Un-Sun Chung

Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity disorder in a Korean sample

BackgroundThe purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population.MethodsWe conducted a case–control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 149 trios, and compared scores from the continuous performance test (CPT), the Children’s Depression Inventory (CDI), and the State-Trait Anxiety Inventory for Children (STAIC) according to the genotype of the glutamate receptor genes.ResultsThere were no significant differences in the genotype or allele frequencies of the GRIN2A rs8049651, GRIN2B rs2284411, or GRM7 rs37952452 polymorphisms between the ADHD and control groups. For 148 ADHD trios, the TDT analysis also showed no preferential transmission of the GRIN2A rs8049651 or GRIN2B rs2284411 polymorphisms. However, the TDT analysis of the GRM7 rs3792452 polymorphism showed biased transmission of the G allele (χ2 = 4.67, p = 0.031). In the ADHD probands, the subjects with GG genotype in the GRM7 rs37952452 polymorphism had higher mean T-scores for omission errors on the CPT than did those with the GA or AA genotype (t = 3.38, p = 0.001). In addition, the ADHD subjects who were homozygous for the G allele in the GRM7 rs37952452 polymorphism had higher STAIC-T (t = 5.52, p < 0.001) and STAIC-S (t = 2.74, p = 0.007) scores than did those with the GA or AA genotype.ConclusionsThese results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population.

No Evidence of an Association between Norepinephrine Transporter Gene Polymorphisms and Attention Deficit Hyperactivity Disorder

Neurobiological and pharmacological research has suggested that dysregulation of the central noradrenergic systems might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Previous studies have demonstrated that the norepinephrine transporter gene (SLC6A2) is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 G1287A and –3081(A/T) polymorphisms with ADHD in Korean children and adolescents, and to determine the relationships of the genotypes of these two polymorphisms with continuous performance test results and the Junior Temperament and Character Inventory profiles of ADHD. In a case-control study, we assessed 186 ADHD probands and 150 normal controls; 109 trios were studied in a family-based association analysis. There were no significant differences in the genotype or allele frequencies of the SLC6A2 G1287A and –3081(A/T) polymorphisms between the ADHD and control groups (p > 0.05). In the transmission disequilibrium test analyses, there was no evidence for biased transmission of any of the alleles of the SLC6A2 G1287A and –3081(A/T) polymorphisms. In the haplotype analyses of these two polymorphisms, the global and individual χ2 tests showed no significant associations between any of the haplotypes and ADHD. There were no significant differences with respect to the continuous performance test results and the Junior Temperament and Character Inventory profiles in the ADHD probands according to the genotypes of the SLC6A2 G1287A and –3081(A/T) polymorphisms. Our findings do not support SLC6A2 as a major genetic susceptibility factor in ADHD.

Association study between single nucleotide polymorphisms in promoter region of AVPR1A and Korean autism spectrum disorders

To determine the association between arginine vasopressin receptor 1A gene (AVPR1A) and autism spectrum disorders (ASDs), we examined 3 single nucleotide polymorphisms (SNPs), namely, rs7294536, rs3759292, and rs10877969, in the promoter region of AVPR1A by using a family-based association test (FBAT) in 151 Korean trios. Our results demonstrated a statistically significant association between autism and SNPs (additive model: rs7294536, chi(2)=9.328, df=2, P=0.002; rs10877969, chi(2)=11.529, df=2, P<0.001) as well as between autism and haplotype analysis (additive model: chi(2)=14.122, df=3, P=0.003). In addition, we found that ADI-R scores calculated by using a diagnostic algorithm for failure to develop peer relationships (A2) were higher in subjects having the AA genotype than in subjects having the AG and GG genotypes of rs7294536. Thus, our study provides evidence for a possible association between these SNPs and the phenotype of ASDs.

Possible association of the alpha‐2A‐adrenergic receptor gene with response time variability in attention deficit hyperactivity disorder

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 (χ2 = 5.88, P = 0.015). In the haplotype analyses, a trend of over‐transmission of haplotype C/C was observed (χ2 = 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.

Association between the alpha-2C-adrenergic receptor gene and attention deficit hyperactivity disorder in a Korean sample.

Findings from preclinical and clinical research support the involvement of central noradrenergic dysregulation in the etiology of attention deficit hyperactivity disorder (ADHD). Previous studies have suggested that the alpha-2C-adrenergic receptor gene (ADRA2C) is associated with ADHD. The aims of this study were to examine the association between the ADRA2C (GT)n repeat polymorphism (STR marker adra2c1) and ADHD in a Korean sample. In this case-control and family-based association study, we assessed 184 ADHD probands, 150 normal controls, and 98 trios. There were no significant differences in the allele frequencies of the ADRA2C polymorphism between the ADHD and control groups (p > 0.05). The overall allele-wise transmission disequilibrium test (TDT) analysis showed statistical significance (chi2 = 19.07, p = 0.025). We found a trend for preferential transmission of the 183-bp allele (chi2 = 3.72, p = 0.054), and a significantly lower-than-expected rate of transmission of the 187-bp allele (chi2 = 6.26, p = 0.012). With regard to the temperament profiles of the Junior Temperament and Character Inventory (JTCI), the ADHD subjects with the 183/183 genotype at the ADRA2C polymorphism showed a trend toward a lower score in the Novelty Seeking (p = 0.020) profile than did those with the other genotypes. Our findings provide important evidence that the ADRA2C polymorphism is involved in the etiology of ADHD in Korean subjects. In addition, our results provide evidence that the temperament of Novelty Seeking and ADHD might share molecular genetic characteristics related to the noradrenergic system.

Neurotrophin-3 gene, intelligence, and selective attention deficit in a Korean sample with attention-deficit/hyperactivity disorder

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.

The Korean Version of the Adolescent Dissociative Experience Scale: Psychometric Properties and the Connection to Trauma among Korean Adolescents

Objective The Adolescent Dissociative Experience Scale (A-DES) is a screening measure for dissociative experience in adolescents. The present study aimed to investigate the reliability, validity and psychometric properties of the Korean version of the Adolescent Dissociative Experience Scale. Methods The Korean version of the A-DES was administered to a normative group of 371 adolescents aged 12 to 18 years and a traumatized group of 33 adolescents aged 12 to 18 years with known trauma. Results The internal consistency was excellent (Cronbachs alpha=0.91) and the test-retest correlation of the A-DES was high (r=0.99). Correlation between the A-DES and other measures of dissociation was moderate (r=0.48). There were no significant age differences in mean total A-DES scores for the normative sample, or for boys or girls separately. Nor were there any significant gender differences for any age group. The mean total score of the A-DES was significantly higher in the traumatized group than in the normative group. There was a statistically significant difference between adolescents with self-reported trauma and those without a trauma history in the normative group. Conclusion This study demonstrated that the Korean version of the A-DES is a reliable measure with excellent internal consistency and good stability over a 4-week test-retest interval with single factor structure. It can be used to screen for dissociative symptoms in Korean adolescents between the ages 12 and 18.

Genome-Wide Association Scan of Korean Autism Spectrum Disorders with Language Delay: A Preliminary Study

Objective Communication problems are a prevalent symptom of autism spectrum disorders (ASDs), which have a genetic background. Although several genome-wide studies on ASD have suggested a number of candidate genes, few studies have reported the association or linkage of specific endophenotypes to ASDs. Methods Forty-two Korean ASD patients who showed a language delay were enrolled in this study with their parents. We performed a genome-wide scan by using the Affymetrix SNP Array 5.0 platform to identify candidate genes responsible for language delay in ASDs. Results We detected candidate single-nucleotide polymorphisms (SNPs) in chromosome 11, rs11212733 (p-value=9.76×10-6) and rs7125479 (p-value=1.48×10-4), as a marker of language delay in ASD using the transmission disequilibrium test and multifactor dimensionality reduction test. Conclusion Although our results suggest that several SNPs are associated with language delay in ASD, rs11212733 we were not able to observe any significant results after correction of multiple comparisons. This may imply that more samples may be required to identify genes associated with language delay in ASD.

Affective network and default mode network in depressive adolescents with disruptive behaviors.

Aim Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors. Methods Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors. Results The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex. Conclusion Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression.

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/ hyperactivity disorder

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Emotionality’ and ‘Over-focus/euphoria’ factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest ‘Proneness to crying’ and ‘Nail biting’ item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.