An exploratory study on spatiotemporal clustering of suicide in Korean adolescents.

BACKGROUND: Adolescent suicides are more likely to form clusters than those of other age groups. However, the definition of a cluster in the space-time dimension has not been established, neither are the factors contributing to it well known. Therefore, this study aimed to identify space-time clusters in adolescent suicides in Korea and to examine the differences between clustered and non-clustered cases using novel statistical methods. METHODS: From 2016 to 2020, the dates and locations, including specific addresses from which the latitude and longitude of all student suicides (aged 9-18 years) in Korea were obtained through student suicide reports. Sociodemographic characteristics of the adolescents who died by suicide were collected, and the individual characteristics of each student who died by suicide were reported by teachers using the Strengths and Difficulties Questionnaire (SDQ). Density-Based Spatial Clustering of Applications with Noise (DBSCAN) analysis was used to assess the clustering of suicides. RESULTS: We identified 23 clusters through the data analysis of 652 adolescent suicides using DBSCAN. By comparing the size of each cluster, we identified 63 (9.7%) spatiotemporally clustered suicides among adolescents, and the temporal range of these clusters was 7-59 days. The suicide cluster group had a lower economic status than the non-clustered group. There were no significant differences in other characteristics between the two groups. CONCLUSION: This study has defined the space-time cluster of suicides using a novel statistical method. Our findings suggest that when an adolescent suicide occurs, close monitoring and intervention for approximately 2 months are needed to prevent subsequent suicides. Future research using DBSCAN needs to involve a larger sample of adolescents from various countries to further corroborate these findings.

Association between Maternal Personality Traits and Children's Sleep Disturbance: A Population-based Cohort Study in Republic of Korea.

Objective: Sleep affects the development and severity of psychiatric symptoms in children, and maternal personality traits may influence children's sleep. We aimed to confirm the longitudinal effect of maternal personality traits on children's sleep disturbance using cohort data from the Panel Study on Korean Children. Methods: Maternal personality traits were assessed using the Personality Assessment Inventory in 2009, and the sleep disturbance of children was assessed using parent survey data from 2010 to 2014 (2nd-6th waves). Among the 11 clinical scales of the Personality Assessment Inventory, the 5 scales that showed the most significant correlations were analyzed. Presence or absence of child sleep disturbance was evaluated with a chi-square test, and the effect of the Personality Assessment Inventory was assessed by a binary logistic regression analysis with child sleep disturbance as the dependent variable. Results: Of the 171 mother-child dyads, 92 were classified into the sleep disturbance group and 79 were classified into the normal sleep group. Maternal somatic concerns showed a significant relationship with children's sleep disturbance at years 2 and 3. Maternal borderline features demonstrated a significant relationship with children's sleep disturbance from years 2 to 5. The binary logistic regression analysis revealed a significant association between high borderline features and children's sleep disturbance at years 2 and 3. Conclusion: High maternal borderline features evaluated at child age 1 were related to sleep disturbance in early childhood. In assessing a children's sleep problems, it may be important to examine mothers' dysfunctional personality traits.

Intelligence-Dependent Differential Effects of Media Exposure on Executive Function Changes in Children: A Population-Based Cohort Study With a Longitudinal Design.

BACKGROUND: Excessive media use is known to be associated with executive dysfunction in children, but it's unclear whether this exposure can lead to long-term changes of executive function. This study aimed to investigate the association between media exposure and longitudinal changes in executive function within a population-based study, while considering the potential influence of intelligence. METHODS: This study used data from 1,209 participants in the Panel Korea Study for Children. The children's media exposure was measured at ages 7 and 8, and executive function was evaluated annually from ages 7 to 10 using the Executive Function Difficulty Screening Questionnaire. Participants were grouped by media exposure level (low, medium, or high), and longitudinal changes in executive function were analyzed using linear mixed effects models. Subgroup analysis was conducted to investigate how executive function changes varied based on intelligence within each media exposure group. RESULTS: Children with high media exposure (n = 97) had severer executive function difficulties than those with low (n = 141) or medium (n = 971) exposure in all waves. The high exposure group demonstrated persistent higher executive function difficulties up to age 10 after controlling for child gender, intelligence, parental education level and maternal depression. Children with intelligence quotient (IQ) ≤ 100 in the medium to high media exposure group had significantly more severe executive function difficulties than those with IQ > 100. CONCLUSION: This study provided evidence of a longitudinal negative association between media exposure and executive function. The findings suggest that excessive media exposure may lead to long-term changes in executive function in children and highlight the importance of implementing targeted interventions and educational strategies to mitigate the potential negative effects of excessive media use, particularly for children with lower cognitive abilities.

The Core Symptoms of Adolescents Online and Offline Gambling in South Korea Using Network Analysis.

OBJECTIVE: Adolescent gambling is rapidly increasing recently. However, little is known about the core feature of adolescent gambling that should be the treatment target for adolescents. Thus, the objective of this study was to determine the core symptom of adolescent gambling using network analysis with large-scale data targeting community indwelling adolescents. METHODS: We used dataset of the 2018 national survey on youth gambling problems collected by the Korea Center on Gambling Problems to explore symptom networks of gambling in adolescents. Of 17,520 respondents in the dataset of the 2018 national survey on youth gambling problems collected by the Korea Center on Gambling Problems, 5,619 adolescents with experience of gambling were included in the analysis. We computed an association network, a graphical least absolute shrinkage and selection operator, and a directed acyclic graph to model symptom interactions. RESULTS: In each network of online, offline, and all gambling, stealing money or other valuable things in order to gamble or pay off gambling debts was the most centrally situated and skipping practice followed by dropping out of activities. Especially strong connections emerged between stealing money or other valuable things in order to gamble or pay off gambling debts and academic performance degradation due to gambling. Feeling bad due to gamble and skipping hanging out with friends who do not gamble emerged as a highly central node that might be distinctive to adolescents with online gambling. CONCLUSION: These findings demonstrate central features of adolescent gambling. Different associations among specific network nodes suggest the existence of distinctive psychopathological constructs between online and offline gambling.

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.

Association between Attention Deficit Hyperactivity Disorder Medication and Depression: A 10-year Follow-up Self-controlled Case Study.

Objective: There is clinical concern that the stimulant methylphenidate (MPH) might increase the risk of depression, particularly in children. This study aimed to investigate the association between MPH use and the risk of depression. Methods: A population-based electronic medical records database was used. We obtained claims data for prescription of ADHD medication, diagnosis of depression, and prescription of antidepressant medication between January 2007 and December 2016 for 43,259 individuals aged 6 to 19 who were diagnosed with ADHD between July 1, 2007 and December 31, 2007. The final analysis was based on 2,330 eligible participants. A self-controlled case series design was used to identify risk factors for major depressive disorder (MDD). Results: An elevated MDD risk was found during the 90 days before MPH exposure, with an incidence rate ratio (IRR) of 12.12 (95% confidence interval [95% CI]: 10.06-14.61, p < 0.0001). During methylphenidate treatment, the IRR was 18.06 with a 95% CI of 16.67 to 19.56 (p < 0.0001), but it returned to baseline levels after day 31 of MPH treatment discontinuation. The IRR for patients aged 6 to 9 years was 13.11 (95% CI: 9.58-17.95) during the 90 days before MPH exposure, and 17.7 (95% CI: 15.6-20.08) during MPH treatment, but returned to baseline levels after discontinuation of MPH treatment. Conclusion: We confirmed the temporal relationship between depression and methylphenidate use in young people with ADHD. Though the absolute risk is low, the risk of depression should be carefully considered, particularly in the period directly following the start of methylphenidate treatment.

A Latent Profile Analysis of Problematic Media Device Use and Its Association With Executive Function and Behavioral Problem Among Children: A Population-Based Study.

OBJECTIVE: Despite the rapid increase in problematic media device use, relatively little is known about specific characteristics and extent of problematic media device and how they relate to different psychological features. METHODS: Data extracted from the Panel Korea Study for the Child Cohort Study were used. At the age of 9 years, media device addiction severity was assessed using the K-scale, and children's behavioral outcomes were assessed using the Child Behavior Checklist. Among children with problematic media device use (n=339), we performed latent profile analysis using the K-scale to identify subtypes of problematic media device use, and then compared the child behavioral problems and executive function according to the different subtypes of problematic media device use. RESULTS: Children with problematic media device use were divided into class 1 (n=51), class 2 (n=138), and class 3 (n=150). Compared with classes 2 and 3, class 1 had more severe problematic media device use, including daily activity disturbance, withdrawal, and tolerance. Class 1 had the most serious behavioral problems and executive function difficulties among classes. Class 2 had greater daily activity disturbance and tolerance than those of class 3, but executive function showed no significant difference between the two classes. In logistic regression analysis, behavioral problems except for somatization were more common in class 1 than in the control group. CONCLUSION: Results suggest that problematic media device use is associated with significant behavioral problem and executive function difficulties and underscore the need for further clinical and research attention for these specific subgroup members.

Problematic internet use in children according to maternal depression trajectories: A population-based cohort study with 9-year follow-up.

OBJECTIVES: We investigated the association between maternal depression trajectories from pregnancy until 2 years postpartum, and problematic internet use in children at nine years of age. METHODS: A total of 1132 mother-child pairs from the Panel Korea Study for Children were used. Maternal depression was assessed repeatedly using the Kessler scale (K-scale) (during pregnancy, and at 6, 12, and 24 months of age). Problematic internet use was assessed in children 9 years old using the K-scale. The children's behavioral problems were assessed using the Child Behavior Checklist at nine years old. Latent profile analysis was used to identify the group trajectories of maternal depression. We compared the severity of problematic internet use of the children according to the maternal depression trajectories. We also identified behavioral problems in children with problematic internet use in each maternal depression trajectory. RESULTS: Trajectory analysis identified three group trajectories of maternal depression: no symptoms (n = 478), mild symptoms (n = 534), and moderate symptoms (n = 120). The mild and moderate maternal depression trajectory groups were more associated with high-risk internet use in 9-year-old children compared to the non-depressed group. In children with high-risk internet use, more severe behavioral problems were reported when their mothers had depression. CONCLUSION: Maternal depression up to two years after childbirth affected problematic internet use in middle childhood.

Psychopathologic Profiles and Clusters in Tertiary Clinic Referred Patients with Adult Attention Deficit Hyperactivity Disorder: A Person-Centered Analysis.

OBJECTIVE: Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach. METHODS: In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis. RESULTS: Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1. CONCLUSION: Further studies are needed to confirm the relationships observed in the present study.

The impact of maternal personality traits on behavioral problems in preschool-aged children: a population-based panel study in South Korea.

The impact of maternal personality traits on offspring behavioral problems has not been well established. In our study, the association between maternal personality traits and behavioral problems in preschool-aged children was investigated. A total of 192 preschoolers with their mothers, who were part of a population-based panel study in South Korea, were included in the present study. Maternal personality traits were assessed by the Personality Assessment Inventory (PAI) when the children were 1 year old. The Child Behavior Checklist (CBCL) 1.5-5 was used to identify behavioral problems in the children at 4 and 5 years of age. Maternal personality (borderline, somatization) positively correlated with behavioral problems (externalizing, internalizing, and dysregulation) in children. Maternal paranoid personality trait correlated with children's internalizing and dysregulation behavioral problems. Multiple linear regressions showed that maternal borderline trait significantly predicted children's externalizing (B = 0.302, P = 0.001), internalizing (B = 0.211, P = 0.020), and dysregulation problems (B = 0.327, P < 0.001). Similarly, maternal somatization trait predicted children's internalizing problems (B = 0.291, P < 0.001). Maternal borderline and somatization traits showed association with children's behavioral problems. Psychological intervention and support for mothers with these personality traits may be helpful in raising children with behavioral problems.

Maternal depression trajectories and child executive function over 9 years.

BACKGROUND: The present study aimed to assess the relationship between maternal depression trajectories from pregnancy to 2 years after childbirth and childhood behavioral problems and executive function at 9 years. METHODS: Data of mother-child pairs (N = 1191) extracted from the Panel Study on Korean Children (a cohort study) were used. Maternal depression was assessed using the Kessler depression scale during pregnancy and at 6 months, 1 years, and 2 years postpartum. At ages 4, 5, 6, 7, and 9 years, the children's behavioral outcomes were assessed using the Child Behavior Checklist. The children's executive function was assessed using the Executive Function Difficulty Screening Questionnaire at ages 7, 8, and 9 years. We performed a latent profile analysis to identify maternal depression trajectories and compared the children's behavioral problems and executive function among different trajectories. RESULTS: According to maternal depression trajectory, the mother-child pairs were divided into the no symptom (n = 503), mild symptom (n = 558), and moderate symptom (n = 130) groups. Children of mothers with significant depressive symptoms had severe behavioral problems at ages 4, 5, 6, 7, and 9 years. Moreover, compared with children whose mothers were not depressed, those whose mothers had mild or moderate symptoms had impaired executive function at ages 7, 8, and 9 years. CONCLUSIONS: Maternal depression up to 2 years after childbirth affects childhood behavior and executive function into middle childhood.

Incidence of Neutropenia with Valproate, Antipsychotics, and ADHD Medication Combination Treatment in Children and Adolescents.

This study's aim was to investigate whether the incidence of neutropenia was higher in subjects who received a combination pharmacotherapy with valproate (VPA), antipsychotics (APs), and attention deficit hyperactivity disorder (ADHD) medication than in those administered only VPA and APs combination pharmacotherapy. We conducted this study through retrospective review of medical records. We collected the records of 231 children admitted to the National Center for Mental Health. The incidence of neutropenia was significantly higher in the VPA-APs-ADHD combination group than in the other groups (55.2% vs. 25% vs. 12%, VPA + AP + ADHD vs. VPA + AP vs. AP). The presence of the combination of VPA, APs, and ADHD medication was a powerful predictor of neutropenia occurrence after adjusting for age, gender, and body mass index (odds ratio, 6.43; 95% confidence interval, 2.26-18.26; P < 0.001) The combination of VPA, APs, and ADHD medication in children with psychiatric disease appears to increase the incidence of drug-induced neutropenia.

Defining Subtypes in Children with Nail Biting: A Latent Profile Analysis of Personality.

OBJECTIVE: This study aimed to examine personality profiles and behavioral problems of children with nail biting (NB) to gain insight into the developmental trajectory of pathological NB. METHODS: 681 elementary school students were divided into non NB (n=436), occasional NB (n=173) and frequent NB group (n=72) depending on the frequency of NB reported in Child Behavioral Checklist (CBCL). Children's personality was assessed using the Junior Temperament and Character Inventory (JTCI), and behavioral problems were assessed using the CBCL. Latent Profile Analysis (LPA) was performed using JTCI profiles to classify personalities of the children with NB (belonging to frequent and occasional NB group, n=245). RESULTS: For subscale scores of CBCL, the total, internalizing, externalizing, anxious/depressed withdrawn/depressed, depression, thought, rule-breaking, and aggressive behavior problems, were most severe in the frequent NB group followed by occasional NB and non NB group. LPA of personality profile in children with NB revealed four classes ('adaptiveness,' 'high reward dependence,' 'low self-directedness,' and 'maldaptiveness'). The four personality classes demonstrated significant group differences in all of the CBCL subscales. Children who showed low self-directedness and cooperativeness and high novelty seeking and harm avoidance personality profiles demonstrated highest tendency for problematic behavior irrespective of the frequency of NB. CONCLUSION: Children with NB reported significantly more problematic behaviors compared to children without NB. Children with specific personality profile demonstrated higher tendency for problematic behavior irrespective of the frequency of NB. Therefore, accompanying personality profiles should be considered when assessing behavioral problems in children with NB.

Trait Anxiety as a Mediator of the Association between Attention Deficit Hyperactivity Disorder Symptom Severity and Functional Impairment.

OBJECTIVE: Anxiety has been shown to influence functional impairment in patients with attention deficit hyperactivity disorder (ADHD). This study aimed to compare functional impairment in subjects with and without adult ADHD and to investigate the associations among trait anxiety, functional impairment, and ADHD symptom severity. Moreover, the effects of ADHD symptom subtypes on trait anxiety and functional impairment were also examined. METHODS: The sample included 209 adults between the ages of 20 and 31 years. Fifty-one adults received a diagnosis of ADHD, and an additional age, sex-matched group of 51 adults comprised the adult control. Participants were assessed with Conners' Adult ADHD Rating Scales (CAARS), the Beck Depression Inventory (BDI), the Spielberg Trait Anxiety Inventory (STAI-T), and the Sheehan Disability Scale (SDS). The relationships among ADHD severity, anxiety, and functional impairment were investigated using Pearson's correlation analysis. Subtypes of ADHD symptoms that predicted anxiety and functional impairment were investigated using regression analyses. RESULTS: Adult ADHD patients significantly differed from normal control subjects according to BDI, STAI-T, and SDS assessment. Significant positive correlations were noted between ADHD severity, anxiety, and functional impairment. Multiple linear regression analysis confirmed anxiety as a mediator between functional impairment and ADHD CAARS symptom subscales. CONCLUSION: Patients with adult ADHD showed higher levels of anxiety, depression, and functional impairment. Additionally, ADHD symptoms and anxiety impacted subject functional impairment. Our results suggest that anxiety may be a strong mediator between ADHD severity and functional impairment.

Efficacy of Hippotherapy Versus Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial.

OBJECTIVES: Pharmacotherapy among children with attention-deficit/hyperactivity disorder (ADHD) is effective, but many patients suffer from secondary psychiatric problems even after improvement of ADHD core symptoms. Hippotherapy have been used as adjunct treatment options for physical and psychosocial rehabilitation as well as to ameliorate core symptoms. The aim of this study was to investigate the effects of Hippotherapy versus pharmacotherapy for children with ADHD. DESIGN: Thirty-four participants with ADHD were randomly assigned at a 1:1 ratio to either 24 sessions of a twice-weekly hippotherapy or pharmacotherapy. To assess therapeutic effects, the ADHD Rating Scale (ARS) was used pretreatment and posttreatment as the primary outcome measure. Secondary outcomes included the Child Behavior Checklist (CBCL), Self-Esteem Scale (SES), Pediatric Quality of Life Inventory (PedsQL) child and parent report version, Developmental Coordination Disorder Questionnaire (DCDQ), Clinical Global Impressions-Severity (CGI-S), and quantitative electroencephalography. RESULTS: Both groups showed marked improvements in ADHD symptoms, CGI-S. No significant differences between groups were detected regarding treatment outcome except thought problem subscales of CBCL. Twelve weeks of hippotherapy improved attention, impulsivity/hyperactivity, and quality of life. CONCLUSION: This trial is promising, but further studies are required to evaluate the long-term clinical effectiveness of hippotherapy. The study is registered with ClinicalTrials.gov, number NCT 02482649.

The Effects of Attention Problems on Psychosocial Functioning in Childhood Brain Tumor Survivors: A 2-Year Postcraniospinal Irradiation Follow-up.

OBJECTIVE: To examine the psychosocial outcomes and impact of attention problems in survivors of pediatric brain tumor. STUDY DESIGN: The survivors' cognitive functioning was measured using the Wechsler Intelligence Scale for Children. The Child Behavior Checklist-Attention Problems scale was used to screen for attention problems, and participants were classified as having attention problems (n=15) or normal attention (n=36). Psychosocial functioning was examined with the Korean Personality Rating scale for Children (K-PRC) at precraniospinal radiation and at 2-year follow-up. RESULTS: The attention problem group showed significantly higher depression and externalizing symptoms (delinquency, hyperactivity) and more significant impairment in family relationships than did the normal attention group at baseline. At follow-up, the attention problem group demonstrated significantly more delinquency and impaired family and social relationships. With the K-PRC scores, except for the somatization, social relationship subscale, there were significant differences between groups, but not in terms of treatment by time interaction or within time. At follow-up, multiple linear regressions showed that age at diagnosis significantly predicted K-PRC somatization (B=-1.7, P=0.004) and social relationships (B=-1.7, P=0.004), baseline full-scale intelligence quotient predicted K-PRC depression (B=-0.4, P=0.032) and somatization (B=-0.3, P=0.015), and attention problems at baseline predicted K-PRC depression (B=-15.2, P=0.036) and social relationships (B=-11.6, P=0.016). CONCLUSION: Pediatric brain tumor survivors, in particular, patients with attention problems, had worse psychosocial functioning at baseline and follow-up. Attention problems at baseline need to be carefully evaluated in assessing psychosocial functioning of pediatric brain tumor survivors.

Effects of smartphone use with and without blue light at night in healthy adults: A randomized, double-blind, cross-over, placebo-controlled comparison.

Smartphones deliver light to users through Light Emitting Diode (LED) displays. Blue light is the most potent wavelength for sleep and mood. This study investigated the immediate effects of smartphone blue light LED on humans at night. We investigated changes in serum melatonin levels, cortisol levels, body temperature, and psychiatric measures with a randomized, double-blind, cross-over, placebo-controlled design of two 3-day admissions. Each subject played smartphone games with either conventional LED or suppressed blue light from 7:30 to 10:00PM (150 min). Then, they were readmitted and conducted the same procedure with the other type of smartphone. Serum melatonin levels were measured in 60-min intervals before, during and after use of the smartphones. Serum cortisol levels and body temperature were monitored every 120 min. The Profile of Mood States (POMS), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and auditory and visual Continuous Performance Tests (CPTs) were administered. Among the 22 participants who were each admitted twice, use of blue light smartphones was associated with significantly decreased sleepiness (Cohen's d = 0.49, Z = 43.50, p = 0.04) and confusion-bewilderment (Cohen's d = 0.53, Z = 39.00, p = 0.02), and increased commission error (Cohen's d = -0.59, t = -2.64, p = 0.02). Also, users of blue light smartphones experienced a longer time to reach dim light melatonin onset 50% (2.94 vs. 2.70 h) and had increases in body temperature, serum melatonin levels, and cortisol levels, although these changes were not statistically significant. Use of blue light LED smartphones at night may negatively influence sleep and commission errors, while it may not be enough to lead to significant changes in serum melatonin and cortisol levels.

The Effects of Equine-assisted Activities and Therapy on Resting-state Brain Function in Attention-deficit/Hyperactivity Disorder: A Pilot Study.

OBJECTIVE: Equine-assisted activities and therapy (EAA/T) have been used as adjunct treatment options for physical and psychosocial rehabilitation. However, the therapeutic effects on resting-state brain function have not yet been studied. The aim of this study is to investigate the effects of EAA/T on participants with attention-deficit/hyperactivity disorder (ADHD) by comparing resting-state functional magnetic resonance imaging (rs-fMRI) signals and their clinical correlates. METHODS: Ten participants with ADHD participated in a 12-week EAA/T program without any medication. Two rs-fMRIs were acquired for all participants before and after EAA/T. For estimating therapeutic effect, the regional homogeneity (ReHo) method was applied to capture the changes in the regional synchronization of functional signals. RESULTS: After the EAA/T program, clear symptom improvement was found even without medication. Surface-based pairwise comparisons revealed that ReHo in the right precuneus and right pars orbitalis clusters had significantly diminished after the program. Reduced ReHo in the right precuneus cluster was positively correlated with changes in the scores on DuPaul's ADHD Rating Scale-Korean version. CONCLUSION: Our results indicate that EAA/T is associated with short-range functional connectivity in the regions related to the default mode network and the behavioral inhibition system, which are associated with symptom improvement.

Development of an LC-MS/MS method for the simultaneous determination of 25 benzodiazepines and zolpidem in oral fluid and its application to authentic samples from regular drug users.

A simple and reliable analytical method was established and validated for the simultaneous determination of 25 benzodiazepines and zolpidem in oral fluid obtained using the Quantisal™ collection device. The samples were prepared by liquid-liquid extraction with ethyl acetate and analyzed using liquid chromatography-tandem mass spectrometry. The validation parameters included limits of detection and quantification (LOD and LOQ), linearity, accuracy and precision, selectivity, recovery, matrix effects and process efficiency. To investigate the variables associated with collection of oral fluid, drug stability and drug recovery in/from the collection device were also determined. The LOD ranged from 0.01 ng/ml to 0.5 ng/ml and the LOQ ranged from 0.1 ng/ml to 0.5 ng/ml. The results of the intra- and inter-day precision and accuracy were satisfactory, i.e., <10% for precision and within ± 10% for accuracy at a low (LOQ of each analyte) and high concentrations (5 ng/ml). In addition, all analytes were stable under the storage condition of below -20°C for 1 month. Drug recoveries from the collection device were more than 80% (81-95%) except those of clonazepam and flunitrazepam, which were unstable in oral fluid. The developed method was successfully applied to authentic oral fluid specimens obtained from psychiatric patients who take benzodiazepines or zolpidem regularly. As a result, alprazolam, clonazepam, diazepam, flunitrazepam, flurazepam, lorazepam, zolpidem and/or their metabolites were detected at 1-18 h after intake of these drugs. This study will be useful for the analysis of oral fluid samples collected in forensic toxicological cases.