than the 10-repeat allele and cognitive endophenotypes in ADHD. The aim of this study was to examine the relationship between the DAT1 genotypes and the candidate endophenotypes, inattention and impulsivity symptoms, as measured by the continuous performance test (CPT), in a Korean sample of 85 children diagnosed with DSM-IV ADHD. Compared to the normal control group, the frequencies of the 9/10 genotype were significantly higher in the ADHD probands (chi(2)=13.45, p=0.02, OR=4.12, 95% CI: 2.21-12.34) and parents of probands (chi(2)=11.60, p=0.03). The 9-repeat allele frequencies were significantly higher in the ADHD probands (chi(2)=11.55, p=0.03, OR=4.43, 95% CI: 1.55-11.78) and parents of probands (chi(2)=12.70,p=0.03) than the normal control group. Compared to the ADHD probands without the 9-repeat allele (n=74), the mean T-score, with regard to the commission errors of the CPT, was significantly higher (p<0.05) in the ADHD probands with the 9-repeat allele (n=11). Compared to the ADHD probands with other DAT1 genotypes, the mean T-score, with respect to the commission errors of the CPT, was significantly higher in the ADHD probands with the 9/10 genotype (p<0.05). The results of this study suggest the possibility of an association between the DAT1 9-repeat allele and the impulsivity phenotype of ADHD.

Aims: To examine the clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder (ADHD)., Methods: The present study included 85 male alcoholics who were diagnosed as having DSM-IV alcohol dependence. A total of 28 (32.9%) alcoholics were diagnosed as having DSM-IV ADHD with ongoing symptoms in adulthood. For the evaluation of their psychiatric conditions, the alcohol dependence scale (ADS), Beck depression inventory (BDI), Beck anxiety inventory (BAI), Barratt impulsiveness scale (BIS), brief anger-aggression questionnaire (BAQ), overt aggression scale (OAS), codependence test, and obsessive compulsive drinking scale (OCDS) were administered. The genotype frequencies of the dopamine type 2 receptor gene (DRD2), aldehyde dehydrogenase type 2 gene (ALDH2), functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR), and catechol-O-methyltransferase gene (COMT) polymorphisms were examined., Results: Compared with alcoholics without ADHD, the mean ages for the onset of pathological drinking and alcohol withdrawal hallucinations were significantly earlier in alcoholics with ADHD. There was also a significant difference in the history of antisocial behaviour between the two groups. Compared with alcoholics without ADHD, the mean scores of the ADS, BDI, BAI, OAS, and OCDS were significantly higher in alcoholics with ADHD. With regard to the codependence test results, the mean scores of the interpersonal problem, low self-esteem and anxiety/fear subscales, and the mean total score of the codependence test were significantly higher in alcoholics with ADHD when compared with those without ADHD. There were no significant differences in the genotype frequencies of the DRD2, ALDH2, 5-HTTLPR, and COMT polymorphisms between alcoholics with and without ADHD., Conclusions: The results of this study suggest that the comorbidity of alcohol dependence and ADHD in this Korean sample forms a distinct clinical phenotype that shows an increased severity of alcohol-related symptoms and behavioural/emotional problems and that ADHD is associated with an increased risk for the early onset of alcohol dependence in Korean male alcoholics.

Objective: A voxel based investigation of cerebral blood flow was conducted to identify brain functional differences during resting state between children with developmental language disorder (DLD) and normal controls., Method: Using DSM-IV criteria, we selected 21 children with DLD. All children were examined by technetium-99m-HMPAO Brain SPECT. Using SPM analyses, we compared the SPECT images of children with DLD and those of 17 control subjects on a voxel by voxel basis using ANCOVA covarying for age., Results: Reduced cerebral blood flow in the right putamen,the right inferior parietal cortex, and the left globus pallidus were found in children with DLD versus the controls. However, no area of increased cerebral blood flow was observed in children with DLD compared to the controls., Conclusion: Though results should be interpreted cautiously, this study confirms the presence of functional defects in the basal ganglia and the inferior parietal lobe during the resting state of the brains of children with DLD. It also gives further evidence for functional deficits in basal ganglia as an important factor in the etiology of DLD.

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.

Neuroleptic Malignant Syndrome (NMS) is a rare, potentially fatal and idiosyncratic drug reaction. It is characterized by a sudden loss of body temperature control, renal and respiratory failure, muscle rigidity, loss of consciousness and impairment of autonomic nervous system. Although NMS was previously associated with the use of classical high-potency neuroleptics, cases have started to emerge with atypical neuroleptics. This article discusses the first case of NMS in a child, induced by the use of risperidone, olanzapine and quetiapine.

The objective of this study was to evaluate the relationship between attention deficit-hyperactivity/impulsivity symptoms and Internet addiction. In total, 535 elementary school students (264 boys, 271 girls; mean age, 11.0 +/- 1.0 years) were recruited. The presence or severity of Internet addiction was assessed by the Young's Internet Addiction test. Parents and teachers of the children completed the DuPaul's attention deficit hyperactivity disorder (ADHD) rating scale (ARS; Korean version, K-ARS) and Child Behavior Checklists. Children with the highest and lowest quartiles in K-ARS scores were defined to be in ADHD and non-ADHD groups, respectively. Five children (0.9%) met criteria for a definite Internet addiction and 75 children (14.0%) met criteria for a probable Internet addiction. K-ARS scores had significant positive correlations with Young's Internet Addiction test scores. The Internet addiction group had higher total scores of K-ARS and ADHD-related subcategories in the Child Behavior Checklists than the non-addiction group. The ADHD group had higher Internet addiction scores compared with the non-ADHD group. Therefore, significant associations have been found between the level of ADHD symptoms and the severity of Internet addiction in children. In addition, current findings suggest that the presence of ADHD symptoms, both in inattention and hyperactivity-impulsivity domains, may be one of the important risk factors for Internet addiction.