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      • Norepinephrine Genes Predict Response Time Variability and Methylphenidate-Induced Changes in Neuropsychological Function in Attention Deficit Hyperactivity Disorder

        Kim, Bung-Nyun,Kim, Jae-Won,Cummins, Tarrant D.R.,Bellgrove, Mark A.,Hawi, Ziarih,Hong, Soon-Beom,Yang, Young-Hui,Kim, Hyo-Jin,Shin, Min-Sup,Cho, Soo-Churl,Kim, Ji-Hoon,Son, Jung-Woo,Shin, Yun-Mi,Chun Lippincott Williams Wilkins, Inc. 2013 JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Vol.33 No.3

        ABSTRACT: Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)–OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

      • KCI등재

        Cognitive and Behavioral Outcomes of School-aged Children Born Extremely Preterm: a Korean Single-center Study with Long-term Follow-up

        Kim Eun Sun,Kim Ee-Kyung,Kim Sae Yun,Song In Gyu,Jung Young Hwa,Shin Seung Han,Kim Han-Suk,Kim Johanna Inhyang,Kim Bung Nyun,Shin Min-Sup 대한의학회 2021 Journal of Korean medical science Vol.36 No.39

        Background: School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. Methods: A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used. Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. Results: The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001). In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. Conclusion: This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems were not different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

      • A Mobile Videoconference-Based Intervention on Stress Reduction and Resilience Enhancement in Employees: Randomized Controlled Trial

        Kim, Johanna Inyang,Yun, Je-Yeon,Park, Heyeon,Park, Suk-Young,Ahn, Youngsheen,Lee, Hansol,Kim, Tae-Kwon,Yoon, Sooran,Lee, Young-Joon,Oh, Sohee,Denninger, John W,Kim, Bung-Nyun,Kim, Jeong-Hyun JMIR Publications 2018 Journal of medical Internet research Vol.20 No.10

        <P><B>Background</B></P><P>Videoconferencing-based treatments have shown great potential in increasing engagement and compliance by decreasing the barriers of time and distance. In general, employees tend to experience a lot of stress, but find it difficult to visit a clinic during office hours.</P><P><B>Objective</B></P><P>The purpose of this study was to investigate the effectiveness of a mobile videoconference-based intervention for stress reduction and resilience enhancement in employees.</P><P><B>Methods</B></P><P>In total, 81 participants were randomly allocated to one of the three conditions: mobile videoconferencing, in-person, and self-care; of these, 72 completed the study. All participants underwent assessment via self-reported questionnaires before, immediately after, and 1 month after the intervention. Intervention lasted for 4 weeks and consisted of elements of cognitive behavioral therapy, positive psychology, and meditation. Changes in clinical variables regarding stress and resilience across time were compared between treatment conditions.</P><P><B>Results</B></P><P>There were significant condition × time effects on variables measuring perceived stress, resilience, emotional labor, and sleep, demonstrating significantly differential effects across time according to treatment condition. Moreover, there were significant effects of condition on perceived stress and occupational stress. There were no significant differences in any variable between the mobile videoconferencing and in-person conditions at 1 month after the intervention.</P><P><B>Conclusions</B></P><P>Results indicate that both mobile videoconferencing and in-person interventions were comparably effective in decreasing stress and enhancing resilience. Further studies with a larger sample size and a longer follow-up period are warranted to investigate the long-term effect of mobile videoconferencing interventions.</P><P><B>Trial Registration</B></P><P>ClinicalTrials.gov identifier NCT03256682; https://clinicaltrials.gov/ct2/show/NCT03256682 (Archived by WebCite at http://www.webcitation.org/71W77bwnR)</P>

      • SCISCIESCOPUS

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

        Kim, Johanna Inhyang,Hong, Yun-Chul,Shin, Choong Ho,Lee, Young Ah,Lim, Youn-Hee,Kim, Bung-Nyun Academic Press 2017 Environmental research Vol.156 No.-

        <P><B>Abstract</B></P> <P>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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The negative effects of phthalate exposure on attention and intelligence in school-age children are independent of each other. </LI> <LI> Childhood, but not maternal phthalate exposure was found to affect both attention and intelligence. </LI> <LI> Phthalate metabolites have a significant association with inattention and deficit in sustained attention. </LI> </UL> </P>

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

        Kim, Johanna Inhyang,Kim, Jae-Won,Lee, Jong-Min,Yun, Hyuk Jin,Sohn, Chul-ho,Shin, Min-Sup,Kim, Bongseog,Chae, Jonghee,Roh, Jaewoo,Kim, Bung-Nyun Elsevier 2018 Progress in neuro-psychopharmacology & biological Vol.82 No.-

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>The dopamine receptor D2 receptor (<I>DRD2</I>) 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, <I>DRD2</I>, and lead exposure. We examined the interaction effects of <I>DRD2</I> rs1800497 and lead exposure on the cortical thickness of the frontal lobe in patients with ADHD.</P> <P><B>Methods</B></P> <P>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 <I>DRD2</I> and lead exposure on the cortical thickness of 12 regions of interest in the frontal lobe were examined by multivariable linear regression analyses.</P> <P><B>Results</B></P> <P>When we investigated the <I>DRD2</I> ×lead effects in the ADHD and HC groups separately, significant <I>DRD2</I> ×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.</P> <P><B>Conclusions</B></P> <P>The present findings demonstrated significant interaction effects of <I>DRD2</I> 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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The dopamine receptor D2 receptor (<I>DRD2</I>) gene and lead exposure contribute to the pathophysiology of ADHD. </LI> <LI> Previous study results indicate an overlap in the neural correlates of ADHD, <I>DRD2</I>, and lead exposure in the prefrontal cortex. </LI> <LI> We found significant interactions between <I>DRD2</I> and lead exposure on the cortical thickness of the frontal lobe in ADHD patients. </LI> <LI> This study highlights the need for consideration of gene-environment interaction when conducting studies regarding dopamine-related genes. </LI> </UL> </P>

      • SCOPUSKCI등재

        The Effect of Prenatal Cadmium Exposure on Attention-deficit/Hyperactivity Disorder in 6-Year-old Children in Korea

        Kim, Woosung,Jang, Yoonyoung,Lim, Youn-Hee,Kim, Bung-Nyun,Shin, Choong Ho,Lee, Young Ah,Kim, Johanna Inhyang,Hong, Yun-Chul The Korean Society for Preventive Medicine 2020 예방의학회지 Vol.53 No.1

        Objectives: Prenatal cadmium (Cd) exposure may be associated with attention-deficit/hyperactivity disorder (ADHD) in children. Therefore, the objective of this study was to examine the relationship between Cd exposure during gestation and ADHD at 6 years of age. Methods: As part of an ongoing cohort study (the Environment and Development of Children study), 479 mother-child pairs from Seoul, Korea were included for analysis between 2008 and 2011. The whole blood concentration of Cd was analyzed using atomic absorption spectrophotometry. The parents were surveyed about ADHD behaviors in their children at age 6. Multivariable linear regression models were used to investigate the relationship between prenatal exposure to Cd and ADHD at 6 years of age. Results: Increased prenatal Cd concentrations were associated with increased scores for ADHD for girls, but not for boys, at age 6. A 2-fold increase in the prenatal Cd level was significantly associated with a 22.3% (95% confidence interval, 11.6 to 34.1) increase in ADHD in girls at 6 years of age, as indicated by the linear regression model. Conclusions: Our results identified significant associations between prenatal Cd exposure and ADHD scores in 6-year-old girls.

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

        Kim, Johanna Inhyang,Kang, Yun-Hyong,Lee, Jong-Min,Cha, Jungho,Park, Yeong-Hun,Kweon, Kuk-Ju,Kim, Bung-Nyun Elsevier 2018 Progress in neuro-psychopharmacology & biological Vol.86 No.-

        <P><B>Abstract</B></P> <P>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.</P> <P>Trial registration: ClinicalTrials.gov identifier: NCT02670876 </P> <P><B>Highlights</B></P> <P> <UL> <LI> School bullying is a universal phenomenon that has significant negative effects on mental health for both the perpetrator and victim. </LI> <LI> We conducted cognitive-behavioral therapy targeting cognitive distortions related to externalizing problems commonly found in bullies. </LI> <LI> The purpose of this study was to investigate the effects and neural correlates of this intervention on externalizing problems. </LI> <LI> We found a positive effect on externalizing problems and this was associated with changes in spontaneous neural activity in related brain regions. </LI> <LI> Further studies that include large homogeneous samples and well-controlled designs are warranted. </LI> </UL> </P>

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