Hanik K. Yoo

Putaminal gray matter volume decrease in panic disorder: An optimized voxel-based morphometry study

Our study aimed to identify gray matter volume differences between panic disorder patients and healthy volunteers using optimized voxel‐based morphometry. Gray matter volume was compared between 18 panic subjects and 18 healthy volunteers. Panic disorder severity scale (PDSS) and Zung self‐rating anxiety scale (Z‐SAS) were administered. Gray matter volumes of bilateral putamen were decreased in panic subjects relative to healthy comparison subjects (corrected P < 0.05). Decreased gray matter volume was also observed in the right precuneus, right inferior temporal gyrus, right inferior frontal gyrus, left superior temporal gyrus, and left superior frontal gyrus at a less conservative level of significance. PDSS score negatively correlated with gray matter volume in the left putamen, right putamen, right inferior frontal gyrus, and left superior frontal gyrus in panic subjects. The duration of illness negatively correlated with left putaminal gray matter volume. There was also a negative correlation between gray matter volume in right putamen and Z‐SAS score in panic subjects. The current study reports a putaminal gray matter volume decrease in panic subjects, which may be related to the clinical severity of panic disorder.

A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder.

OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourettes disorder. METHOD This 10-week multicenter, double-blind, randomized, placebo-controlled trial was conducted from August 2008 to April 2010. Children and adolescents (aged 6-18 years) with a DSM-IV diagnosis of Tourettes disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were randomly assigned (1:1 ratio) to placebo or aripiprazole. The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale (last observation carried forward). Assessments of safety and tolerability included spontaneously reported adverse events, extrapyramidal symptoms, serum prolactin level, metabolic variables, and other laboratory evaluations. RESULTS Of 61 subjects, 89% completed the study. Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean (SD) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo (-15.0 [8.4] and -9.6 [8.8], respectively, P=.0196). Response rate on the Tourettes Syndrome Clinical Global Impression-Improvement was 66% and 45% in the aripiprazole and placebo groups, respectively. Mean decrease in the Tourettes Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups (P=.0321). In general, aripiprazole was well tolerated and there were no early discontinuations due to adverse events. The incidence of treatment-emergent adverse events between the groups was not significantly different (P=.7550). While aripiprazole decreased serum prolactin concentration (P<.0001), it increased mean body weight, body mass index, and waist circumference significantly (P=.0055, P=.0142, and P=.0270, respectively). CONCLUSIONS In comparison with placebo, aripiprazole was efficacious, generally tolerated and safe in the short-term treatment of children and adolescents with Tourettes disorder. TRIAL REGISTRATION ClinicalTrials.gov identifier:NCT00706589.

Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridization.

Objectives Autism spectrum disorder (ASD) has been thought to have strong genetic background, but major contributing genes or associated molecular–genetic pathways are yet to be identified. To explore the idiopathic ASD-associated copy number variations (CNVs), we conducted case–control study using whole-genome copy number analysis. Methods Whole-genome microarray-based comparative genomic hybridization was carried out on 28 children (24 boys and four girls) diagnosed as ASD and 62 Korean adults (45 males and 17 females) without any signs of abnormalities and family history of genetic disorders as normal controls. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism were used for quantitative verification of the ASD-associated CNVs. Results Thirty-eight CNVs were identified. Among them, the distributions of copy number loss CNVs on 8p23.1 (odds ratio: 5.1, 95% confidence interval: 1.7–14.5, P=0.003) and on 17p11.2 (odds ratio: uncalculable because of zero cell, P=0.008) were found to be significantly different between ASD and control groups. DEFENSIN family occurs in a cluster at 8p23.1 region. Fluorescence in-situ hybridization and capillary electrophoresis-single-strand conformational polymorphism coherently showed reduced copy number of DEFENSIN in cases with 8p23.1 copy number loss CNV, which validated microarray-based comparative genomic hybridization results; but there are no known coding genes in the CNV on 17p11.2. Conclusion Our approach as well as results can help to elucidate the genetic mechanism of idiopathic ASD.

Effect of methylphenidate on the quality of life in children with epilepsy and attention deficit hyperactivity disorder

This open study explored whether methylphenidate could be tolerated and effective in improving the quality of life (QOL) and attention deficit hyperactivity disorder (ADHD) symptoms of children with epilepsy and ADHD. Twenty-five subjects (aged 10.1 +/- 3.0 years) with ADHD and epilepsy were recruited at an outpatient clinic in Seoul, Korea. We used the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), ADHD rating scale (ARS) and clinical global impression (CGI) in this study. Osmotic-controlled release oral delivery system (OROS) methylphenidate, 1.0 +/- 0.4 mg/kg/day, was administered for 55.2 +/- 7.5 days. The QOL subscales including physical restriction (p = 0.005), self-esteem (p = 0.002), memory (p < 0.001), language (p = 0.005), other cognition (p < 0.001), social interaction (p = 0.002), behaviour (p < 0.001), general health (p = 0.002) and QOL (p < 0.001) were significantly increased and the ARS (p < 0.001) and CGI-Severity of illness scores (p < 0.001) were significantly reduced after medication. Although 60% of subjects had experienced adverse effects, most were tolerable and only two subjects withdrew from the study owing to unbearable adverse effects (anorexia and insomnia). Two subjects had seizure attacks during the study period without having to discontinue the trial drug. Despite limitations related to the small sample size and the open design of the present pilot study, our results suggest that OROS methylphenidate may be well tolerated and effective in reducing ADHD symptoms and improving QOL in this patient population.

New functional single nucleotide polymorphism (Ala72Ser) in the COMT gene is associated with aggressive behavior in male schizophrenia

A new functional single nucleotide polymorphism (SNP) Ala72Ser in the COMT gene was discovered recently. The purpose of our study is to examine the association between Ala72Ser and Val158Met functional polymorphisms in COMT gene and homicidal behavior in schizophrenia. DNA was genotyped for the Ala72Ser and Val158Met SNPs of the COMT gene in a sample of 93 schizophrenic patients who committed homicide (H‐SCZ) and 100 schizophrenic patients who had never committed homicide (NH‐SCZ). A statistically significant difference was found in genotype distribution and allele frequencies in SNP Ala72Ser of COMT gene between H‐SCZ and NH‐SCZ group. In haplotype analysis, the frequency of the combination of high‐high activity allele (Ala‐Val) was lower in H‐SCZ group than in NH‐SCZ group (P = 0.000069). Our study showed a highly significant association between a COMT haplotype of two functional SNPs and aggressive behavior in schizophrenia.

Computerized assessment of cognitive impairment in narcoleptic patients

Objectives –  This study was aimed to investigate the comprehensive range of cognitive performance using the objective computerized assessment system in narcolepsy and age, gender, and IQ‐matched healthy comparison.

Microsatellite marker in gamma - aminobutyric acid - a receptor beta 3 subunit gene and autism spectrum disorders in Korean trios.

This study aimed to identify the association between gamma-aminobutyric acid-A (GABA-A) receptor subunit β3 (GABRB3) gene and autism spectrum disorders (ASD) in Korea. Fifty-eight children with ASD [47 boys (81.0%), 5.5 ± 4.1 years old], 46 family trios, and 86 healthy control subjects [71 males (82.6%), 33.6 ± 9.3 years old] were recruited. Transmission disequilibrium test revealed that, 183 bp long allele in GABRB3 gene was preferentially transmitted in families with ASD (p = 0.025), whereas a population-based case-control study, however, showed no association between ASD and GABRB3 microsatellite polymorphism. Our data provide preliminary evidence that GABRB3 gene is associated with ASD in Korea.

Neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy

We characterized the neuropsychological status of children with newly diagnosed idiopathic childhood epilepsy and measured differences in IQ between children with different types of epilepsy. The Korean Education Development Institute-Wechsler Intelligence Scale for Children (KEDI-WISC) was administered to 72 patients (35 males and 37 females), of mean age 8.7±2.6 years, with newly diagnosed idiopathic childhood epilepsy. Of these patients, 22 (30.6%) had generalized epilepsy, 48 (66.7%) localization-related epilepsy, and 2 (2.8%) mixed epilepsy. Children with generalized epilepsy and benign childhood epilepsy with centro-temporal spikes (BCECTS) were of similar verbal IQ and full-scale IQ, although performance IQ was significantly lower in patients with generalized epilepsy. Among children with BCECTS, those with unilateral spikes had higher full-scale and performance IQ scores than those with bilateral spikes. Follow-up studies on large numbers of patients are needed to determine the effects of epilepsy per se, and antiepileptic drugs, on intelligence.

Temperament and character factors in Korean children with seizure disorders.

Although the organic and psychosocial consequences of seizure disorders are thought to affect temperament and character patterns, these patterns in children with seizure disorders have not yet been investigated. We therefore investigated temperament and character patterns in Korean children with seizure disorders and their associations with seizure-related variables. The Korean version of the Junior Temperament and Character Inventory was used to assess temperament and character factors of 65 children with seizure disorders (32 boys, 33 girls; mean age, 10.6 ± 1.8 years) and 65 healthy controls matched for age and sex. Children with seizure disorders showed higher harm avoidance, and lower persistence, self-directedness, and cooperativeness than controls. In children with seizure disorders, character factors such as self-directedness, cooperativeness, and self-transcendence were significantly associated with seizure type, and cooperativeness was correlated with seizure severity. Novelty seeking and self-directedness were correlated with paternal educational level and parental economic status, respectively. These findings suggest that children with seizure disorders have distinctive temperament and character patterns, with seizure type being the most influential factor modulating character patterns.

Methylphenidate-osmotic-controlled release oral delivery system treatment reduces parenting stress in parents of children and adolescents with attention-deficit/hyperactivity disorder.

The aim of the current study was to investigate the effect of methylphenidate‐osmotic release oral delivery system (MPH‐OROS) treatment on parenting stress in parents of children and adolescents with attention‐deficit/hyperactivity disorder (ADHD).