Jungeun Song

The 1287 G/A polymorphism of the Norepinephrine Transporter gene (NET) is involved in Commission Errors in Korean children with Attention Deficit Hyperactivity Disorder

BackgroundPrevious evidence supports the role of noradrenergic systems in ADHD, and norepinephrine transporter (NET) is critical in regulating the noradrenergic system. The present study aimed to investigate the association between NET gene polymorphism and the performance measures of the Continuous Performance Test (CPT) in Korean ADHD children.MethodsEighty-seven children (mean age = 9.23 ± 1.99 years) with ADHD were recruited from a university hospital. Genotypes of G1287A of the NET gene (SLC6A2) were analyzed. All participants completed the CPT, with performance measures of omission errors, commission errors, reaction time and reaction standardization computed. The relationship between G1287A polymorphisms and CPT performance measures was examined.ResultsThere were 46 subjects with the G/G genotype, 35 subjects with the G/A genotype and 6 subjects with the A/A genotype. Among the three groups, there were no significant differences in the performance of CPTs. When dichotomized according to whether the subjects have the rare allele or not, subjects with the homozygous G/G genotype showed significantly lower commission errors compared to those without G/G genotypes (by independent T-test, t = -2.18, p = 0.026).DiscussionOur study found a significant association between commission errors of the CPT and the G1287A genotype of the NET gene in Korean ADHD children. These findings suggest a protective role of the G/G genotype of the NET polymorphisms in the deficits of response inhibition in ADHD children.

Norepinephrine transporter gene (SLC6A2) is involved with methylphenidate response in Korean children with attention deficit hyperactivity disorder.

The purpose of this study was to investigate the association between the methylphenidate (MPH) response and the norepinephrine transporter (NET) gene polymorphisms in Korean children with attention deficit hyperactivity disorder (ADHD). One hundred and fourteen children with ADHD (mean age 9.08±1.94 years) were recruited from a child psychiatric clinic in South Korea. The genomic DNA was extracted from the blood lymphocyte. Patients were administered MPH for 8 weeks. Good response was defined as a decrease of more than 50% from the baseline ADHD rating scale-IV scores or Clinical Global Impression-Severity score was 1 or 2 after treatment. We compared the MPH response according to the genotype of G1287A of the NET gene (SLC6A2). In patients with G/G genotype, 41 patients (71.9%) showed good response and 16 patients (28.1%) showed poor response when it was measured by the ADHD rating scale-IV. In comparison, 23 patients (46.0%) with G/A genotype and four patients (57.1%) with A/A genotype showed good response (P=0.018, by the Fishers exact test). When we compared the response of MPH between patients with G/G genotype and those without G/G genotype, 41 patients (71.9%) with G/G genotype showed good response, whereas only 27 patients (46.4%) without G/G genotype showed good response. [Pearson &khgr;2=7.143, degrees of freedom (df)=1, P=0.008]. Our study found a significant association between the G1287A genotype of the NET gene and the MPH response in Korean children with ADHD. These findings support the significant role of the NET gene in ADHD treatment with MPH.

The Structure of Co-Occurring Bullying Experiences and Associations with Suicidal Behaviors in Korean Adolescents.

Objective This study had two main goals: to examine the structure of co-occurring peer bullying experiences among adolescents in South Korea from the perspective of victims and to determine the effects of bullying on suicidal behavior, including suicidal ideation and suicide attempts, among adolescents. Method This study used data gathered from 4,410 treatment-seeking adolescents at their initial visits to 31 local mental health centers in Gyeonggi Province, South Korea. The structure of peer bullying was examined using latent class analysis (LCA) to classify participants’ relevant experiences. Then, a binomial logistic regression adjusted by propensity scores was conducted to identify relationships between experiences of being bullied and suicidal behaviors. Results The LCA of experiences with bullying revealed two distinct classes of bullying: physical and non-physical. Adolescents who experienced physical bullying were 3.05 times more likely to attempt suicide than those who were not bullied. Victims of (non-physical) cyber bullying were 2.94 times more likely to attempt suicide than were those who were not bullied. Conclusions Both physical and non-physical bullying were associated with suicide attempts, with similar effect sizes. Schools and mental health professionals should be more attentive than they currently are to non-physical bullying.

Association of SNAP-25, SLC6A2, and LPHN3 with OROS methylphenidate treatment response in attention-deficit/hyperactivity disorder.

ObjectivesOur study aimed to identify the association of norepinephrine transporter gene (SLC6A2), synaptosomal-associated protein of the 25-kDa gene (SNAP-25), and latrophilin 3 gene (LPHN3) with osmotic-controlled release oral delivery system methylphenidate (OROS MPH) treatment response. MethodsOne hundred thirty-nine children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were recruited. We selected rs192303, rs3785143 in SLC6A2; rs3746544 (1065 T>G) in SNAP-25; and rs6551665, rs1947274, and rs2345039 in LPHN3 to examine the association of OROS MPH treatment response with each single nucleotide polymorphism. We first defined good response group when the Korean version of the ADHD rating scale score at 8 weeks was decreased for more than 50% of baseline scores and compared genotype frequencies in good response group with poor group. Second, we defined it when the Clinical Global Impression-Improvement score at 8 weeks was 1 or 2, and we also analyzed the genotype frequencies. ResultsThere was a significant association between the 1065 T>G of SNAP-25 gene and OROS MPH response, with the good response group defined by the Korean version of ADHD rating scale scores; 33.3% of the subjects with GG genotype showed a good response, whereas 74.7% of those with TT genotype and 72.5% of those with TG genotype showed good responses (P=0.034). SLC6A2 rs192303 was related with OROS MPH treatment response when we defined good treatment response by Clinical Global Impression-Improvement (P=0.009). ConclusionsOur study suggested that SNAP-25 gene and SLC6A2 were involved with OROS MPH response.

Predictors of Suicide Attempts in Clinically Depressed Korean Adolescents

We examined predictors of suicide attempts in clinically depressed adolescents in Korea and gender differences in suicidal behavior. In total, 106 adolescents diagnosed with depressive disorder were recruited in South Korea. We assessed various variables that might affect suicide attempts, and used a structured interview for the diagnosis of depression and comorbidities and to evaluate suicidality. Demographic and clinical characteristics of the subjects were compared between suicide attempt and non-suicide attempt groups and we examined significant predictors of suicide attempts. Gender differences in suicidal ideation and suicidal behavior were also analyzed. Among 106 depressed participants, 50 (47.2%) adolescents were classified in the suicide attempt group. Generally, the suicide attempt and non-suicide attempt group shared similar clinical characteristics. The suicide attempt group had more females, more major depressive disorder diagnoses, more depressive episodes, and higher suicidal ideation than the non-suicide attempt group. Suicidal ideation was the only significant predictor of suicidal attempt, regardless of gender. Higher suicidal ideation frequency scores and more non-suicidal self-injurious behaviors were shown in the female suicide attempt group than the male suicide attempt group. It is recommended that suicidal ideation be assessed regularly and managed rigorously to decrease suicide risks in depressive adolescents.

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Cross-Cultural Aspect of Behavior Assessment System for Children-2, Parent Rating Scale-Child: Standardization in Korean Children

Purpose Our study aimed to examine psychometric properties and cross-cultural utility of the Behavior Assessment System for Children-2, Parent Rating Scale-Child (BASC-2 PRS-C) in Korean children. Materials and Methods Two study populations were recruited: a general population sample (n=2115) of 1st to 6th graders from 16 elementary schools and a clinical population (n=219) of 6–12 years old from 5 child psychiatric clinics and an epidemiological sample of autism spectrum disorder. We assessed the validity and reliability of the Korean version of BASC-2 PRS-C (K-BASC-2 PRS-C) and compared subscales with those used for US populations. Results Our results indicate that the K-BASC-2 PRS-C is a valuable instrument with reliability and validity for measuring developmental psychopathology that is comparable to those in Western population. However, there were some differences noted in the mean scores of BASC-2 PRS-C between Korean and US populations. Conclusion K-BASC-2 PRS-C is an effective and useful instrument with psychometric properties that permits measurement of general developmental psychopathology. Observed Korean-US differences in patterns of parental reports of childrens behaviors indicate the importance of the validation, standardization and cultural adaptation for tools assessing psychopathology especially when used in populations different from those for which the instrument was originally created.

The social responsiveness scale in relation to DSM IV and DSM5 ASD in Korean children.

The Social Responsiveness Scale (SRS) is an autism rating scales in widespread use, with over 20 official foreign language translations. It has proven highly feasible for quantitative ascertainment of autistic social impairment in public health settings, however, little is known about the validity of the reinforcement in Asia populations or in references to DSM5. The current study aims to evaluate psychometric properties and cross‐cultural aspects of the SRS‐Korean version (K‐SRS).The study subjects were ascertained from three samples: a general sample from 3 regular education elementary schools (n=790), a clinical sample (n=154) of 6–12‐year‐olds from four psychiatric clinics, and an epidemiological sample of children with ASD, diagnosed using both DSM IV PDD, DSM5 ASD and SCD criteria (n=151). Their parents completed the K‐SRS and the Autism Spectrum Screening Questionnaire(ASSQ). Descriptive statistics, correlation analyses and principal components analysis (PCA) were performed on the total population. Mean total scores on the K‐SRS differed significantly between the three samples. ASSQ scores were significantly correlated with the K‐SRS T‐scores. PCA suggested a one‐factor solution for the total population.Our results indicate that the K‐SRS exhibits adequate reliability and validity for measuring ASD symptoms in Korean children with DSM IV PDD and DSM5 ASD. Our findings further suggest that it is difficult to distinguish SCD from other child psychiatric conditions using the K‐SRS.This is the first study to examine the relationship between the SRS subscales and DSM5‐based clinical diagnoses. This study provides cross‐cultural confirmation of the factor structure for ASD symptoms and traits measured by the SRS. Autism Res 2016, 9: 970–980.