Johanna Inhyang Kim

The metabotropic glutamate receptor subtype 7 rs3792452 polymorphism is associated with the response to methylphenidate in children with attention-deficit/hyperactivity disorder.

OBJECTIVE The purpose of this study was to investigate the association between the metabotropic glutamate receptor subtype 7 (mGluR7) gene (GRM7) polymorphism and treatment response to methylphenidate in Korean children with attention-deficit/hyperactivity disorder (ADHD). METHODS We enrolled 175 medication-naïve children with ADHD in an open-label 8 week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical Global Impressions (CGI) Scale and the parent version of the ADHD Rating Scale-IV (ADHD-RS) before and after treatment. RESULTS After the 8 week course of methylphenidate, children with the GRM7 rs37952452 polymorphism G/A genotype had a more pronounced response rate to the treatment than did children with the G/G genotype according to the ADHD-RS scores (72.2% vs. 55.4%, respectively; p=0.011) and the more stringent standard of combined ADHD-RS and CGI-Improvement (CGI-I) scores (50.0% vs. 35.3%, respectively; p=0.044). CONCLUSIONS The present study suggests that the GRM7 rs37952452 polymorphism may play a role in the treatment response to methylphenidate in children with ADHD. Further studies to evaluate the association between glutamate genes and treatment response to methylphenidate in children with ADHD, including a replication of our findings using a control or comparative group in a larger sample, are warranted.

The effects of maternal and children phthalate exposure on the neurocognitive function of 6-year-old children

ABSTRACT The primary purpose of this study was to investigate the effects of phthalate exposure on the intelligence and attentional performance of 6‐year old children when adjusting each other as covariates. We also investigated the differential effects of phthalate exposure on the intelligence and attention according to exposure period (maternal or children). Urine concentrations of mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate (MEHHP), mono‐(2‐ethyl‐5‐oxohexyl) phthalate (MEOHP), and mono‐n‐butyl phthalate (MBP) were analyzed. Multivariable linear regression models were used to investigate the relationship between exposure to various phthalates with IQ scores and continuous performance test (CPT) variables. There were robust associations between child MEHHP and MEOHP levels with full scale IQ (FSIQ) even after adjusting for demographic variables and CPT scores (MEHHP −9.27, 95% CI: −17.25, −1.29; MEOHP −9.83, 95% CI: −17.44, −2.21). Child MEHHP and MEHOP levels negatively affected omission errors (MEHHP −20.36, 95% CI: −34.17, −6.55; MEOHP −18.93, 95% CI: −32.58, −5.28) and the response time variability (MEHHP −21.07, 95% CI: −39.04, −3.10; MEOHP −20.41, 95% CI −38.14, −2.69) of the CPT after adjusting for demographic variables and IQ. Maternal phthalate exposure had no effects on IQ or CPT variables. These results suggest that children phthalate exposure, but not maternal exposure, has an adverse effect on IQ and attentional performance, and these associations were found to be independent of each other. HighlightsThe negative effects of phthalate exposure on attention and intelligence in school‐age children are independent of each other.Childhood, but not maternal phthalate exposure was found to affect both attention and intelligence.Phthalate metabolites have a significant association with inattention and deficit in sustained attention.

Interaction between DRD2 and lead exposure on the cortical thickness of the frontal lobe in youth with attention-deficit/hyperactivity disorder

Background: The dopamine receptor D2 receptor (DRD2) gene and lead exposure are both thought to contribute to the pathophysiology of attention‐deficit/hyperactivity disorder (ADHD). ADHD is characterized by delay in brain maturation, most prominent in the prefrontal cortex (PFC). The D2 receptor is also mainly located in the PFC, and animal studies show that lead exposure affects the dopaminergic system of the frontal lobe, indicating an overlap in neural correlates of ADHD, DRD2, and lead exposure. We examined the interaction effects of DRD2 rs1800497 and lead exposure on the cortical thickness of the frontal lobe in patients with ADHD. Methods: A 1:1 age‐ and gender‐matched sample of 75 participants with ADHD and 75 healthy participants was included in the analysis. The interaction effects of DRD2 and lead exposure on the cortical thickness of 12 regions of interest in the frontal lobe were examined by multivariable linear regression analyses. Results: When we investigated the DRD2 × lead effects in the ADHD and HC groups separately, significant DRD2 × lead effects were found in the ADHD group, but not in the healthy control group in multiple ROIs of the frontal lobe. There was a significant negative correlation between the cortical thickness of the right superior frontal gyrus and inattention scores. Conclusions: The present findings demonstrated significant interaction effects of DRD2 and lead exposure on the cortical thickness of the frontal lobe in ADHD. Replication studies with larger sample sizes, using a prospective design, are warranted to confirm these findings. HighlightsThe dopamine receptor D2 receptor (DRD2) gene and lead exposure contribute to the pathophysiology of ADHD.Previous study results indicate an overlap in the neural correlates of ADHD, DRD2, and lead exposure in the prefrontal cortex.We found significant interactions between DRD2 and lead exposure on the cortical thickness of the frontal lobe in ADHD patients.This study highlights the need for consideration of gene‐environment interaction when conducting studies regarding dopamine‐related genes.

Interaction effects of GIT1 and DRD4 gene variants on continuous performance test variables in patients with ADHD

The G protein‐coupled receptor kinase interacting protein 1 gene (GIT1) has been proposed to be a risk gene for attention deficit hyperactivity disorder (ADHD), and it regulates the endocytosis of G protein‐coupled receptors like dopamine receptors. The purpose of this study was to investigate the interaction effects of GIT1 and dopamine receptor D4 (DRD4) gene variants on variables of the continuous performance test (CPT).

Reliability and Validity of a New Comprehensive Tool for Assessing Challenging Behaviors in Autism Spectrum Disorder

Objective The purpose of this study was to examine the validity and reliability of the Korean Comprehensive Scale for the Assessment of Challenging Behavior in Developmental Disorders (K-CSCB). Methods In total, the parents of 189 patients with autism spectrum disorder (ASD) and 168 controls completed the K-CSCB, the Behavior Problems Inventory (BPI) and Child Behavior Checklist (CBCL). The reliability and validity of the K-CSCB was investigated. Results The K-CSCB was found to be a reliable instrument (Cronbachs α=0.97). There was a significant difference between the ASD and control groups in all subscale scores. Scores on the K-CSCB subscales were significantly correlated with those on the BPI and CBCL. The diagnostic validity was 97.7%, and the cut-off score with the highest sensitivity and specificity was 12.5 points. Conclusion The K-CSCB is the first tool in Korean to assess problematic behavior in individuals with ASD, and this study shows that it is a valid and reliable instrument. We expect the K-CSCB to be widely used in clinical and research settings.

Resting-state functional magnetic resonance imaging investigation of the neural correlates of cognitive-behavioral therapy for externalizing behavior problems in adolescent bullies

&NA; The purpose of this study was to investigate the neural correlates of cognitive‐behavioral therapy (CBT) for externalizing behavior problems in perpetrators of school bullying using assessments of brain activity and behavior. Twenty‐five adolescent bullies participated in an 8‐session intervention. Prior to and after participation, 24 adolescents were evaluated using the Child Behavior Checklist (CBCL) and 23 completed resting‐state functional magnetic resonance imaging. Changes in the fractional amplitude of low‐frequency fluctuations (fALFF) and scores on the CBCL were analyzed. We also compared the identified changes into 2 groups (low and high delinquency) differentiated by a cutoff of 65 points on the delinquency subscale of the CBCL. Following the intervention, participants exhibited improvement in the subscores of the CBCL and decreases in the fALFF of the inferior parietal lobule, lingual, interior frontal and middle occipital gyrus. A positive correlation was observed between changes in the CBCL externalizing behavior scores and fALFF of the inferior frontal gyrus. The high delinquency group showed a greater decrease in delinquency and externalizing CBCL subscores across time than did the low delinquency group. The high delinquency group had more areas that showed change in fALFF post‐intervention than did the low delinquency group. A positive correlation was observed between changes in the CBCL delinquency scores and fALFF of the precentral gyrus in the high delinquency group. The results indicate that this CBT for externalizing behavior problems in bullies had more positive effects on delinquent behavior in adolescents with high levels of delinquency, and these changes were associated with functional changes in brain activity. Trial registration: ClinicalTrials.gov identifier: NCT02670876 HighlightsSchool bullying is a universal phenomenon that has significant negative effects on mental health for both the perpetrator and victim.We conducted cognitive‐behavioral therapy targeting cognitive distortions related to externalizing problems commonly found in bullies.The purpose of this study was to investigate the effects and neural correlates of this intervention on externalizing problems.We found a positive effect on externalizing problems and this was associated with changes in spontaneous neural activity in related brain regions.Further studies that include large homogeneous samples and well‐controlled designs are warranted.

Interaction of DRD4 Methylation and Phthalate Metabolites Affects Continuous Performance Test Performance in ADHD

Objective: We investigated the interaction effect between the methylation of dopamine receptor D4 (DRD4) and phthalate exposure in ADHD on continuous performance test (CPT) variables. Method: Urine concentrations of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MBP) were tested. The methylation status was analyzed for CpG sites of DRD4. Multivariable linear regression models were applied to investigate the interaction effects of methylation and phthalate levels. Results: There was a significant interaction effect of the methylation of CpG26 and CpG28 with the MEHHP level on omission errors in ADHD patients, but not in controls. The post hoc analysis revealed a significant correlation between the MEHHP concentration and omission errors in the methylated group, but not in the unmethylated group. Conclusion: The interaction between the methylation status of CpG sites of DRD4, particularly CpG26 and CpG28, and phthalate metabolite levels affects the attention level in ADHD patients.

Moderating effects of depressive symptoms on the relationship between problematic use of the Internet and sleep problems in Korean adolescents

AbstractsBackgroundAdolescence is a period of marked sleep pattern changes and sleep problems, which may result from both endogenous and exogenous factors. Among the various factors affecting adolescent sleep, depression and problematic Internet use (PIU) have received considerable attention. We examined if there is a different PIU effect on sleep between depressed group and non-depressed groups.MethodsData for a total of 766 students’ between 7th and 11th grades were analyzed. We assessed various variables related sleep to problems and depression and compared those variables between an adolescent group with problematic Internet use (PIUG) and an adolescent group with normal Internet use (NIUG).ResultsOne hundred fifty two participants were classified as PIUG, and 614 were classified as NIUG. Compared with the NIUG, the members of the PIUG were more prone to insomnia, excessive daytime sleepiness and sleep-wake behavior problems. The PIUG also tended to include more evening types than the NIUG. Interestingly, the effect of Internet use problems on sleep problems appeared to be different according to the presence or absence of the moderating effect of depression. When we considered the moderating effect of depression, the effect of Internet use problems on sleep-wake behavior problems, insomnia and excessive daytime sleepiness increased with increasing Young’s Internet Addiction Scale (IAS) scores in the non-depressed group. However, in the depressed group, the effects of Internet use problems on sleep-wake behavior problems and insomnia did not change with increasing Internet use problems, and the effect of Internet use problems on excessive daytime sleepiness was relatively decreased with increasing Internet use problems in the depressed group.ConclusionsThis study demonstrated that the effect of PIU on sleep presented differently between the depressed and non-depressed groups. PIU is associated with poorer sleep in non-depressed adolescents but not in depressed adolescents. This finding might be observed because PIU may be the biggest contributor to sleep problems in the problematic Internet user without depression, but in the problematic Internet user with depression, depression might be a more important contributor to sleep problems; thus, the influence of PIU on sleep effect might be diluted.