Gut microbial and clinical characteristics of individuals with autism spectrum disorder differ depending on the ecological structure of the gut microbiome.

Understanding the relationship between the gut microbiome and autism spectrum disorder (ASD) is challenging due to the heterogeneous nature of ASD. Here, we analyzed the microbial and clinical characteristics of individuals with ASD using enterotypes. A total of 456 individuals participated in the study, including 249 participants with ASD, 106 typically developing siblings, and 101 controls. The alpha and beta diversities of the ASD, sibling, and control groups did not show significant differences. Analysis revealed a negative association between the Bifidobacterium longum group and the Childhood Autism Rating Scale, as well as a negative association between the Streptococcus salivarus group and the Social Responsiveness Scale (SRS) within the ASD group. When clustered based on microbial composition, participants with ASD exhibited two distinct enterotypes, E1 and E2. In the E2 group, the SRS score was significantly higher, and the Vineland Adaptive Behavior Scale score was significantly lower compared to the E1 group. Machine learning results indicated that the microbial species predicting SRS scores were distinct between the two enterotypes. Our study suggests that the microbial composition in individuals with ASD exhibits considerable variability, and the patterns of associations between the gut microbiome and clinical symptoms may vary depending on the enterotype.

Factors in Parenting Stress in Young Patients With Breast Cancer and Implications for Children's Emotional Development: The PSYCHE Study.

Importance: The number of patients with breast cancer who have children is substantial. However, the emotional burden of this disease and its implication for childhood development remain largely unknown. Objective: To investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children's emotional development. Design, Setting, and Participants: This cross-sectional study involved a survey of females with stage 0 to 3 breast cancer and was conducted from June 2020 to April 2021 in Seoul, South Korea. Participants were aged 20 to 45 years and completed the Center for Epidemiologic Studies Depression-Revised scale and basic questionnaires on demographic and clinical characteristics. Participants with children completed the Korean Parenting Stress Index Short Form (K-PSI-SF), Child Behavior Checklist, Junior Temperament and Character Inventory, and Children's Sleep Habits Questionnaire. Exposure: Having children in patients with breast cancer. Main Outcomes and Measures: Multivariable logistic and linear regression analyses were performed to investigate the association between maternal depression and parenting stress. Results: A total of 699 females (mean [SD] age, 39.6 [4.6] years) were included, of whom 499 had children (mean [SD] age of children, 8.0 [2.7] years). Depression was more common in patients with children (odds ratio [OR], 2.25; 95% CI, 1.01-5.05) and patients who had gonadotropin-releasing hormone treatment (OR, 1.68; 95% CI, 1.15-2.44). Disease duration was inversely associated with depression (OR, 0.85; 95% CI, 0.76-0.96). Cancer-related factors were not associated with the K-PSI-SF score. Having children aged 6 years or older (ß = 3.09; 95% CI, 0.19-5.99); being the sole primary caregiver (ß = -3.43; 95% CI, -5.87 to -0.99); and reporting certain temperament (eg, novelty seeking: ß = 0.58; 95% CI, 0.46-0.71), emotional problems (eg, anxious/depressed: ß = 8.09; 95% CI, 3.34-12.83), and sleeping pattern (eg, bedtime resistance: ß = 0.57; 95% CI, 0.15-0.99) subscale scores in their children were associated with parenting stress. Depression and parenting stress were correlated (ß = 0.56; 95% CI, 0.45-0.66; P < .001). The emotional challenges encountered by children of mothers with breast cancer were not significantly different from reference values. Conclusions and Relevance: This study found that in patients with breast cancer, child-related factors and depression were significantly associated with parenting stress, but breast cancer-related factors were not correlated. The findings suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that tailored counseling and support are needed.

Psychoeducational Profile-Revised, Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Vineland Adaptive Behavior Scale, Second Edition: Comparison of Utility for Developmental Disabilities in Preschool Children.

Objectives: This study aimed to compare the utility of the Psychoeducational Profile-Revised (PEP-R), Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), and Vineland Adaptive Behavior Scale, Second Edition (VABS-II) for evaluating developmental disabilities (DD) in preschool children. Additionally, we examined the correlations between the PEP-R, KWPPSI- IV, and VABS-II. Methods: A total of 164 children aged 37-84 months were assessed. Children's development was evaluated using the PEP-R, K-WPPSIIV, VABS-II, Preschool Receptive-Expressive Language Scale, and Korean Childhood Autism Rating Scale, Second Edition. Results: Of the 164 children, 103 had typical development (TD) and 61 had DD. The mean of the PEP-R Developmental Quotient (DQ), K-WPPSI-IV Full-Scale Intelligence Quotient (FSIQ), and VABS-II Adaptive Behavior Composite (ABC) scores were significantly higher in the TD group than in the DD group (p<0.001). The estimated area under the curve of the PEP-R DQ, K-WPPSI-IV FSIQ, and VABS-II ABC scores was 0.953 (95% confidence interval [CI]=0.915-0.992), 0.955 (95% CI=0.914-0.996), and 0.961 (95% CI=0.932- 0.991), respectively, which did not indicate a statistically significant difference. The PEP-R DQ scores were positively correlated with the K-WPPSI-IV FSIQ (r=0.90, p<0.001) and VABS-II ABC scores (r=0.84, p<0.001). A strong correlation was observed between the KWPPSI- IV FSIQ and VABS-II ABC scores (r=0.89, p<0.001). Conclusion: This study found that the PEP-R, K-WPPSI-IV, and VABS-II effectively distinguished DD from TD in preschool children, and no significant differences in utility were observed between them.

Impact of Comorbid Oppositional Defiant Disorder on the Clinical and Neuropsychological Characteristics of Korean Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: The aim of the present study was to investigate the influence of comorbid oppositional defiant disorder (ODD) on clinical features and neuropsychological profiles of children with attention-deficit/hyperactivity disorder (ADHD). METHODS: We divided the participants into three groups: the ADHD with ODD (ADHD/ODD) (n=36), ADHD without ODD (ADHD/noODD) (n=307), and control groups (n=128). Parents of the participants completed the ADHD Rating Scale, Social Responsiveness Scale (SRS), Korean Personality Rating Scale for Children (K-PRC), and 10-item mania scale from the Parent General Behavior Inventory (P-GBI-10M). Neuropsychological profiles were assessed using the Advanced Test of Attention (ATA), Children's Color Trails Test, and Stroop Color and Word Test. RESULTS: The ADHD/ODD group had more ADHD symptoms and functional impairments in relationships with teachers and peers, and self-esteem than the ADHD/noODD group. The ADHD/ODD group scored higher in Social Communication (p<0.001) and Autistic Mannerisms (p<0.001) subscales of SRS, P-GBI-10M (p<0.001), and Delinquency (p<0.001) and Psychosis (p<0.001) subscales of K-PRC than the ADHD/noODD group. Commission Errors (p<0.001) and Response-Time Variability (p<0.001) in Visual ATA and Commission Errors (p<0.001) in Auditory ATA were significantly higher in the ADHD/ODD group than in the ADHD/noODD group. CONCLUSION: The present study suggests that patients with ADHD with ODD experience more ADHD symptoms and neuropsychological deficits than those with ADHD without ODD. These results also imply that comorbid ODD is associated with greater social impairment and emotional dysregulation.

The Association Between Media-Based Exposure to Nonsuicidal Self-Injury and Emergency Department Visits for Self-Harm.

OBJECTIVE: This study aimed to evaluate the association between media-based exposure to nonsuicidal self-injury (NSSI) and emergency department (ED) visits due to self-harm in Korea, specifically before and after the initial broadcast of the song Barcode, which has an explicit focus on NSSI. METHOD: We used the national emergency department information system to obtain data related to ED visits due to self-harm between January 1, 2014, and December 31, 2018. Using interrupted time series regression analysis, we assessed the monthly ED visits due to self-harm before and after the media-based exposure to NSSI on March 30, 2018. In addition, self-harm methods were assessed. RESULTS: A total of 35,928,834 visits to ED were identified, of which 115,647 were due to self-harm. ED visits due to self-harm showed a significant step increase in the 10- to 14-year-old (ß = 0.883, p = .001), 15- to 19-year-old (ß = 2.941, p < .001), 20- to 24-year-old (ß = 1.997, p = 0.002), and 25- to 29-year-old (ß = 1.438, p = .029) age groups, before and after the media-based exposure to NSSI. The most pronounced increase was observed in male participants aged 20 to 24 years (ß = 1.790, p = .012) and female participants aged 15 to 19 years (ß = 5.158, p < .001). Self-harm by cutting has increased significantly in participants aged 10 to 29 years, and self-harm by poisoning has also increased significantly in participants aged 10 to 19 and 25 to 29 years. CONCLUSION: ED visits due to self-harm increased significantly, especially in adolescents and young adults, following the exposure to NSSI. Responsible media reporting on NSSI and appropriate guidelines would help prevent a further increase in self-harm. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Children's and Parents' Factors That Affect Parenting Stress in Preschool Children With Developmental Disabilities or Typical Development.

OBJECTIVE: This study compared parenting stress in preschool children with developmental disabilities (DD) or typical development (TD). We also investigated children's factors that affect parenting stress. METHODS: A total of 196 preschool children participated in the study (aged 54.8±9.2 months). There were 79 children with DD (59 with autism spectrum disorder, 61 with intellectual disability, 12 with language disorder) and 117 with TD. The high parenting stress and the low parenting stress groups were divided based on the Total Stress of Korean Parenting Stress Index Fourth Edition (K-PSI-4) with an 85-percentile cutoff score. Pearson's correlation analysis was conducted to calculate the correlation between K-PSI-4 and the children's or parents' measures. RESULTS: The difference in parenting stress between DD and TD was significant in the Total Stress of K-PSI-4 (p<0.001). The Total Stress scale of K-PSI-4 represented a modest to strong correlation with cognitive development, adaptive functioning, social communication, and behavioral problems in children with DD. Our results showed that caregivers of children with DD reported higher parenting stress than those with TD. Parenting stress was strongly associated with cognitive development, adaptive functioning, social communication, and behavioral problems in children with DD. Among the children's factors, especially social communication, attention problems, and aggressive behavior had association with caregivers' higher parenting stress. CONCLUSION: These findings suggest the need for early intervention for parenting stress in caregivers by assessing child characteristics, including social cognition, awareness, communication, and inattention and hyperactivity, in the evaluation of children with DD.

Brief Report: Risk Variants Could Inform Early Neurodevelopmental Outcome in Children with Developmental Disabilities.

The aim of this study was to examine genetic variations underlying the early neurodevelopmental outcome of developmental disabilities (DDs). The study cohort consisted of 191 children with DDs. Diagnosis was assessed at baseline and at the index age (72-84 months). Exome sequencing was conducted and putative risk variants were identified. According to the diagnostic improvement, children were categorized into the improvement group (n = 19) and the non-improvement group (n = 172). Compared to the non-improvement group, the improvement group had lower number of risk variants in known DD genes and haploinsufficient genes, and lower number of overall putative risk variants. Our results may serve as a preliminary basis for developing a model that informs clinical outcome by sequencing analysis.

Predictors of Developmental Outcome in 4- to 6-Year-Olds With Developmental Disability.

OBJECTIVE: Studies on the early trajectories of developmental disability (DD) are limited. This study aimed to evaluate the diagnostic stability and developmental trajectories of autism spectrum disorder (ASD) and intellectual disability (ID), and to determine baseline clinical characteristics that affect future diagnosis. METHODS: We analyzed 192 children who were referred for possible DD through retrospective chart review. Clinical diagnosis was assessed once at baseline, aged 2-4, and at follow-up, aged 4-6. The participants' developmental profiles were measured by Psychoeducational Profile-Revised (PEP-R), Vineland Social Maturity Scale (VSMS), Beery-Buktenica Developmental Test of Visual Motor Integration (VMI), and Childhood Autism Rating Scale (CARS). RESULTS: On comparing the diagnostic change, 5% of children were no longer diagnosed as ASD, and 13% of children were no longer diagnosed as ID at follow-up. Trajectories of developmental profiles were compared between children with and without ID at follow-up, and significant time-by-group interaction were observed in PEP-R (p<0.001), VSMS (p<0.001), and VMI (p=0.003) scores, indicating that children without ID at follow-up showed significant improvement over time compared to children with ID. ASD diagnosis (p<0.001) and CARS score (p=0.007) at baseline were significantly associated with ASD at follow-up, while VSMS score (p=0.004) and VMI score (p=0.019) at baseline were significantly associated with ID at follow-up. CONCLUSION: A subset of children lost their diagnosis at follow-up, and such diagnostic change was significantly more common in ID compared to ASD. Baseline autism symptomatology was related to ASD at follow-up, and baseline adaptive and visuo-motor function was related to ID at follow-up.

Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

Viral Anxiety Mediates the Influence of Intolerance of Uncertainty on Adherence to Physical Distancing Among Healthcare Workers in COVID-19 Pandemic.

Introduction: The aims of this study were to examine the mediation effect of viral anxiety of healthcare workers on the influence of their intolerance of uncertainty on the adherence to physical distancing during the COVID-19 pandemic. Methods: An online survey was conducted among 329 healthcare workers (female: 81.4%, nursing professionals: 59.0%, and shift workers: 22.3%) on November 29, 2021. Participants responded to questionnaires on adherence to physical distancing, health beliefs, and perceived social norms, and rating scales of the Stress and Anxiety to Viral Epidemics-6 items (SAVE-6), Patient Health Questionnaire-9 items (PHQ-9), and the Intolerance of Uncertainty-12 items (IUS-12) scale. Results: Adherence to physical distancing of healthcare workers was predicted by perceived benefits of physical distancing (ß = 0.13, p = 0.01), personal injunctive norms (ß = 0.32, p < 0.001), SAVE-6 score (ß = 0.13, p = 0.02), and IUS-12 score (ß = 0.10, p = 0.045) (adjusted R2 = 0.21, F = 22.3, p < 0.001). Viral anxiety mediated the association between intolerance of uncertainty and adherence to physical distancing but not the influence of perceived benefits and personal injunctive norms on adherence to physical distancing. Conclusion: We observed that viral anxiety of healthcare workers mediated the association between intolerance of uncertainty and adherence to physical distancing. During this pandemic, exploring adherence to physical distancing and its predicting factors will be helpful for the safety of healthcare workers and the patients for whom they care.

Mediating Effect of Viral Anxiety and Perceived Benefits of Physical Distancing on Adherence to Distancing Among High School Students Amid COVID-19.

BACKGROUND: The aim of this study is to explore whether high school students' adherence to physical distancing was associated with health beliefs, social norms, and psychological factors during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Overall, 300 high school students participated in this anonymous online survey conducted from October 18-24, 2021. The survey included rating scales such as attitude toward physical distancing during the pandemic, Stress and Anxiety to Viral Epidemics-6 items (SAVE-6), Patient Health Questionnaire-9 items, Satisfaction with Life Scale, and Connor Davidson Resilience Scale 2-items. RESULTS: The results revealed that perceived susceptibility or severity (ß = -0.13, P = 0.038), perceived benefit (ß = 0.32, P < 0.001), descriptive social norms (ß = 0.10, P = 0.041), social injunctive norms (ß = 0.19, P < 0.001), and SAVE-6 (ß = 0.24, P < 0.001) predicted students' adherence to physical distancing (adjusted R² = 0.42, F = 19.2, P < 0.001). Social injunctive norms and personal injunctive norms directly influenced adherence to physical distancing. Viral anxiety, measured by SAVE-6, mediated the association between social injunctive norms and adherence to physical distancing, and perceived benefits mediated the relationship between personal injunctive norms and adherence to physical distancing. The influence of perceived susceptibility or severity on adherence to physical distancing was entirely mediated by perceived benefits or viral anxiety. CONCLUSION: Explaining the rationale or benefits of physical distancing may be important in increasing adherence to physical distancing among high school students.

Psychometric Properties of the Stress and Anxiety to Viral Epidemics-6 Items (SAVE-6) Scale for High School Students During the COVID-19 Pandemic.

Objectives: Owing to the COVID-19 pandemic, high school students have experienced a sudden change of school environment, which may result in difficulties related to mental health. The aim of this study is to estimate the reliability and validity of the Stress and Anxiety to Viral Epidemics-6 Items (SAVE-6) scale among high school students. Methods: A cross-sectional online survey was conducted among 300 high school students. The following scales were administered: the SAVE-6, Generalized Anxiety Disorder-7 Items (GAD-7), and Patient Health Questionnaire-9 Items (PHQ-9). Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted, and the psychometric properties of the SAVE-6 were assessed. Results: The results of the CFA indicated good model fit for the SAVE-6 scale among high school students (χ2/df = 0.485, CFI = 1.000, TLI = 1.010, RMSEA < 0.001, and SRMR = 0.029). In addition, the SAVE-6 scale demonstrated good reliability (Cronbach's alpha = 0.844, McDonald's Omega = 0.848, and split-half reliability = 0.883). The appropriate cut-off score for the SAVE-6 scale was estimated as ≥15, which corresponds to a mild level of anxiety as assessed by the GAD-7 (≥5). Conclusion: The SAVE-6 scale was found to be reliable and valid, and can be used as a tool to assess the stress and anxiety of high school students during the COVID-19 pandemic.

Effect of Screen Time on Physical and Mental Health and Eating Habits During COVID-19 Lockdown in Lebanon.

OBJECTIVE: This study aimed to explore whether screen time and the screen type impacted various health aspects of children, including physical activity (PA), sleep quality, and eating habits. Additionally, we investigated whether children's eating behavior while using electronic devices affects their physical and mental health. METHODS: We conducted an online survey asking for screen use (duration, type, and purpose), PA, eating habits, sleep problems, and level of depression. The participants were children between the ages of 3 and 7 years, and the survey was answered by the participants' parents from March 3 to March 20, 2021. RESULTS: A screen time of ≥2 h in children was associated with various clinical characteristics, such as body mass index (BMI), sleep problems, depression, decreased PA, and unusual eating habits. Children's food eating behavior while using electronic devices was predicted by a total screen time ≥2 h, smartphone screen time ≥2 h, sleep problems, owning electronic devices, and eating unhealthy food. CONCLUSION: There was an interplay among children's PAs, eating behaviors, depression, sleep problems, and screen time in this pandemic era. Therefore, guiding children on the correct use of electronic devices and helping them eat healthy are paramount during this COVID-19 pandemic.

Efficacy of Mobile-Based Cognitive Training Program DoBrain in Preschool Children With or Without Developmental Disabilities: A Randomized, Single-Blind, Active-Controlled Trial.

OBJECTIVE: Mobile-based cognitive training programs can be a viable alternative to in-person interventions, but their efficacies have not been established yet. In this study, we examined the efficacy of DoBrain, a mobile-based cognitive training program designed for children with developmental disabilities (DDs), in comparison with general educational apps named Junior Naver and Kakao Kids. METHODS: Children aged 34 to 77 months were recruited and randomized at a 1:1 ratio to use DoBrain or general educational apps. Each group used the assigned app on a daily basis at home for 30 minutes for 24 weeks. Parents were instructed to help the children with the app usage. A total of 166 children completed the post-test visit (DoBrain group, n=85, 55.4±8.7 months old; general educational app group, n=81, 53.7±9.9 months old). The primary outcome was cognitive development measured by Psychoeducational Profile-Revised (PEP-R), administered at baseline and at post-test. RESULTS: DoBrain had no superior effect over general educational apps on the PEP-R Developmental Quotient. When the changes before and after app usage were compared, the DoBrain group and the general educational app group both showed declines in imitation (adjusted p=0.049 and 0.022), perception (adjusted p=0.004 and <0.001), and gross motor (adjusted p=0.003 and 0.002) domains of the PEP-R. Among the DoBrain group, children with DD showed a significantly greater gain in the eye-hand coordination domain of PEP-R compared with those without DD (adjusted p=0.047). CONCLUSION: DoBrain did not show a superior effect over general educational apps on overall cognitive development in preschool children, regardless of the presence of DD. Careful monitoring of the negative effect of mobile-based cognitive training programs is necessary.

Sleep difficulties and related behavioral problems in Korean preschool children.

OBJECTIVES: Sleep difficulties are associated with various behavioral problems and cognitive development, but the association has not been thoroughly evaluated in preschoolers with and without developmental disability (DD). The aim of this study was to compare the behavioral and cognitive characteristics of poor and good sleepers with and without DD in a community-based sample of preschool children. METHODS: We recruited 196 children aged 34-77 months from community-based daycare centers, kindergartens, and special education centers. Children were classified as poor sleepers with DD (n = 23), poor sleepers without DD (n = 23), good sleepers with DD (n = 64), and good sleepers without DD (n = 94). Poor sleepers were defined based on Children's Sleep Habits Questionnaire Total Sleep Disturbance Score (CSHQ TSDS) cutoff of >52. RESULTS: When compared to good sleepers with DD, poor sleepers with DD scored significantly higher on the Attention Problems (p = 0.005) and Aggressive Behaviors (p = 0.001) subscales of the CBCL, indicating greater difficulty. Caregivers of the poor sleepers with DD reported more depressive symptoms (p = 0.028) and more stress related to the child (p = 0.002) and the parent (p = 0.045) than caregivers of the good sleepers with DD. On the other hand, when compared to good sleepers without DD, poor sleepers without DD scored significantly higher only on the Anxious/Depressed subscale (p = 0.045) of the CBCL. Cognitive development and adaptive functioning were not significantly different between poor and good sleepers with and without DD. Among the subscales of the CSHQ, the Sleep Onset Delay showed strongest correlation with behavioral measures of the children and distress of the caregivers. CONCLUSION: Externalizing problems such as aggressive behaviors, rather than cognitive development, are associated with sleep difficulties in preschool children with DD.

Polymorphism in the MAGI2 Gene Modifies the Effect of Amyloid ß on Neurodegeneration.

INTRODUCTION: A weak association between amyloid ß (Aß) deposition and neurodegeneration biomarkers, such as brain atrophy, has been repeatedly reported in a subset of patients with Alzheimer disease, suggesting individual differences in response to Aß deposition. METHODS: Here, we performed a genome-wide interaction study to identify single-nucleotide polymorphism (SNP) that modify the effect of Aß (measured by 18F-florbetapir positron emission tomography) on brain atrophy (measured by cortical thickness using magnetic resonance imaging). We used magnetic resonance imaging, positron emission tomography, cerebrospinal fluid, and genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database [discovery cohort, ADNI-GO/2 (n=723) and replication cohort, ADNI-1 (n=129)]. RESULTS: We identified a genome-wide suggestive interaction of rs3807779 SNP (ß=-0.14, SE=0.029, P=9.08×10-7) in the discovery cohort. The greater dosage of rs3807779 SNP increased the detrimental effect of Aß deposition on cortical thickness. In replication analyses, the congruent results were replicated to confirm our findings. Furthermore, rs3807779 SNP augmented the detrimental effect of Aß deposition on cognitive function. Genetic profiling showed that rs3807779 has chromatin interactions with the promoter region of MAGI2 gene, suggesting its association with MAGI2 expression. CONCLUSIONS: These findings demonstrate that subjects carrying the rs3807779 SNP are more susceptible to Aß-related neurodegeneration.

Genetic variants beyond amyloid and tau associated with cognitive decline: A cohort study.

OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with cognitive decline independent of ß-amyloid (Aß) and tau pathology in Alzheimer disease (AD). METHODS: Discovery and replication datasets consisting of 414 individuals (94 cognitively normal control [CN], 185 with mild cognitive impairment [MCI], and 135 with AD) and 72 individuals (22 CN, 39 with MCI, and 11 with AD), respectively, were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Genome-wide association analysis was conducted to identify SNPs associated with individual cognitive function (measured with the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale-Cognitive Subscale ) while controlling for the level of Aß and tau (measured as CSF phosphorylated-tau/Aß1-42). Gene ontology analysis was performed on SNP-associated genes. RESULTS: We identified 1 significant (rs55906536, ß = -1.91, standard error 0.34, p = 4.07 × 10-8) and 4 suggestive variants on chromosome 6 that were associated with poorer cognitive function. Congruent results were found in the replication data. A structural equation model showed that the identified SNP deteriorated cognitive function partially through cortical thinning of the brain in a region-specific manner. Furthermore, a bioinformatics analysis showed that the identified SNPs were associated with genes related to glutathione metabolism. CONCLUSIONS: In this study, we identified SNPs related to cognitive decline in a manner that could not be explained by Aß and tau levels. Our findings provide insight into the complexity of AD pathogenesis and support the growing literature on the role of glutathione in AD.

Functional fine-mapping of noncoding risk variants in amyotrophic lateral sclerosis utilizing convolutional neural network.

Recent large-scale genome-wide association studies have identified common genetic variations that may contribute to the risk of amyotrophic lateral sclerosis (ALS). However, pinpointing the risk variants in noncoding regions and underlying biological mechanisms remains a major challenge. Here, we constructed a convolutional neural network model with a large-scale GWAS meta-analysis dataset to unravel functional noncoding variants associated with ALS based on their epigenetic features. After filtering and prioritizing of candidates, we fine-mapped two new risk variants, rs2370964 and rs3093720, on chromosome 3 and 17, respectively. Further analysis revealed that these polymorphisms are associated with the expression level of CX3CR1 and TNFAIP1, and affect the transcription factor binding sites for CTCF, NFATc1 and NR3C1. Our results may provide new insights for ALS pathogenesis, and the proposed research methodology can be applied for other complex diseases as well.

Psychological Impact of Quarantine on Caregivers at a Children's Hospital for Contact with Case of COVID-19.

Quarantine often provokes negative psychological consequences. Thus, we aimed to identify the psychological and behavioral responses and stressors of caregivers quarantined with young patients after a close contact to a coronavirus disease 2019 case at a children's hospital. More than 90% of the caregivers reported feelings of worry and nervousness, while some of them reported suicidal ideations (4.2%), and/or homicidal ideations (1.4%). Fear of infection of the patient (91.7%) and/or oneself (86.1%) were most frequently reported stressors. A multidisciplinary team including infection control team, pediatrician, psychiatrist, nursing staff and legal department provided supplies and services to reduce caregiver's psychological distress. Psychotropic medication was needed in five (6.9%), one of whom was admitted to the psychiatry department due to suicidality. Quarantine at a children's hospital makes notable psychological impacts on the caregivers and a multidisciplinary approach is required.

Clinical and Neuropsychological Characteristics of ADHD According to DSM-5 Age-of-Onset Criterion in Korean Children and Adolescents.

Objective: The aim of this study was to compare the clinical features and neuropsychological profiles of children and adolescents with ADHD according to the age-of-onset defined in the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). Method: We compared the following three groups: early-onset ADHD group (onset before age 7, n = 86), late-onset ADHD group (onset between ages 7 and 12, n = 58), and the control group (n = 88). Results: Both early-onset and late-onset ADHD groups had more symptoms and functional impairments than the control group. Also, both ADHD groups scored higher on ADHD Rating Scale, Parent General Behavior Inventory, majority of the subscales of Social Responsiveness Scale, Hyperactivity subscale of Korean Personality Rating Scale for Children, and Omission Errors of Visual Continuous Performance Test compared with the control group. Conclusion: Our results support the extension of age-of-onset criterion made in DSM-5.