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Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS(®) (Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS(®) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS(®) for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS(®) Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS(®) treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS(®) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS(®) treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD.

ObjectiveaaWe aimed to investigate the neurocognitive and behavioral endophenotypes of premorbid mood disorder. We compared intelligence, neuropsychological functioning, and behavioral problems among three groups: 1) a high-risk group [attention-deficit hyperac tivity disorder (ADHD) children of parents with a history of a mood disorder], 2) a low-risk group (ADHD children of parents without a history of a mood disorder), and 3) normal comparison subjects. MethodsaaWe used the Korean Educational Development Institute Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R), the Stroop Color Word Interference Test (Stroop), the Wisconsin Card Sorting Test (WCST), and the Rey-Osterrieth Complex Figure Test (RCFT) as neurocognitive measures, and we used the Child Behavior Checklist (CBCL) as a behavioral measure. Performance on these neuropsychological tests and score on the CBCL of 18 high-risk children were compared to those of 20 low-risk children and 24 healthy children. We also assessed the children’s current mood state and familial functioning to control for the confounding effects of these variables. ResultsaaCompared to low-risk and healthy children, high-risk children were impaired on the Picture Completion and Stroop Word subtest and showed higher scores on the CBCL subscales representing internalizing symptoms. These significant group differences per sisted even after adjustment for the children’s current mood state and familial functioning. ConclusionaaNeuropsychological deficits in the offspring of parents with a mood disorder may be associated with the current mood state rather than with innate characteristics, while their internalizing symptoms may partially stem from innate characteristics that are endophenotypes of a premorbid mood disorder. Psychiatry Investig 2014;11:65-75 Key Wordsaa Mood disorder, Attention deficit hyperactivity disorder, Neuropsychology, Endophenotype, High-risk, Offspring.

Objective 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). Methods Four hundred and ninety-five children and adolescents (391 boys and 104 girls), aged 7 to 18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for ADHD, were recruited at 48 psychiatric outpatient clinics across South Korea. Children's symptoms, parenting stress, and parental depression were assessed at baseline, week 4, and week 8 of MPH-OROS treatment using the Korean version of the DuPaul's ADHD Rating Scale (ARS), the Beck's Depression Inventory (BDI), and the Parenting Stress Index, Short Form (PSI-SF). Results We found significantly decreased scores of ARS, parental BDI, and PSI-SF from baseline to week 4 and from week 4 to week 8. Also, there were positive correlations among baseline PSI-SF, ARS, and BDI scores. The changes in BDI and ARS scores were significantly associated with the PSI score changes, accounting for 20.1% and 10.0%, respectively. Conclusions We suggest that the increased parenting stress and depression in parents of children and adolescents with ADHD can be improved following the treatment with MPH-OROS. Copyright © 2013 John Wiley & Sons, Ltd.

BACKGROUND: The lethality of the suicide method is a strong risk factor for completed suicide. We examined whether the annual change in the pattern of suicide methods was related to the annual change in suicide rates among adolescents in South Korea and the United States. METHODS: We analyzed annual data for the 2000-2009 period for South Korea and the 2000-2008 period for the United States to examine time trends in the suicide rates and suicide methods of adolescents aged 10-19 years in two countries. Data on suicide methods were obtained from the World Health Organization (WHO) mortality database. RESULTS: Suicide rates among adolescents in the United States have remained relatively steady since 2000, whereas the suicide among Korean adolescents has increased. Between 2000 and 2009, the most common suicide method among Korean adolescents was jumping for boys and girls, whereas it was hanging for girls and firearms for boys in the United States. Along with the annual increase in suicide rates in South Korea, the incidences of jumping among males and hanging (and recently jumping) among females have increased steadily, whereas suicide by self-poisoning steadily decreased. In the United States, between 2000 and 2008, the proportion of suicides committed by hanging increased, whereas those committed using firearms steadily decreased, particularly among adolescent females. CONCLUSIONS: These findings suggest that the increased use of lethal suicide methods is reflected in the increase in suicide rates in Korean adolescents. The most fruitful approach to addressing the rises in jumping suicides among Korean adolescents and hanging suicides among adolescents in the United States may be through population-based initiatives to reduce the physical availability (e.g., limiting access to or fencing off tall structures) and the social acceptability (e.g., effective and responsible regulations for reporting suicide) of these methods. Language: en

Manganese (Mn) is neurotoxic at high concentrations. However, Mn is an essential element that can protect against oxidative damage; thus, extremely low levels of Mn might be harmful. Our aim was to examine whether either high or low environmental Mn exposure is related to academic and attention function development among school-aged children. This cross-sectional study included 1089 children 8–11 years of age living in five representative areas in South Korea. Blood Mn, blood lead, and urine cotinine were measured. We assessed IQ with the Wechsler Abbreviated Scale of Intelligence; attention with a computerized continuous performance test called the Attention-deficit/hyperactivity disorder (ADHD) Diagnostic System (ADS), the Korean version of the Stroop Color-Word Test, the Children's Color Trails Test (CCTT), and the ADHD Rating Scale; academic functions with the Learning Disability Evaluation Scale (LDES); and emotional and behavioral problems with the Korean version of the Child Behavior Checklist (CBCL). We further assessed the presence of ADHD using a highly structured diagnostic interview, the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The median blood concentration of Mn was 14.14 µg/L. We observed a nonlinear association between the CCTT2 completion time and the CPT commission error ( F =3.14, p =0.03 and F =4.05, p =0.01, respectively). We divided the data into three groups: lower ( 21.453 µg/L) and middle 90th percentile to determine whether a lack or overload of Mn could cause adverse effects. After adjusting for urine cotinine, blood lead, children's IQ, and other potential confounders, the high Mn group showed lower scores in thinking ( B =−0.83, p =0.006), reading ( B =−0.93, p =0.004), calculations ( B =−0.72, p =0.005), and LQ ( B =−4.06, p =0.006) in the LDES and a higher commission error in the CPT ( B =8.02, p =0.048). The low Mn group showed lower color scores in the Stroop test ( B =−3.24, p =0.040). We found that excess Mn in children is associated with lower scores of thinking, reading, calculation, and LQ in the LDES and higher scores of commission error in the ADS test. In contrast, lower Mn in children is associated with lower color scores in the Stroop test. The findings of this cross-sectional study suggest that excess exposure or deficiency of Mn can cause harmful effects in children.

This study evaluated the family-based genetic association between autism spectrum disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios (dominant model Z = 2.598, P = 0.009, P FDR = 0.045). We found a statistically significant allele transmission or association in terms of the rs6269 SNP in the ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269 demonstrated significant evidence of an association with ASDs (additive model rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P FDR = 0.040). Thus, an association may exist between the variants of the COMT gene and the occurrence of ASDs in Koreans.

Autism spectrum disorders (ASD) encompass a range of neurodevelopmental conditions that are clinically and etiologically very heterogeneous. ASD is currently diagnosed entirely on behavioral criteria, but intensive research efforts are focused on identifying biological markers for disease risk and early diagnosis. Here, we discuss recent progress toward identifying biological markers for ASD and highlight specific challenges as well as ethical aspects of translating ASD biomarker research into the clinic.

The authors examined the association between the MspI C/G and DraI C/T genotypes of the α2A-adrenergic receptor gene and white-matter connectivity and attentional performance before and after medication in 53 children with attention-deficit hyperactivity disorder. Subjects who carried the T allele at the DraI polymorphism showed fewer changes in the mean commission error scores after 8 weeks of medication and decreased fractional anisotropy (FA) values in the right middle frontal cortex than subjects without the T allele. Subjects with the C allele at the MspI polymorphism showed decreased FA values in the right postcentral gyrus than subjects without.

Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, KoreaMany child actors have appeared in various movies as the Korean film industry continues to evolve. As more children appear in violent and raunchy scenes, there are more concerns about the movie’s effect on child actors. In some Western countries, many strategies have been developed for child actors, but for the Korean movie industry, the conditions are still poor for them. Al-though children who enter the concrete operational period are able to think logically and systematically, they are yet limited by their experiences. Adolescents in the formal operational period try to deal with all of the possibilities and assumptions logically and systematically with freedom from realistic contents and experiences. This period is very important because adolescents be-come more sensitive to others’ feelings and they should develop their ego identity. Several studies have reported the indirect ex-periences through media including how the movie affected children and adolescents negatively. Depending on the individual’s morality, judgment and emotional status, these effects were variable and inconsistent and could be relieved by several interventions. We could anticipate much bigger emotional effect on child actors who are acting directly and then are confronting themselves in the scene. Therefore, we suggest that the emotional effects of the movies on child actors can be managed properly by considering children’s cognitive ability and emotional status, and establishing protective strategies before they are exposed to problematic scenes. Of course, it should be followed by evaluating them after the exposure and with follow-up management, if necessary.

This study was conducted to evaluate the psychological changes and influences of child actors depending on their role. First, we met the film producer of Dogani and discussed about the filming condition. Second, we visited filming locations during the filming of Neighborhood, when shooting of parts involving the female child actor was taking place and evaluated the emotional states of the child actor before and after she played her role. Third, we interviewed various people of the movie industry, which included adult actors, directors, a professor of films and broadcasting who was a former child actor and a scriptwriter. In case of the film Dogani, the production crew provided enough care and protection and we concluded that child actors had no psychologi - cal sequelae. After interviewing the child actor and visiting filming locations, we confirmed that the child actor was not influ - enced by playing certain roles. In addition, after interviewing various people related to filming, we thought that child actors might not have psychological sequelae related to the character played. To the best of our knowledge, this is the first study about influences of the playing character for child actors. We concluded that playing certain roles would not have negative effects on child actors.

Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, KoreaPsychological resilience in children preventing them from being overwhelmed by traumatic events and nurture their healthy development is universal and powerful. Movies about fairy tales provide children with the notion of the existence of the power and various manifestations. Even though the traumatic event affects the development of the child, with a good supporting system and by providing healthy internal and external factors to reconstruct the event, the traumatized child may accept the event objec-tively, develop the healthier part of the ego, and even sublimate the traumatic events. As the children participate in movies or plays, several protectors can be devised. The child prepares the role under a “promise” of virtual reality, performs the role recog-nizing that the traumatic event is not real, and returns to real life as the role or play ends. When these protectors are provided, it is considered that resilience can function properly and the role does not have a negative influence on the development of a child.

Child labor is being recognized as the key issue of human rights, and the International Labor Organization and the Convention on the Rights of the Child emphasize that children are individuals with dignity and rights. Male and female child actors belong to a profession with wide public exposure and there is a potential danger of invading classes and roles not matching the developmental stage of the child. In this study, we would like to discuss international and domestic laws and future complementary measures surrounding legal and institutional issues that need to be considered for child actors. Although the basic rights for child workers are stated in the Constitution Article 32 Paragraph 5 and Labor Standards Act Articles 64 through 70, they are insufficient. Following the revised broadcasting deliberation regulations by the Korea Communication Commission and amendment of the Juvenile Protection Law, several changes are taking place in the working environment. In certain foreign places such as California, United States, the economic and educational rights of male and female child actors are being protected. Although legal and institutional frameworks for the male and female child actors are being reinforced, more consistent devices are needed. Consideration for working hours, regulations to keep up with learning while working, and preparation for physical and emotional influences are required to keep up with international changes.

：Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfu-sion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD.

Background: Bisphenol A (BPA) has been shown to affect brain and behavior in rodents and nonhuman primates, but there are few studies focusing on its relationship to human neurobehavior. We aimed to investigate the relationship between environmental exposure to BPA and childhood neurobehavior. Methods: Urinary BPA concentrations and behavioral and learning characteristics were assessed in a general population of 1,089 children, aged 8–11 years. The mainoutcomemeasuresweretheChildBehaviorChecklist(CBCL)andtheLearningDisabilityEvaluationScale(LDES). Results: Urinary levels of BPA were positively associated with the CBCL total problems score and negatively associated with the learning quotient from the LDES. The linear association with the CBCL anxiety/depression score and the quadratic association with the LDES listening score were significant after correction for multiple comparisons. Conclusions: Environmental exposure to BPA might be associated with childhood behavioral and learning development.Theresultssuggestpossiblenonmonotonicrelationships.Keywords: BisphenolA,childbehavior,childlearning, nonmonotonic dose–response. Bisphenol A (BPA) is a widespread industrial chemical. It is commonly used to synthesize polycarbonate plastics and epoxy resins, and these plastic polymers are extensively applied to the manufacture of various articles of daily use, including, for example, plastic food storage containers, polycarbonate beverage bottles, epoxy-lined food cans, baby formula bottles, and dental sealants, to name a few (Lakind & Naiman, 2011; Roy, Chakraborty & Chakraborty, 2009); thus increasing concerns have been raised over the past decade about the impact of environmental BPA on human health. Based on the chemical nature of BPA, an estrogenic compound, concerns have been directed largely

Objective The majority of studies on the associations between breastfeeding and cognitive functioning have focused on IQ, with only a few investigating learning skills, and none of the latter adjusting for maternal IQ. We examined the association between breastfeeding and learning abilities in school-aged children using a cross-sectional design. Methods We recruited 868 children, aged 8–11 years and parents completed the Learning Disability Evaluation Scale (LDES). Multivariable linear regression models were used and age, gender, area of residence, annual family income, maternal education, and maternal age at delivery, were included as covariates. Maternal IQ was added to further adjust for the effects of maternal cognitive ability. Path analysis was conducted to investigate the mediation effect of maternal IQ between breastfeeding and learning skills. Results Children who were ever-breastfed had higher learning quotient scores on the LDES (p = 0.001) as well as higher scores on subscales related to speaking (p = 0.001), reading (p = 0.005), writing (p = 0.004), spelling (p = 0.003), and mathematical calculation (p = 0.003) than the never-breastfed participants. All of these variables remained significant after adjusting for gestational and socioeconomic factors and for maternal IQ as covariates. The path analysis showed that breastfeeding had both indirect and direct effects on the learning quotient. Conclusions The results suggest that breastfeeding is positively associated with learning skills in school-aged children.

In recent years, detecting interactions between different genes has become a hot topic, for better understanding multigenic, complex diseases. For population-based genome-wide association studies (GWAS), a number of methods to detect gene-gene interactions such as logistic regression, multifactor dimensionality reduction (MDR) and support vector machine (SVM), have been applied. Bayesian approaches such as BEAM (Bayesian marker partition model) and DASSO-MB (detection of association using Markov Blanket) have also been suggested. However, the studies for family-based GWAS have been limited. In this study, we developed a new Markov Blanket-based algorithm called MB-TDT to find gene-gene interactions for pedigree data. A transmission disequilibrium test statistic was used as an association measure and the incremental association a Markov Blanket (IAMB) algorithm was applied to find Markov Blanket. This proposed MB-TDT method can identify a minimal set of causal SNPs, associated with a specific disease, thus avoiding an exhaustive search. By conducting a simulation study to compare MB-TDT with current methods, we show its superior high power in many cases, and lower false positive rates, in others.

The current cut-off score of the Korean version of the Childhood Autism Rating Scale (K-CARS) does not seem to be sensitive enough to precisely diagnose high-functioning autism. The aim of this study was to identify the optimal cut-off score of K-CARS for diagnosing high-functioning individuals with autism spectrum disorders (ASD).A total of 329 participants were assessed by the Korean versions of the Autism Diagnostic Interview - Revised (K-ADI-R), Autism Diagnostic Observation Schedule (K-ADOS), and K-CARS. IQ and Social Maturity Scale scores were also obtained.The true positive and false negative rates of K-CARS were 77.2% and 22.8%, respectively. Verbal IQ (VIQ) and Social Quotient (SQ) were significant predictors of misclassification. The false negative rate increased to 36.0% from 19.8% when VIQ was69.5, and the rate increased to 44.1% for participants with VIQ 69.5 and SQ 75.5. In addition, if SQ was83.5, the false negative rate increased to 46.7%, even if the participant's VIQ was ≤69.5. Optimal cut-off scores were 28.5 (for VIQ ≤ 69.5 and SQ ≤ 75.5), 24.25 (for VIQ 69.5 and SQ 75.5), and 24.5 (for SQ 83.5), respectively.The likelihood of a false negative error increases when K-CARS is used to diagnose high-functioning autism and Asperger's syndrome. For subjects with ASD and substantial verbal ability, the cut-off score for K-CARS should be re-adjusted and/or supplementary diagnostic tools might be needed to enhance diagnostic accuracy for ASD.

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 (Cronbach's 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.

Background Insufficient sunlight exposure, high junk food consumption, and sleep deprivation are known risk factors for decreased mental wellbeing, including elevated depressive symptoms and higher suicidality. The aforementioned risk factors for poor mental health are common among Korean adolescents. This study examined the effects of a school-based healthy-habits promotion intervention on depressive symptoms in Korean middle school students. Methods and Findings This intervention study with a pre-test/post-test design included 617 middle school students aged 13 to 15 in Seongnam, South Korea from April 2013 to November 2013. The 8-month educational intervention consisted of 3 slogans: 1) Sunlight exposure > 30 minutes a day, 2) No junk food, and 3) Healthy sleep. The primary outcome was depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Secondary outcomes included the number of days with sunlight exposure > 30 min/day, junk food consumption in a week, the frequency of staying up late, and problems with sleepiness. After controlling for confounders, the intervention was associated with a significant increase in the number of days of sunlight exposure of > 30 min/day (OR: 4.35, 95% CI: 3.20, 5.91) compared to before intervention. The intervention was associated with reduced odds of elevated depressive symptoms by 35% (OR: 0.65, 95% CI: 0.49, 0.85) compared to before intervention after adjustment for confounders. Conclusions These results suggest that school-based educational and behavioral intervention focused on healthy habits may decrease depressive symptoms in adolescents. Findings from our study could have significant clinical and public health implications in reducing depressive symptoms among adolescents through behavior and lifestyle changes.

The objective of this study was to evaluate the relationship between Attention deficit hyperactive symptoms and temperament and character profiles among preschool-age children. Total 694 preschool age children (mean age=5.7±0.45) were recruited for the study. The preschool Temperament and Character Inventory (psTCI) and DuPaul ADHD rating scale (K-ARS) were applied to evaluate the children. Statistical analysis was done to explore the association between psTCI profiles and ADHD symptom domains. The total ARS score was positively correlated with novelty seeking and harm avoidance. Inattention symptom domain was positively correlated both with novelty seeking and harm avoidance, whereas hyperactive symptom domain was only correlated with novelty seeking. Novelty seeking might be a universal genetic background for ADHD, and the level of harm avoidance could potentially be used to classify subtypes of ADHD.

Objectives:The objective of this study was to examine the perinatal and developmental risk factors of attention-deficit hyper - activity disorder (ADHD) diagnosed with a structured interview among Korean children. Methods:The current study included 924 children (6-15 years) recruited from schools in five Korean cities or a child psychia - try outpatient clinic of Seoul National University Children's Hospital. The parents of the children completed the structured diag- nostic interview for attention-deficit hyperactivity disorder, as well as questionnaires on perinatal and developmental risk factors. Results:Preterm delivery, severe maternal stress during pregnancy, change in primary care taker during the first three years, postpartum depression, and delayed first sentence showed a significant association with ADHD diagnosis. Conclusion:These findings suggest that perinatal and developmental factors contribute to development of ADHD in Korean children. Conduct of future research using a prospective design is needed in order to identify the causal relationship between ob- served risk factors and development of ADHD.

Objectives : The aim of this study is to investigate the effectiveness of treatment with osmotic-release oral system methylphenidate (OROS-MPH) on quality of life (QOL) in children with attention-deficit hyperactivity disorder (ADHD). Another aim is to assess the relationship between change in QOL and other factors including children`s symptoms and academic performance or parents` depression and parenting stress. Methods : A total of 111 medication-naive children with ADHD in a multicenter, open-label, 12-week trial of OROS-MPH completed an evaluation using diverse rating scales at two time points; at baseline and after 12 weeks of treatment. Scales for investigation of children included the Parent Report Form-Children`s Health and Illness Profile-Children`s Edition (PRF-CHIP-CE) on QOL, the ADHD Rating Scale-IV on symptoms, and the Academic Performance Rating Scale (APRS). The Beck Depression Inventory and Parenting Stress Index were used for assessment of their parents. Results : Total scores for mean PRF-CHIP-CE increased from at baseline to after 12 weeks of treatment (p

To evaluate the psychosocial distress of part-time occlusion therapy in intermittent exotropia. A total of 25 children (15 males and 10 females, aged 3 to 7 years, mean age 4.7 years) with intermittent exotropia were enrolled. Behavioral and psychosocial problems were assessed by the Korean Child Behavior Checklist (K-CBCL), which consists of eight categories of withdrawal, somatic problems, depression/anxiety, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior, and the Amblyopia Treatment Index (ATI). The ATI was designed to evaluate the three factors of compliance, adverse effect, and social stigma. The Parenting Stress Index (PSI) is a parent self-report designed to identify potentially dysfunctional parent–child systems. The K-CBCL was obtained before and after occlusion therapy, and the ATI and PSI were taken from parents only after occlusion therapy. We evaluated the change on the K-CBCL and the correlation between the K-CBCL and ATI. The attention problem assessed by the K-CBCL significantly decreased after occlusion therapy. On the ATI, the social stigma was relatively lower than compliance and adverse effect factors (Likert scale 2.64, 3.11, and 3.11, respectively). The somatic problem assessed by the K-CBCL and compliance on the ATI were significantly correlated (p = 0.014). There was no significant change in percentile scores of each subscale (parental dominant scale and child dominant scale) of the PSI. Total stress index before and after occlusion therapy was 97.16 ± 8.38 and 97.00 ± 8.16 respectively (p = 0.382). Occlusion therapy may influence the psychosocial impact on intermittent exotropia patients. Part-time occlusion significantly decreased the attention problem in children with intermittent strabismus. Children with a high somatic problem score on the KCBCL showed poor compliance to the part-time occlusion.

The objective of this study was to examine (a) anxiety and depression symptoms in children with Asperger syndrome (AS) compared to children with attention-deficit/hyperactivity disorder (ADHD) and children with depressive disorder; (b) parental anxiety and depressive symptoms in the three groups; and (c) the association between the anxiety and depression symptoms of children and their parents. The emotional and behavioral problems of 56 children with AS (48 boys, 8 girls, mean age, 9.39 ± 2.01 years) were compared with 56 ADHD children and 56 depressive disorder children, matched for age and sex. Their parents’ anxiety and depression symptoms were also compared. Trait-anxiety and internalizing problems in AS children were higher than those in ADHD children and as high as those in depressive disorder children (F = 8.83, p

This study examined the nature of cognitive and behavioral sex differences in children with autism spectrum disorders (ASDs) and two comparison groups: a group of typically developing (TD) children and a group of unaffected siblings of ASD children. Sex differences in core autistic symptoms, co-occurring behavioral symptoms, and cognitive styles were assessed in each group. Females with ASD were less severely affected than IQ- and age-matched males with ASD in the communication and repetitive stereotyped behavior domains, as measured by the ADI-R, but such sex differences were less significant than they were in the unaffected sibling group. Several behavioral/emotional symptom scores were significantly higher in male siblings than in female siblings. However, the ASD and TD groups did not show sex differences in any behavioral/emotional symptom scores. Males were superior in systemizing relative to empathizing, while the opposite was true for females in the unaffected sibling group and the TD children group; however, both males and females were superior in systemizing relative to empathizing in the ASD group. Our findings support the extreme male brain theory of autism, and further studies are needed to understand the mechanisms behind and developmental perspectives on the nature of sex differences in ASD.

N-Methyl-d-aspartate (NMDA) receptor, one of the glutamate receptors, has a role in the regulation of synaptic activity. It functions as an ion channel in the central nervous system and its inappropriate activation has been implicated in several neurological conditions. To test the association between candidate genes related with NMDA receptors and autism spectrum disorders (ASDs), we examined single nucleotide polymorphisms (SNPs) for GRIN2A and GRIN2B by using the family-based association test (FBAT) in 151 Korean trios. There was a statistically significant associations between ASDs and haplotypes in GRIN2B (bi-allelic mode additive model P-value=0.003; FDR P-value=0.012). This study supports a possible role of GRIN2B as a candidate gene for the etiology of ASDs.

：A significant proportion of children with autism spectrum disorders (ASD) have regression characterized by loss of previously acquired skills. The purpose of this study was to compare demographic, clinical characteristics and autism-related symptomatology of the children who have regression with children who don’t have regression.

：Memory (N=47) was the most prevalent savant skill in the savant ASD group (N=60). The savant ASD group had a statistically higher mean age and IQ score than did the nonsavant ASD group. Despite their high IQ profile, the savant ASD group showed a higher restricted, repetitive and stereotype behavior score on the K-ADI-R and higher language and cognitive scores on the K-ASDS than did the nonsavant ASD group.

：This study was conducted to develop a Korean algorithm of pharmacological and non-pharmacological treat-ment strategies in attention-deficit hyperactivity disorder (ADHD) and its specific comorbid disorders (e.g. tic disorder, depres-sive disorder, anxiety disorder, bipolar disorder, and oppositional defiant disorder/conduct disorder).

To assess sleep characteristics in children with ADHD through polysomnographic recordings and parental reports of sleep problems.Standard overnight polysomnography evaluation was performed to record sleep in 27 children with ADHD and 26 healthy controls, aged 7 to 12 years. The diagnosis of ADHD was determined by the Korean version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL-K). Children taking any medications or in poor health were excluded. All the subjects were assessed with the Children's Sleep Habits Questionnaire which was completed by parents. Overall neurobehavioral functioning was examined using various questionnaires, including the Child Behavioral Checklist (CBCL).Based on the findings from the questionnaire, the ADHD group had significantly higher scores on the sleep onset delay (p = 0.027), sleep duration (p = 0.032), night waking (p = 0.006), parasomnias (p = 0.016), daytime sleepiness (p = 0.007), and total sleep disturbance factors (p0.001) than children in the control group. However, there were no differences between ADHD and healthy groups on any polysomnographic variables, including sleep structure, arousals, and respiratory disturbances. Reported sleep problems were significantly associated with almost all subscales of CBCL as well as CBCL total score.The majority of sleep problems reported by the parents of ADHD children were not verified through the use of polysomnography. These findings raise the possibility that some of the reported sleep problems in ADHD may be related to disturbing behaviors which often characterize children with ADHD.

Objectives:The purpose of this study was to evaluate the prenatal, perinatal, and infancy history of children with autism spectrum disorder (ASD) as compared to unaffected siblings (SIB) and typically developing children (TC). Methods:Subjects with ASD, their SIB, and TC were recruited. All subjects were assessed using both the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R) and the Korean version of Autism Diagnostic Observation Schedule (K-ADOS) and were subsequently identified as affected or unaffected. Prenatal, perinatal, and infancy history was obtained from the primary caregivers and each facet was compared in those with ASD, the SIB, and the TC groups using SPSS ver. 17.0 (p

Background: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the patho physiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the α-2A-adrenergic receptor gene ( ADRA2A ) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A Msp I polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD. Methods: We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age- and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) single-photon emission com puted tomography. We performed image analyses with voxel-wise t statistics using SPM2. Results: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls ( p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele ( n = 13) at the ADRA2A Msp I polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele ( n = 8) ( p < 0.0005, uncorrected for multiple comparisons). Limitations: This study was limited by the small sample size, and we did not obtain gen etic data from the controls. Conclusion: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A Msp I polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

Background: The present study assessed the association between blood lead and urinary cotinine levels and inattentive and hyperactive symptoms and neurocognitive performance in children. Methods: A total of 667 children (age range 8–11) were recruited from nine schools in five Korean cities. The teachers and parents completed the Korean version of the Attention-deficit/hyperactivity disorder Rating Scales (K-ARS), and the children performed neurocognitive tests. Blood lead and urinary cotinine levels were then measured. Results: The inattentive, hyperactive, and total scores of the teacher-rated K-ARS were positively associated with blood lead level, and the results of the continuous performance test (CPT), Stroop Color–Word Test, and Children’s Color Trails Test were inversely associated with urinary cotinine level when controlled for age, gender, father’s educational level, maternal IQ, child’s IQ, residential area, birth weight, and cotinine (for lead) or lead (for cotinine). The association between blood lead level and commission errors score on the CPT disappeared when the effect of urinary cotinine level was controlled. Conclusions: These findings indicate that environmental exposure to tobacco smoke in children is associated with poor neurocognitive performance, and low levels of lead are associated with inattention and hyperactivity symptoms.

Objectives : The aim of this study was to investigate the effect of the clinical and demographic variables such as body weight, dosage, family history of attention-deficit hyperactivity disorder (ADHD), and psychiatric co-morbidity on the side-effects of OROS-Methylphenidate (OROS-MPH), and to evaluate the relationship between drug response and side effect severity. Methods : A total of 144 children (ages 6-18) with diagnosed ADHD were treated with OROS-MPH. Children were examined at baseline and after 1, 3, 6, 9, and 12 weeks of each treatment condition. The stimulant drug side effect rating scale (SERS), pulse rate, systolic blood pressure, diastolic blood pressure, and electrocardiogram (ECG) were evaluated to assess side effect profiles. Changes in these parameters from baseline were examined and analyzed. Results : Anorexia (30.95%) and insomnia (13.10%) were the most commonly reported side effects during this study. Insomnia and loss of appetite score increased at one week follow-up, but was sustained or decreased as treatment progressed. Small but significant increases in pulse rate and diastolic blood pressure were observed during treatment ; however, no clinically meaningful changes in ECG parameters were noted during the study. Low body weight, high dosage of OROS-MPH, and family history of ADHD were associated with cardiovascular side effect. In contrast, there was no significant relationship between OROS-MPH treatment response and the severity of side effect and no difference resulted between the responder and non-responder groups with respect to OROS-MPH dosage in the 12 weeks of follow-up. Conclusion : To the best of our knowledge, this study is the first Korean study to investigate comprehensive side effect profiles and their correlates in OROS-MPH treatment for ADHD children. OROS-MPH was well tolerated with no clinically significant side effects during the treatment period. In conclusion, low body weight, high dosage of OROSMPH, and family history of ADHD could be used as predictive factors in increasing pulse rate and blood pressure.

Although autism spectrum disorder (ASD) has been thought to have a substantial genetic background, major contributing genes have yet to be identified or success-fully replicated. Immunological dysfunction has been suggested to be associated with ASD, and T cell-medi-ated immunity was considered important for the devel-opment of ASD. In this study, we analyzed 163 ASD subjects and 97 normal controls by genomic quantitative PCR to evaluate the association between the copy num-ber variation of the 7q34 locus, harboring the TCRB gene, and ASDs. As a result, there was no significant difference of the frequency distribution of TCRB copy numbers between ASD cases and normal controls. TCRB gene copy numbers ranged from 0 to 5 copies, and the frequency distribution of each copy number was similar between the two groups. The proportion of the individuals with ＜2 copies of TCRB was 52.8% (86/163) in ASD cases and 57.1% (52/91) in the control group (p=0.44). The proportion of individuals with ＞2 copies of TCRB was 11.7% (19/163) in ASD cases and 12.1% (11/91) in the control group (p=0.68). After the ef-fects of sex were adjusted by logistic regression, ORs for individuals with ＜2 copies or ＞2 copies showed no significant difference compared with the diploid copy number as reference (n=2). Although we could not see the positive association, our results will be valuable in-formation for mining ASD-associated genes and for ex-ploring the role of T cell immunity further in the patho-genesis of ASD.Keywords: autism, copy number variation, T cell re-ceptor beta (TCRB), 7q34

Purpose This study aimed to examine the development of socializing and emotional expressions through vocalizations and joint attention (JA) behaviors in Korean-speaking children with autism spectrum disorder (ASD), compared to those with developmental delay (DD). Materials and methods Video samples were collected from 28 toddlers with ASD and 18 age-matched toddlers with DD, and vocalizations were each coded in detail for the purpose of this retrospective research. In addition to some statistical analysis, Computerized Language Analysis was conducted to obtain the final results. Results Although they produced a higher number of vocalizations than the DD group, the ASD group did not engage in emotional or social interactions with their caretakers, whereas the DD group did. The children with ASD used more atypical vocalizations and socially unengaged vocalizations than the children with DD did. JA using vocalizations in the ASD group, in particular, was largely dyadic, with triadic types occurring at a significantly lower frequency than those in the DD group. Conclusion Results from this study indicate the importance of assessing early vocalizations in toddlers with ASD, suggesting that some common symptoms of ASD, such as lack of typical, emotional, and social functions in early vocalizations, could be used to develop screening and intervention programs related to ASD.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component and environmental risk factors. Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), may play a role in the development of ASD. We genotyped nine single nucleotide polymorphisms (SNPs) in the NOS-I gene and nine SNPs in the NOS-IIA gene and carried out the transmission disequilibrium test (TDT) and haplotype analysis in 151 Korean ASD trios. We found preferential transmission of the A allele of rs8068149 (P = 0.039) and G allele of rs1060826 (P = 0.035) of NOS-IIA in ASD and the haplotype analysis revealed that the two haplotypes had significant associations (P = 0.014 and 0.031, respectively). The behavioral subdomain score of failure to use nonverbal behaviors to regulate social interaction in Autism Diagnostic Interview-Revised (ADI-R) was significantly higher in subjects with the GG or AG allele in rs1060826 of NOS-IIA compared to those who had the AA allele (P = 0.027). These results provide significant but weak evidence for an association between NOS-IIA and ASD in the Korean population. © 2008 Wiley-Liss, Inc.

Monoamine oxidase A gene (MAOA) has been thought to be a candidate gene implicated in autism spectrum disorder (ASD). This study evaluates the relationship between ASDs and MAOA markers (i.e., uVNTR and four single nucleotide polymorphisms (SNPs)) in 151 Korean family trios with children diagnosed with ASDs, and 193 unrelated Korean controls. The result of case-control global haplotype analysis also showed a statistically significant difference in haplotype frequencies between ASD patients and controls (male d.f.=5, p

Summary Objective Tonsillectomy is one of the most commonly performed procedures in children. However, parents often hesitate to agree to the procedure because of concerns of the possible harmful impact on their child's psychological health. The present study was performed to examine the short-term psychological impact on children who had undergone tonsillectomy. Methods Forty-three pediatric patients aged 3–11 years who underwent tonsillectomy were enrolled in the study. Postoperative pain was assessed using a 10-point visual analog scale (VAS) on postoperative days 1, 2, 7, and 21. The Korean version of the Child Behavior Checklist (K-CBCL) was given to the parents of the children to evaluate the psychosocial effect of tonsillectomy on the preoperative day and on postoperative day 21. Results There were no significant differences in postoperative pain according to age, tonsil size, degree of adhesion, or operation time. There was no significant relationship between postoperative pain score and K-CBCL score. Sociality, total behavioral problems, externalizing problems, internalizing problems, anxiety/depression, social immaturity, and emotional lability domain scores on the K-CBCL were improved significantly. Conclusions Improvements in general emotional and social status were observed at 3 weeks after tonsillectomy. Tonsillectomy itself does not have a harmful effect on children's psychological status.

Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in neuroplasticity and the neuropathology of the central nervous system. This study evaluated the relationship between autism spectrum disorders (ASDs) and polymorphisms of PTGS2 (the gene encoding Cox-2) with 151 Korean family trios including children with ASDs. We found that the A allele of rs2745557 was preferentially transmitted in ASDs (p < 0.01) and that the GAAA haplotype was significantly associated with ASDs (p < 0.01). We also observed statistically significant associations between each genotype and the specific symptom domain scores of ADOS and ADI-R, including communication, qualitative abnormalities in reciprocal social interaction, and overactivity/agitation.

The potential role of the serotoninergic system in the development of autistic disorder has long been suggested based on the observation of hyperserotoninemia in autistic subjects and the results of drug treatment studies. Promoter region polymorphisms (5-HTTLPR) of the serotonin transporter gene (SLC6A4) and the 5-HT2A receptor gene (HTR2A) have been studied as potential candidate genes in autism spectrum disorder (ASD). The objective of this family-based linkage/association study is to evaluate the relationship between ASD and 5-HTTLPR as well as that between some SNPs of HTR2A and ASD in Korean trios by using the transmission disequilibrium test (TDT). Genotyping was performed for 5-HTTLPR and two single nucleotide polymorphisms (SNPs) (-1438G/A and 102T/C) of HTR2A. The TDT, linkage disequilibrium (LD) analysis and haplotype analysis were performed. This study comprised 126 complete trios of ASD patients and both parents. With regard to the transmission of 5-HTTLPR, the long allelic variant was preferentially transmitted in the ASD subjects. Based on the TDT results, there was no significant difference in the transmission of the two SNPs of HTR2A. However, in the results of the haplotype analysis, the AT haplotype demonstrated significant evidence of association with autism. The global χ2 test for haplotype transmission revealed a significant association between HTR2A and autism. Although we identified a significant association between ASD and 5-HTTLPR as well as between ASD and HTR2A, it cannot exclude the chance finding because of the low level of statistical significance and relatively small power. We believe that further studies are required to examine the relationship between serotonin-related genes and the behavioral phenotypes of ASD in the Korean population.

In addition to its classical role as a regulator of telomere length, recent reports suggest that telomerase reverse transcriptase (TERT) plays a role in the transcriptional regulation of gene expression such as β-catenin-responsive pathways. Silencing or over-expression of TERT in cultured NPCs demonstrated that TERT induced glutamatergic neuronal differentiation. During embryonic brain development, expression of transcription factors involved in glutamatergic neuronal differentiation was increased in mice over-expressing TERT (TERT-tg mice). We observed increased expression of NMDA receptor subunits and phosphorylation of α-CaMKII in TERT-tg mice. TERT-tg mice showed autism spectrum disorder (ASD)-like behavioral phenotypes as well as lowered threshold against electrically induced seizure. Interestingly, the NMDA receptor antagonist memantine restored behavioral abnormalities in TERT-tg mice. Consistent with the alteration in excitatory/inhibitory (E/I) ratio, TERT-tg mice showed autism-like behaviors, abnormal synaptic organization, and function in mPFC suggesting the role of altered TERT activity in the manifestation of ASD, which is further supported by the significant association of certain SNPs in Korean ASD patients.

Background/Aims: Autism spectrum disorders (ASD) are complex neuropsychiatric disorders having a genetic risk factor. The association and linkage study for the γ-aminobutyric acid type A receptor β3 subunit gene (GABRB3), located within the chromosome 15q11-q13 autism candidate region, and ASD have been evaluated. The aim of this study was to investigate the association between GABRB3 and ASD in the Korean population. Methods: The present study was conducted with the detection of four single-nucleotide polymorphisms (rs1426217, rs2081648, rs890317, rs981778) in GABRB3 and association analysis in 104 Korean ASD trios using the transmission disequilibrium test. Results: The transmission disequilibrium test demonstrated that an allele at rs2081648 showed preferential transmission (p = 0.027). One haplotype, including all examined markers in GABRB3, demonstrated significant association (p = 0.043), but the global χ2 test for haplotype transmission did not reveal an association between GABRB3 and ASD (χ2 = 15.516, d.f. = 15). Conclusion: Our finding suggested that single-nucleotide polymorphisms in GABRB3 may play a significant role in the genetic predisposition to ASD in the Korean population.

Background: The objective of this study was to evaluate the relationship between symptoms of attention deficit hyperactivity disorder (ADHD) and biogenetic temperament, as assessed by the Junior Temperament and Character Inventory (JTCI) in Korean elementary school children. Sampling and Methods: Five hundred and sixteen elementary school students (254 boys and 262 girls; age range 9–14 years, mean age 11.0 ± 1.0 years) were studied. The Junior Temperament and Character Inventory, both the self-rating and parent rating scales, the DuPaul ADHD rating scale (ARS-IV) for parents and teachers and the Child Behavior Checklist have been completed by study subjects. Children with high ARS-IV scores (the upper 10th percentile, n = 52) were defined to have ADHD. Fifty-two age- and sex-matched non-ADHD control subjects were selected randomly from a pool of 464 subjects. Results: Inattention and hyperactivity/impulsivity symptoms correlated positively with Novelty Seeking in both children and parent ratings. These symptoms correlated negatively with Persistence, Self-Directedness and Cooperativeness. Novelty Seeking also had significant correlations with attention problems, delinquent behavior, aggressive behavior, externalizing problems and social problems in the Child Behavior Checklist. The ADHD group (n = 52) had higher scores of Novelty Seeking and lower scores of Self-Directedness and Cooperativeness, compared with the control group. Conclusions: There were significant correlations between ADHD symptoms and Novelty Seeking. Current findings suggest that Novelty Seeking and ADHD share biogenetic backgrounds.

The objective of this study was to evaluate the relationship between attention deficit-hyperactivity/impulsivity symptoms and Internet addiction. In total, 535 elementary school students (264 boys, 271 girls; mean age, 11.0 +/- 1.0 years) were recruited. The presence or severity of Internet addiction was assessed by the Young's Internet Addiction test. Parents and teachers of the children completed the DuPaul's attention deficit hyperactivity disorder (ADHD) rating scale (ARS; Korean version, K-ARS) and Child Behavior Checklists. Children with the highest and lowest quartiles in K-ARS scores were defined to be in ADHD and non-ADHD groups, respectively. Five children (0.9%) met criteria for a definite Internet addiction and 75 children (14.0%) met criteria for a probable Internet addiction. K-ARS scores had significant positive correlations with Young's Internet Addiction test scores. The Internet addiction group had higher total scores of K-ARS and ADHD-related subcategories in the Child Behavior Checklists than the non-addiction group. The ADHD group had higher Internet addiction scores compared with the non-ADHD group. Therefore, significant associations have been found between the level of ADHD symptoms and the severity of Internet addiction in children. In addition, current findings suggest that the presence of ADHD symptoms, both in inattention and hyperactivity-impulsivity domains, may be one of the important risk factors for Internet addiction.

ObjectivesThe objective of this family-based whole exome sequencing (WES) is to examine genetic variants of autism spectrum disorder (ASD) in Korean population.MethodsThe probands with ASD and their biological parents were recruited in this study. We ascertained diagnosis based on DSM-5™ criteria, using Autism Diagnostic Observation Schedule and Autism Diagnostic Interview–Revised. We selected probands with typical phenotypes of ASD both in social interaction/communication and repetitive behaviour/limited interest domains, with intellectual disability (IQ < 70), for attaining homogeneity of the phenotypes. First, we performed WES minimum 50× for 13 probands and high-coverage pooled sequencing for their parents. We performed additional WES for 38 trio families, at least 100× depth. De novo mutations were confirmed by Sanger sequencing. All the sequence reads were mapped onto the human reference genome (hg19 without Y chromosome). Bioinformatics analyses were performed by BWA-MEM, Picard, GATK, and snpEff for variant annotation. We selected de novo mutation candidates from probands, which are neither detected in two pooled samples nor both parents.ResultsFifty-one subjects with ASD (5 females, 40∼175 months, mean IQ 42) and their families were included in this study. We discovered 109 de novo variants from 46 families. Twenty-nine variants are expected to be amino acid changing, potentially causing deleterious effects. We assume CELSR3, MYH1, ATXN1, IDUA, NFKB1, and C4A/C4B may have adverse effect on central nerve system.ConclusionsWe observed novel de novo variants which are assumed to contribute to development of ASD with typical phenotypes and low intelligence in WES study.Disclosure of interestThis work has been supported by Healthcare Technology R&D project (No: A120029) by Ministry of Health and Welfare, Republic of Korea.

Detecting genetic interactions associated with complex disease is a major issue in genetic studies. Although a number of methods to detect gene-gene interactions for population-based Genome-Wide Association Studies (GWAS) have been developed, the statistical methods for family-based GWAS have been limited. In this study, we propose a new Bayesian approach called MB-TDT to find high-order genetic interactions for pedigree data. The MB-TDT method combines the Markov blanket algorithm with classical Transmission Disequilibrium Test (TDT) statistic. The Incremental Association Markov Blanket (IAMB) algorithm was adopted for large-scale Markov blanket discovery. We evaluated the proposed method using both real and simulated data sets. In a simulation study, we compared the power of MB-TDT with conditional logistic regression, Multifactor Dimensionality Reduction (MDR) and MDR-pedigree disequilibrium test (MDR-PDT). We demonstrated the superior power of MB-TDT in many cases. To demonstrate the approach, we analysed the Korean autism disorder GWAS data. The MB-TDT method can identify a minimal set of causal SNPs associated with a specific disease, thus avoiding an exhaustive search.