Reliability and Validity of the Korean Version of Disruptive Behavior Disorders Rating Scale, DSM-5 Version-Parent Form.

OBJECTIVE: Disruptive behavior disorder (DBD) adversely impacts children and adolescents. However, a comprehensive and cost-effective scale to assess DBD is lacking in Korea. Therefore, this study translated the Disruptive Behavior Disorders Rating Scale (DBDRS) into Korean and analyzed its psychometric properties. METHODS: Parents and primary caregivers of non-clinical (n=429) and clinical (n=28) children and adolescents aged 6-15 years were included in the analysis. Confirmatory factor analysis was conducted; further, concurrent validity and internal consistency were investigated using correlation analysis and Cronbach's alpha, respectively. Furthermore, discriminative capacity was estimated using receiver operating characteristic curve analysis. RESULTS: The four-factor model of K-DBDRS showed good model fit indices and factor loadings, which supported the construct validity of the scale. Strong correlations between K-DBDRS and related measurements were observed, and a robust level of Cronbach's alpha was confirmed (0.891-0.933). The discriminative capacity of the scale was good, based on the area under the curve values (0.933-0.953). CONCLUSION: This study indicated that the K-DBDRS is an appropriate screening tool for Korean children and adolescents. Thus, this scale can be applied in clinical and community settings to identify children and adolescents with disruptive behavior disorders.

Prospective Association Between Online Game Use and Risk of Internet Gaming Disorder in Korea: 12-Month Follow-up Results From the iCURE Study.

Children and adolescents' Internet game use has both functional and dysfunctional aspects. This study aimed to examine how changes in online gaming behaviors impact the risk of Internet gaming disorder (IGD). We observed 1318 adolescent online game users. Baseline and 12-month follow-up evaluations were performed, and it was defined whether the average online gaming time per day exceeded 1.5 hours and whether the number of gaming days per week exceeded 4 days. Gaming disorder was defined using the Internet Game Use-Elicited Symptom Screen. Multiple logistic regression was performed to examine the difference in the incidence rate ratio (IRR) of IGD risk according to changes in gaming time or frequency. Results indicated the IRR of IGD risk was 2.54 for the increased time spent group and 2.38 for the consistent higher time spent group against the consistent lower time spent group. The IRR was 3.76 for the increased frequency group and 2.92 for the consistent higher frequency group against the consistent lower frequency group. Therefore, managing Internet game use not to exceed 1.5 hours per day on average and 4 days per week would help prevent elevation of IGD risk.

Diagnostic Usefulness of an Ultra-Brief Screener to Identify Risk of Online Gaming Disorder for Children and Adolescents.

OBJECTIVE: This study examined the diagnostic validity of a three-item ultra-brief screening tool for online gaming disorder in line with the gaming disorder criteria in the International Classification of Diseases 11th Revision. METHODS: The Three-item Gaming disorder Test-Online-Centered (TIGTOC) was composed of three items using a four-point Likert scale selected from the Internet Game Use-Elicited Symptom Screen (IGUESS). Among a cohort of 2319 young-adolescent Internet users, the baseline data of 228 healthy controls and 45 Internet-gaming-disorder cases were analyzed. Receiver operation characteristic (ROC) analysis was performed using mental health specialists' diagnoses as the gold standard. RESULTS: The ROC curve analysis showed an area under the curve of 86%. Using a cut-off score of 4 from a full range of 0-9, the sensitivity, specificity, and Cronbach's α were 72%, 90%, and 0.811, respectively. TIGTOC scores was positively associated with time spent on online gaming, depressive symptoms, attention-deficit/hyperactivity disorder symptoms, and addictive Internet use. CONCLUSION: The TIGTOC appears to be a brief, valid, and reliable screening tool for online gaming disorder within the community or in primary care settings.

Low self-control and aggression exert serial mediation between inattention/hyperactivity problems and severity of internet gaming disorder features longitudinally among adolescents.

OBJECTIVES: We examined serial mediating roles of low self-control and aggression in explaining relationships between levels of inattention and hyperactivity problems (IHPs) and severity of Internet gaming disorder (IGD) features when exposed to online games among adolescents without Attention deficit hyperactivity disorder (ADHD) stratified by gender using three-wave longitudinal study. METHOD: The sample comprised a total of 1,732 family dyads from a study that was conducted among seventh graders without diagnoses of ADHD at baseline. Levels of IHPs were assessed by the parent reported Korean version of the ADHD rating scale at baseline (wave1). Severity of IGD features was assessed by the Internet Game Use-Elicited Symptom Screen (IGUESS) at wave3. Both levels of self-control (wave1) and aggression (wave2) were assessed by self-report. The mediating role of low self-control and aggression in the relationships between level of IHPs and severity of IGD were evaluated using serial mediation analysis separately for each gender. RESULTS: Levels of IHPs were related directly to severity of IGD features in both genders. The indirect effects via low self-control were also significant in both genders, however, the indirect effects via aggression was significant only in women. The serial mediation effect via low self-control and aggression between levels of IHPs and IGD features was significant in both genders (men, coefficient:0.009, 95%CI 0.005-0.019; women, coefficient:0.010, 95%CI:0.005-0.026). CONCLUSION: We revealed a possible mechanism underlying a serial mediation chain from low self-control to aggression explaining the effects of IHPs on severity of IGD features. However, this conclusion should be taken with a caution, because the effect sizes were very low.

A partial mediation effect of father-child attachment and self-esteem between parental marital conflict and subsequent features of internet gaming disorder in children: a 12-month follow-up study.

BACKGROUND: This study evaluated whether parent-child attachment and self-esteem may mediate the relationship between parental marital conflict and increases in features of internet gaming disorder (IGD) in children at 1 year. METHODS: The baseline and one-year follow-up data for 268 pre-teens aged between 9 and 10 from the Internet User Cohort for Unbiased Recognition of Gaming Disorder in Early Adolescence (iCURE) study were collected. The students were children at low risk for IGD in the initial self-reported assessment, anyone living with both parents, current game user at baseline, and those who completed a 12-month follow-up assessment. The Internet Game Use-Elicited Symptom Screen (IGUESS) was used to identify increases in IGD features at 12 months. To examine a potential mediation effect, structural equation modeling was performed. RESULTS: The direct effect was statistically significant, and parental marital conflict at baseline significantly predicted the increases in IGD features in children at the 12-month follow-up after adjusting for gender, sex, socioeconomic status, and baseline IGUESS score (ß = 0.206, P = 0.003). The indirect effect showed that attachment to fathers through self-esteem was a significant mediating effect (ß = 0.078, P = 0.045). Parental marital conflicts were associated with increases in IGD features in children through poor father-child attachment, and in turn, the lower levels of self-esteem in the children. CONCLUSIONS: Parents, especially fathers, should make an effort to bond with their children to reduce the risk of their children's developing the IGD features.

Relationship between the experience of online game genre and high risk of Internet gaming disorder in Korean adolescents.

OBJECTIVES: This study examined the association between high risk of Internet gaming disorder (IGD) and online game genres used by adolescents. METHODS: The data derived from the baseline data of the Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence. A total 1,532 middle school students who use online games included. The participants reported the names of the online games they used during the past year. Game genres were categorized into role playing games (RPGs), shooting, multiplayer online battle arena (MOBA), simulation, arcade, sports and action games. The risk of IGD was measured using the Internet Gaming Use-Elicited symptom Screen. The relationship between the experience of online game genre and high risk of IGD was analyzed using multiple logistic regression model. RESULTS: The game time of a student was longer if he or she had an experience of RPGs, shooting games, MOBA games, simulation games, and action games. The direct and independent association between high risk of IGD in adolescents and the genres of RPGs, simulation games and MOBA were found to be odds ratios 1.52 (95% confidence interval [CI], 1.03 to 2.26); 1.59 (95% CI, 1.03 to 2.45); and 1.51 (95% CI, 1.03 to 2.21), respectively after adjusted the potential confounding variables and the use of other online game genres. CONCLUSIONS: The present cross-sectional study has found an association between online game genres and the risk of IGD in adolescents attending a school. A cohort study should verify the causal association in future.

Gaming patterns and related symptoms in adolescents using cluster analysis: Baseline results from the Internet User Cohort for Unbiased Recognition of Gaming Disorder in Early Adolescence (iCURE) study.

PURPOSE: The risk and protective factors of Internet gaming disorder (IGD) could vary by individual. The identification of more homogeneous subgroups may lead to better understanding of gaming behaviors and their consequences in adolescents. The purpose of this study was to investigate the prevalence of IGD among the subgroups defined by cluster analysis in adolescents. METHODS: A total of 2319 adolescents were enrolled in the Internet User Cohort for Unbiased Recognition of Gaming Disorder in Early Adolescence (iCURE) study at baseline. Self-reported IGD was assessed with a DMS-5 adapted measurement. Smartphone addiction, musculoskeletal discomfort, and dry eye symptoms were evaluated by self-administered questionnaires. Cluster analysis was performed using risk and protective factors of IGD after considering multicollinearity. RESULTS: Three different clusters were identified. Cluster 1 (19.2%) was users with combined potential psychological and social issues. Cluster 2 (32.3%) was users with potential social but no psychological issues. Cluster 3 (45.6%) was users with no potential issues of either a social or psychological nature. Adolescents from both clusters 1 and 2 showed higher degrees of IGD, smartphone addiction, musculoskeletal discomfort, and dry eye symptoms than did those from cluster 3. Also compared with adolescents in cluster 3, those in cluster 1 showed statistically higher risks of IGD (aOR:11.9, 95%CI:7.5-19.9), smartphone addiction (aOR:5.4, 95%CI:4.0-7.2), musculoskeletal discomfort (aOR:2.6, 95%CI:2.1-7.4), and dry eye symptoms (aOR:3.8, 95%CI:3.0-4.9). Those in cluster 2 also showed statistically higher risk of IGD, smartphone addiction, musculoskeletal discomfort, and dry eye symptoms compared with cluster 3 (aOR:4.5, 95%CI:2.8-7.6; aOR:2.8, 95%CI:2.1-3.7; aOR:1.6, 95%CI:1.3-1.9; and aOR:1.9, 95%CI:1.6-2.4, respectively). CONCLUSIONS: Clustering based on the risk and preventive factors of IGD may be suitable for determination of high risk of IGD in adolescents. However, we need to confirm the usefulness and clinical application of the classifications by observing their longitudinal changes.

Reciprocal relationship between depression and Internet gaming disorder in children: A 12-month follow-up of the iCURE study using cross-lagged path analysis.

OBJECTIVES: Previous studies have reported an association between Internet gaming disorder (IGD) and depression, but the directionality of the relationship remains unclear. Therefore, we examined the reciprocal relationship between level of depressive symptoms and IGD among children in a longitudinal study. METHODS: Research panels for this study consisted of 366 elementary-school students in the iCURE study. All participants were current Internet users, so they could be considered an at-risk population for IGD. Self-reported severity of IGD features and level of depression were assessed by the Internet Game Use-Elicited Symptom Screen and Children's Depression Inventory, respectively. Follow-up assessment was completed after 12 months. We fitted cross-lagged structural equation models to investigate the association between the two variables at two time points contemporaneously. RESULTS: The cross-lagged analysis revealed that level of depression at baseline significantly predicted severity of IGD features at the 12-month follow-up (ß = 0.15, p = .003). Severity of IGD features at baseline also significantly predicted level of depression at the 12-month follow-up (ß = 0.11, p = .018), controlling for possible confounding factors. CONCLUSIONS: The cross-lagged path analysis indicates a reciprocal relationship between severity of IGD features and level of depressive symptoms. Understanding the reciprocal relationship between depressive symptoms and severity of IGD features can assist in interventions to prevent both conditions. These findings provide theoretical support for prevention and remediation plans for IGD and depressive symptoms among children.

The association between aggression and risk of Internet gaming disorder in Korean adolescents: the mediation effect of father-adolescent communication style.

OBJECTIVES: Open and supportive communication between parents and children is known to reduce adolescents' delinquent behavior. Recently, the risk of Internet gaming disorder (IGD) has been increasing in adolescents. The purpose of this study was to investigate the mediating effects of parent-child communication styles on the relationship between adolescent aggressiveness and risk of IGD. METHODS: Participants in this study were 402 first-year students from 4 middle schools in Seoul who enrolled in the Internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE) and completed baseline assessment in 2016. The structural equation model was constructed based on an aggression questionnaire, the Internet game use-elicited symptom screen, a mother-child communication inventory, and a father-child communication inventory. RESULTS: Adolescents' aggressiveness was found to be related to their risk of IGD. The father-child communication style mediated the relationship between aggression and risk of IGD. However, the mother-child communication style had no mediating effect. CONCLUSIONS: Our findings suggest that fathers should make an effort to improve open and positive communication skills with their children, because the father-child communication style plays an important role in the relationship between adolescent aggressiveness and risk of IGD.

Study protocol of the internet user Cohort for Unbiased Recognition of gaming disorder in Early adolescence (iCURE), Korea, 2015-2019.

INTRODUCTION: In 2013, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) proposed nine internet gaming disorder (IGD) diagnostic criteria as a condition warranting further empirical and clinical research. The aim of this study is to clarify the natural and clinical courses of IGD proposed DSM-5 in adolescents and to evaluate its risk and protective factors. METHODS AND ANALYSIS: The Internet user Cohort for Unbiased Recognition of gaming disorder in Early Adolescence (iCURE) study is an ongoing multidisciplinary, prospective, longitudinal cohort study conducted in 21 schools in Korea. Participant recruitment commenced in March 2015 with the goal of registering 3000 adolescents. The baseline assessment included surveys on emotional, social and environmental characteristics. A parent or guardian completed questionnaires and a structured psychiatric comorbidity diagnostic interview regarding their children. Adolescents with the Internet Game Use-Elicited Symptom Screen total scores of 6 or higher were asked to participate in the clinical diagnostic interview. Two subcohorts of adolescents were constructed: a representative subcohort and a clinical evaluation subcohort. The representative subcohort comprises a randomly selected 10% of the iCURE to investigate the clinical course of IGD based on clinical diagnosis and to estimate the false negative rate. The clinical evaluation subcohort comprised participants meeting three or more of the nine IGD criteria, determined by clinical diagnostic interview, to show the clinical course of IGD. Follow-up data will be collected annually for the 3 years following the baseline assessments. The primary endpoint is 2-year incidence, remission and recurrence rates of IGD. Cross-sectional and longitudinal associations between exposures and outcomes as well as mediation factors will be evaluated. ETHICS AND DISSEMINATION: This study is approved by the Institutional Review Board of the Catholic University of Korea. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (identifier: NCT02415322).

Antitumor activity of EGFR targeted pH-sensitive immunoliposomes encapsulating gemcitabine in A549 xenograft nude mice.

Immunoliposomes directed by monoclonal antibodies are promising vehicles for tumor targeted drug delivery. Development of a long-circulating formulation of pH-sensitive liposomes (PSLs) with epidermal growth factor receptor (EGFR) antibody attached was designed and tested using A549 cells and BALB/c-nu/nu mouse tumor model. PSL formulation was prepared using small unilamellar vesicles of DOPE and CHEMS (6:4 molar ratio) by REV method. The average size and zeta-potential of the formulation measured by dynamic laser-light scattering were approximately 146+/-43.9 nm (PDI=0.09+/-0.02) and -1.77+/-0.03 mV, respectively. A549 cells were xenotransplanted into BALB/c-nu/nu mice and various formulations of gemcitabine (gem), such as in its free form, PSLs or Ab-PSLs, were injected intravenously via a tail vein. The rate of tumor volume increment in Ab-PSLs with gem-treated group was remarkably slower than that of other drug-treated group. The tumor from Ab-PSLs with gem 160 mg/kg-injected group exhibited a markedly lowest account of PCNA labeled cells and had highest TUNEL-positive cells among tested. This suggests that treatment of Ab-PSLs with gem resulted in an increased apoptosis of tumor cells, leading to tumor growth inhibition. These results demonstrate that PSLs provide an efficient and targeted delivery of gemcitabine and may represent a useful new treatment approach for tumors which overexpress the EGFR.

Therapeutic efficacy of DNA-loaded PLGA microspheres in tumor-bearing mice.

In vivo gene therapy was attempted using poly-(D,L-lactic-co-glycolic acid) microspheres containing the interleukin-12 gene (p2CMVmlL12) in colon adenocarcinoma (CT-26)-bearing Balb/ c mice. Treatment with IL-12-loaded microspheres inhibited tumor growth significantly compared to a control group treated with free IL-12 DNA, though the degree of tumor inhibition was not dependent on the amount of IL-12 gene loaded. Combining gene therapy with 5-fluorouracil (50 mg/kg) treatment further inhibited tumor growth compared with gene therapy alone. The results indicate that microsphere formulations of pDNA may provide an efficient gene delivery system.