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Jinuk Song,1 Doug Hyun Han,1 Sun Mi Kim,1 Ji Sun Hong,1 Kyung Joon Min,1 Jae Hoon Cheong,2 Bung Nyun Kim3 1Department of Psychiatry, Chung Ang University Hospital, 2Uimyung Research Institute for Neuroscience, Samyook University, 3Department of Psychiatry, Seoul National Hospital, Seoul, South Korea Background: Although schizophrenia and bipolar disorder (BD) are classified as different disease entities, they share critical pathognomonic symptoms in terms of hallucination and delusion. Because the characteristics of clinical symptoms are not sufficient to differentiate schizophrenia from BD, several studies have applied brain imaging methods to provide biological evidence of differences. We compared gray matter (GM) volume differences in schizophrenia and BD patients and examined volumetric differences associated with hallucination and delusion in these two groups.Methods: Ninety-three schizophrenia patients and 75 BD patients who were followed for at least 3 years in an outpatient department were recruited for this study. Magnetic resonance data from 71 schizophrenia patients and 44 BD patients were obtained using a 3.0 T scanner. Volumetric differences were analyzed using Matlab 8.0.0 and SPM8 software.Results: The results showed that delusion symptoms were negatively correlated with GM volume within both frontal and both temporal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal cortices in the BD group. Hallucination symptoms were negatively correlated with GM volume within the bilateral frontal, bilateral temporal, and left parietal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal, right parietal, occipital, and insular cortices in the BD group.Conclusion: Delusions in schizophrenia were correlated with GM volume in multiple brain regions, including the frontal, temporal, and parietal cortices, compared to those in patients with BD. Hallucination was associated with temporal lobe GM volume in patients with schizophrenia and with insular cortex GM volume in patients with BD. Keywords: schizophrenia, bipolar disorder, delusion, hallucination, voxel-based morphometry

Studies on early life ambient air pollution exposures and childhood thyroid function are scarce. This study aimed to evaluate the relationships between early life fine particulate matter (≤2.5 μm; PM 2.5 ) and nitrogen dioxide (NO 2 ) exposures and thyroid function in children. We measured the levels of thyrotropin, triiodothyronine, and free thyroxine in children (n = 684) residing in a rural Korean area at age 2, 4, 6, or 8 years from 2012 to 2020 in the Environment and Development of Children cohort. The relationship between residential average exposure levels of PM 2.5 and NO 2 during pregnancy and 1-year average levels before visit and thyroid function during childhood were analyzed. Inverse association between increases of 10 μg/m 3 in PM 2.5 during the first trimester and thyrotropin levels at aged 4 (β, -0.12; 95% CI: -0.22, -0.02) and 6 years (β, -0.16; 95% CI: -0.26, -0.06) were observed. No association was found between PM 2.5 exposure during the second and third trimester and childhood TSH levels. Childhood PM 2.5 exposure was positively associated with thyrotropin rise at aged 4 (β, 0.2; 95% CI: 0.06, 0.35) and 6 years (β, 0.16; 95% CI: 0.02, 0.29) and inversely related with free thyroxine levels at aged 8 years (β, -0.04; 95% CI: -0.07, -0.01). No relationship between NO 2 exposure and thyroid function was found. In conclusion, association between PM 2.5 exposure and childhood thyrotropin levels varied depending on exposure timing. Early gestational exposure showed an inverse relationship, whereas childhood exposure were positively associated with childhood thyrotropin levels. The long-term effects of early life air pollution exposure and underlying mechanisms should be investigated in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Studies on the combined effects of persistent and non-persistent endocrine-disrupting chemicals (EDCs) on puberty are insufficient. To date, no studies have analyzed breast development at age 8 years, a key criterion for determining precocious puberty. We investigated the relationship between prenatal or childhood exposure to EDC mixtures and early thelarche, defined as breast development before age 8 years in girls., Methods: This prospective study included 211 girls with data on prenatal and 8-year-old exposure of cadmium (Cd), lead, mercury, bisphenol-A (BPA), 3-phenoxybenzoic acid, and three phthalate metabolites from the Environment and Development of Children cohort. Prenatal exposure was assessed through samples from pregnant women at 14-27th weeks of gestation. Tanner staging was assessed by a pediatric endocrinologist. The relationship between single and mixed chemical exposures and outcomes was assessed using logistic regression, generalized additive models (GAM), and Bayesian kernel machine regression (BKMR) models., Results: Early thelarche was observed in 42 (19.9%) girls at age 8 years. In the logistic regression models, the risk of early thelarche increased with increased exposure to Cd in their mothers (adjusted odds ratio [aOR] per interquartile range [IQR] = 1.80, 95% confidence interval [CI] 1.23-2.65) but decreased with prenatal BPA exposure (aOR per IQR = 0.57, 95% CI 0.35-0.92). None of the 8-year-old chemical exposures was associated with early thelarche. In the GAM, early thelarche was positively correlated with prenatal Cd and inversely associated with prenatal BPA exposure (p = 0.004 for Cd and p = 0.036 for BPA). In the BKMR models, an increase in log-transformed prenatal Cd concentrations from the 25th to 75th percentile was associated with an increase in the estimated probability of early thelarche at age 8 years (risk difference: 0.46 [95% credible interval: 0.04-0.88]) when other chemicals were set at their median values., Conclusions: Considering the combined effects of persistent and non-persistent chemical mixtures, maternal Cd exposure during the second trimester may be associated with early thelarche in 8-year-old girls., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM 2.5 ) and < 10 µm (PM 10 ) in an aerodynamic diameter], nitrogen dioxide (NO 2 ), ozone (O 3 ), carbon monoxide (CO), and sulfur dioxide (SO 2 ) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants., Results: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM 2.5 (4.56 μg/m 3 ) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM 2.5 (4.76 μg/m 3 ) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM 10 (4.30 μg/m 3 ) and O 3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively., Conclusion: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Differentiating between the diagnoses of mood disorders and other psychiatric disorders, and predicting treatment response in depression has long been a concern for clinicians. Machine learning (ML) is one part of artificial intelligence that focuses on instructing computers to mimic the cognitive abilities of the human brain through training. This study will review the research on the use of ML techniques to differentiate diagnoses and predict treatment responses in mood disorders based on electroencephalography (EEG) data. There have been several attempts to differentiate between the diagnoses of bipolar disorder and major depressive disorder , mood disorders, and other psychiatric disorders using ML techniques found on EEG markers. Previous studies have shown that accuracy varies depending on which EEG markers are used, the sample size, and the ML technique. Also, precise and improved ML approaches can be developed by adapting the various feature selection and validation methods that reflect each disease's characteristics. Although ML faces some limitations and challenges in solving for consistent and improved accuracy in the diagnosis and treatment of mood disorders, it has a great potential to understand mood disorders better and provide valuable tools to personalize both identification and treatment.

This study aimed to determine whether urinary creatinine excretion rate (CER), a marker of muscle mass, is associated with diabetic retinopathy in individuals with type 2 diabetes and to ascertain whether this putative association depends on body mass index (BMI). This cross sectional study evaluated 2035 individuals with type 2 diabetes. Twenty-four-hour urine was collected. Individuals with diabetic retinopathy had lower CER and BMI values than those without. Patients in higher CER quartiles had higher BMI values and a lower prevalence of diabetic retinopathy. A significant relationship between CER and diabetic retinopathy persisted, even after adjusting for traditional risk factors, including glycated hemoglobin, diabetes duration, and hypertension, in multivariable analysis. Further adjustment for BMI did not significantly alter the association between CER and diabetic retinopathy. This study suggests that CER is inversely associated with diabetic retinopathy in individuals with type 2 diabetes, and this association is independent of BMI., (© 2024. The Author(s).)

With the global increase in life expectancy, there has been a rise in the incidence of cognitive impairments attributed to diverse etiologies. Notably, approximately 50% of individuals diagnosed with mild cognitive impairment (MCI) progress to dementia within 3 years. However, the precise mechanisms underlying MCI remain elusive. Therefore, this study aimed to elucidate potential mechanisms implicated in MCI utilizing Per2 knockout (KO) mice, which have previously been shown to have cognitive deficits. Behavioral (Y-maze, Barnes maze) and molecular (electrophysiology, RNA sequencing, western blot, and immunofluorescence) experiments were conducted in Per2 KO and wild-type (WT) mice. Per2 KO mice exhibited impaired spatial working memory in the Y-maze and Barnes maze. However, there were no significant group differences in hippocampal long-term potentiation (LTP) between Per2 KO and WT mice, whereas striatal LTP in Per2 KO mice was lower compared to WT mice. In RNA sequencing analysis, 58 genes were downregulated and 64 genes were upregulated in the striatum of Per2 KO mice compared to WT mice. Among the differentially expressed genes, four genes (Chrm2, EphB2, Htr1b, Oprm1) were identified. Optimal expression levels of EPHB2 and OPRM1 were found to significantly enhance cognitive performance in mice. Additionally, Per2 KO mice exhibited reduced EPHB2-NMDAR-LTP and OPRM-mTOR signaling, along with elevated amyloid beta (Aβ) levels, when compared to WT mice. However, these alterations were reversed upon administration of morphine treatment. Striatal OPRM1-mTOR signaling, EPHB2-NMDAR-LTP signaling, and Aβ expression levels may exert a combined effect on MCI under the control of Per2 expression., (© 2024. The Author(s).)

This study utilized arterial spin labeling-magnetic resonance imaging (ASL-MRI) to explore the developmental trajectory of brain activity associated with attention deficit hyperactivity disorder (ADHD). Pulsed arterial spin labeling (ASL) data were acquired from 157 children with ADHD and 109 children in a control group, all aged 6-12 years old. Participants were categorized into the age groups of 6-7, 8-9, and 10-12, after which comparisons were performed between each age group for ASL analysis of cerebral blood flow (CBF). In total, the ADHD group exhibited significantly lower CBF in the left superior temporal gyrus and right middle frontal gyrus regions than the control group. Further analysis revealed: (1) The comparison between the ADHD group (N = 70) aged 6-7 and the age-matched control group (N = 33) showed no statistically significant difference between. (2) However, compared with the control group aged 8-9 (N = 39), the ADHD group of the same age (N = 53) showed significantly lower CBF in the left postcentral gyrus and left middle frontal gyrus regions. (3) Further, the ADHD group aged 10-12 (N = 34) demonstrated significantly lower CBF in the left superior occipital region than the age-matched control group (N = 37). These age-specific differences suggest variations in ADHD-related domains during brain development post age 6-7., (© 2024. The Author(s).)

The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP; < 28 weeks of gestation) and very-to-late (V-LP; ≥ 28 and < 37 weeks of gestation) preterm infants at term-equivalent age to predict 2-year neurodevelopmental outcomes. Using MRI and diffusion MRI on 62 EP and 131 V-LP infants, we built a multimodal feature set for volumetric and structural network analysis. We employed linear and nonlinear machine learning models to predict the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores, assessing predictive accuracy and feature importance. Our findings revealed that models incorporating local connectivity features demonstrated high predictive performance for BSID-III subsets in preterm infants. Specifically, for cognitive scores in preterm (variance explained, 17%) and V-LP infants (variance explained, 17%), and for motor scores in EP infants (variance explained, 15%), models with local connectivity features outperformed others. Additionally, a model using only local connectivity features effectively predicted language scores in preterm infants (variance explained, 15%). This study underscores the value of multimodal feature sets, particularly local connectivity, in predicting neurodevelopmental outcomes, highlighting the utility of machine learning in understanding microstructural changes and their implications for early intervention., (© 2024. The Author(s).)

Objectives: Non-suicidal self-injury (NSSI) and suicidal behavior, including suicidal ideation (SI) and suicide attempts, are important predictors of suicide in adolescents. This study aimed to investigate the associations between NSSI, SI, NSSI+SI, mental health problems, and family factors in Korean adolescents in Jeju Island, with an emphasis on key findings., Methods: A total of 561 adolescents completed self-report questionnaires regarding demographics, NSSI, SI, suicidal behavior, perceived family functioning, and mental health problems, which were assessed using Center for Epidemiological Studies Depression Scale for Children, Screen for Children Anxiety-Related Disorders (SCARED), and Youth Self-Report (YSR). Data were analyzed using descriptive statistics, one-way analysis of variance, chi-square test, post-hoc analyses, and multivariate logistic regression., Results: In this study, 22.3% of adolescents reported either NSSI or SI, with 5.5% reporting NSSI and 20.7% reporting SI. Combined (NSSI+SI) group showed a significantly higher SCARED score, anxiety/depression, thought problems, attention problem, and rule breaking on YSR than did the SI only group. Higher level of depression and anxiety were significantly associated with NSSI and SI. Female sex and perceived family dissatisfaction were significantly associated factors for SI, but not for NSSI in multivariate logistic regression., Conclusion: This study provides insights into the clinical characteristics and associated factors among adolescents with NSSI, SI, and NSSI+SI in Jeju Island. Identifying these results can inform the development of targeted prevention and intervention strategies to mitigate the negative consequences of these behaviors and contribute to a better understanding of the role of family in this context., Competing Interests: Conflicts of Interest Duk-Soo Moon, a contributing editor of the Journal of the Korean Academy of Child and Adolescent Psychiatry, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Aberrant intrinsic brain networks are consistently observed in individuals with autism spectrum disorder. However, studies examining the strength of functional connectivity across brain regions have yielded conflicting results. Therefore, this study aimed to investigate the functional connectivity of the resting brain in children with low-functioning autism, including during the early developmental stages. We explored the functional connectivity of 43 children with autism spectrum disorder and 54 children with typical development aged 2 to 12 years using resting-state functional magnetic resonance imaging data. We used independent component analysis to classify the brain regions into six intrinsic networks and analyzed the functional connectivity within each network. Moreover, we analyzed the relationship between functional connectivity and clinical scores. In children with autism, the under-connectivities were observed within several brain networks, including the cognitive control, default mode, visual, and somatomotor networks. In contrast, we found over-connectivities between the subcortical, visual, and somatomotor networks in children with autism compared with children with typical development. Moderate effect sizes were observed in entire networks (Cohen's d = 0.43-0.77). These network alterations were significantly correlated with clinical scores such as the communication sub-score (r = - 0.442, p = 0.045) and the calibrated severity score (r = - 0.435, p = 0.049) of the Autism Diagnostic Observation Schedule. These opposing results observed based on the brain areas suggest that aberrant neurodevelopment proceeds in various ways depending on the functional brain regions in individuals with autism spectrum disorder., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to develop a microelectrode array-based neural probe that can record dopamine activity with high stability and sensitivity. To mimic the high stability of the gold standard method (carbon fiber electrodes), the microfabricated platinum microelectrode is coated with carbon-based nanomaterials. Carboxyl-functionalized multi-walled carbon nanotubes (COOH-MWCNTs) and carbon quantum dots (CQDs) were selected for this purpose, while a conductive polymer like poly (3-4-ethylene dioxythiophene) (PEDOT) or polypyrrole (PPy) serves as a stable interface between the platinum of the electrode and the carbon-based nanomaterials through a co-electrodeposition process. Based on our comparison between different conducting polymers and the addition of CQD, the CNT-CQD-PPy modified microelectrode outperforms its counterparts: CNT-CQD-PEDOT, CNT-PPy, CNT-PEDOT, and bare Pt microelectrode. The CNT-CQD-PPy modified microelectrode has a higher conductivity, stability, and sensitivity while achieving a remarkable limit of detection (LOD) of 35.20 ± 0.77 nM. Using fast-scan cyclic voltammetry (FSCV), these modified electrodes successfully measured dopamine's redox peaks while exhibiting consistent and reliable responses over extensive use. This electrode modification not only paves the way for real-time, precise dopamine sensing using microfabricated electrodes but also offers a novel electrochemical sensor for in vivo studies of neural network dynamics and neurological disorders.

Objective: This study aimed to develop and validate a comprehensive self-report questionnaire to assess emotional and behavioral problems and psychological trauma in maltreated children., Methods: The Mental Health Scale for Maltreated Children (MHS-MC) was constructed to encompass five major symptoms (depression, anxiety, inattention/hyperactivity/impulsivity, aggression/defiance, and psychological trauma) prevalent in maltreated children. Critical items and ego-resilience subscale were also devised to increase clinical utility. After informed consent, 205 children (maltreated children, n=157, 76.6%) were recruited nationwide, and they answered a package of self-report measures, including the MHS-MC. Reliability, construct validity, concurrent validity, and criterion-related validity were examined to explore the psychometric properties., Results: The reliability was good to excellent. Confirmatory factor analysis yielded a five-factorial solution for the symptom subscales supporting construct validity. In logistic regression, the total scores of the MHS-MC predicted membership in the maltreated group. Criterion-related validity was generally satisfactory in that all subscales of the MHS-MC showed significant correlations with relevant measures in the expected direction., Conclusion: This is the first attempt to develop a comprehensive psychological scale based on nationwide data collected from maltreated Korean children. We hope that the continued standardization of this scale will contribute to evidence-based clinical and policy decisionmaking for maltreated children.

Background: Bisphenol A (BPA) is known as an obesogenic endocrine disruptor. Bisphenol S (BPS) and F (BPF) are substitutes that have recently replaced BPA., Objectives: To investigate the relationships of urinary bisphenols (BPA, BPS and BPF) with adiposity measurements (obesity, BMI z-score, and fat mass), serum adipokine levels (adiponectin and leptin), and adiponectin/leptin ratio (A/L ratio) in 6- and 8-year-old children., Methods: A total of 561 children who participated in the Environment and Development of Children cohort (482 and 516 children visited at age 6 and 8, respectively) at Seoul National University Children's Hospital during 2015-2019 were included. Urinary BPA levels were log-transformed. BPS levels were categorized into three groups (non-detected, lower-half, and higher-half of detected), and BPF levels were classified into two groups (non-detected and detected)., Results: The urinary BPS higher-half group had a higher BMI z-score (β = 0.160, P= 0.044), higher fat mass (β = 0.104, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (β = 0.074, P< 0.001), lower adiponectin concentration (β =- 0.069, P< 0.001), higher leptin concentration (β = 0.360, P< 0.001), and lower A/L ratio (β =- 0.428, P< 0.001) compared with the non-detected group. The BPA levels showed no consistent associations with outcomes, except for isolated associations of BPA at age 6 with a higher BMI z-score at age 6 (P= 0.016) and leptin at age 8 (P= 0.021)., Conclusions: Increased exposure to BPS and BPF is associated with higher fat mass and leptin concentration, lower serum adiponectin, and lower A/L ratio in children. These findings suggest potential adverse effects of BPA substitutes on adiposity and adipokines. No consistent association of BPA exposure with outcomes could be partly explained by the decreasing BPA levels over time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: : To examine the effect of mobile neurofeedback training on the clinical symptoms, attention abilities, and execution functions of children with attention deficit hyperactivity disorder (ADHD)., Methods: : The participants were 74 children with ADHD aged 8-15 years who visited the Department of Child and Adolescent Psychiatry at Seoul National University Children's Hospital. The participants were randomly assigned to the mobile neurofeedback (n = 35) or control (sham; n = 39) group. Neurofeedback training was administered using a mobile app (equipped with a headset with a 2-channel electroencephalogram [EEG] sensor) for 30 min/day, 3 days/week, for 3 months. Children with ADHD were individually administered various neuropsychological tests, including the continuous performance test, Children's Color Trails Test-1 and 2, and Stroop Color and Word Tests. The effects of mobile neurofeedback were evaluated at baseline and at 3 and 6 months after treatment initiation., Results: : Following treatment, both mobile neurofeedback-only and sham-only groups showed significant improvements in attention and response inhibition. In the visual continuous performance test, omission errors decreased to the normal range in the mobile neurofeedback-only group after training, suggesting that mobile neurofeedback effectively reduced inattention in children with ADHD. In the advanced test of attention, auditory response times decreased in the mobile neurofeedback + medication group after training, but increased in the sham+medication group. Overall, there were no significant between-group differences in other performance outcomes., Conclusion: : Mobile neurofeedback may have potential as an additional therapeutic option alongside medication for children with ADHD.

Adversity may bring about both negative and positive changes in psychological adaptation. Although there is mounting evidence regarding the psychological distress during the pandemic, the other side of posttraumatic change, posttraumatic growth (PTG) and its predictors are relatively underexamined. Moreover, there is a paucity of longitudinal investigations that examined intra- and interpersonal predictors responsible for both sides of psychological adaptation. Therefore, this study comprehensively examined the longitudinal relationship among cognitive processing, social support, and adaptation during the pandemic using a moderated mediation model. Specifically, it was tested whether two types of event-related rumination mediated the link between perceived stress and ambilateral adaptational outcomes, and whether social support moderated the mediating pathways of ruminations on adaptation. After informed consent, a representative sample of adults was followed up for over a year, and answered a package of online questionnaires. The results showed that intrusive rumination prospectively predicted greater psychological distress and less PTG in response to stress, whereas deliberate rumination led to less psychological distress and more PTG over time. As predicted, the indirect protective effect of deliberate rumination was stronger when perceived social support was higher. This longitudinal study highlighted the core factors responsible for continued suffering and personal growth during the pandemic. These results have both practical and clinical implications for mental healthcare in the post-COVID era, when the heterogeneity of psychological adaptation increases and preparation for the next pandemic is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Kang and Park.)

Parents of children with autism spectrum disorder (ASD) often encounter unique challenges when attempting to understand their children's challenging behaviors such as self-injury, aggression, noncompliance, and stereotypies. In this study, we aimed to analyze and clarify the definition of challenging behaviors in individuals with ASD, identify the variables associated with challenging behaviors, and determine the function of these behaviors. Systematic observation and data collection are crucial to understand the functions of specific behaviors exhibited by individuals with ASD based on their antecedents and consequences. Knowledge regarding these will enable clinicians to develop and implement effective interventions. Additionally, the treatment approach should aim for generalization to improve the quality of lives of both children with ASD and their caregivers., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Under the Ministry of Health and Welfare of the Republic of Korea, the National Autism and Developmental Disorder Centers for people with developmental disabilities are gradually expanding. The headquarters of the National Autism and Developmental Disorder Center provides support for education, training, and research, and several centers have been effectively operating since 2020. This study aimed to provide practical recommendations and guidelines for specialists such as clinical psychologists, child psychiatrists, allied professionals, community workers, and related administrators. It was developed as a guideline to promote early diagnosis, provide important information on integrated treatment, and assist people with developmental disabilities in Korea to make the best decisions for their quality of life., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

Objective: Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea., Methods: Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100-299 μg/L), mild excess (300-499 μg/L), moderate excess (500-999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references., Results: The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1-9.2) and aOR = 3.1 (95% CI: 1.2-8.3), respectively; age-specific criteria) than the iodine-adequate group., Conclusions: Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.

Objective: : Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adults characterized by cognitive and emotional self-control deficiencies. Previous functional near-infrared spectroscopy (fNIRS) studies found significant group differences between ADHD children and healthy controls during cognitive flexibility tasks in several brain regions. This study aims to apply a machine learning approach to identify medication-naive ADHD patients and healthy control (HC) groups using task-based fNIRS data., Methods: : fNIRS signals from 33 ADHD children and 39 HC during the Stroop task were analyzed. In addition, regularized linear discriminant analysis (RLDA) was used to identify ADHD individuals from healthy controls, and classification performance was evaluated., Results: : We found that participants can be correctly classified in RLDA leave-one-out cross validation, with a sensitivity of 0.67, specificity of 0.93, and accuracy of 0.82., Conclusion: : RLDA using only fNIRS data can effectively discriminate children with ADHD from HC. This study suggests the potential utility of the fNIRS signal as a diagnostic biomarker for ADHD children.

Introduction: Since the Coronavirus disease 2019 (COVID-19), public safety measures, including social distancing and school closures, have been implemented, precipitating psychological difficulties and heightened online activities for adolescents. However, studies examining the impact of the pandemic on adolescent mental health and their coping strategies in Asian countries are limited. Further, most studies have used survey measures to capture mental health challenges so far. Accordingly, this study aimed to examine the psychological challenges South Korean adolescents experienced and their coping strategies during the pandemic using the Natural Language Processing (NLP) and Text mining (TM) technique on adolescents' social media texts/posts., Methods: The data were gathered from social media texts/posts such as online communities, Twitter, and personal blogs from January 1, 2019, to October 31, 2021. The 12,520,250 texts containing keywords related to adolescents' common psychological difficulties reported during the pandemic, including self-harm, Attention-Deficit/Hyperactivity Disorders (ADHD), and insomnia, were analyzed by TM, NLP using information extraction, co-occurrence and sentiment analysis. The monthly frequency of the keywords and their associated words was also analyzed to understand the time trend., Results: Adolescents used the word "self-harm" in their social media texts more frequently during the second wave of COVID-19 (August to September 2020). "Friends" was the most associated word with "self-harm." While the frequency of texts with "Insomnia" stayed constant throughout the pandemic, the word "ADHD" was increasingly mentioned in social media. ADHD and insomnia were most frequently associated with ADHD medications and sleeping pills, respectively. Friends were generally associated with positive words, while parents were associated with negative words., Conclusion: During COVID-19, Korean adolescents often expressed their psychological challenges on social media platforms. However, their coping strategies seemed less efficient to help with their difficulties, warranting strategies to support them in the prolonged pandemic era. For example, Korean adolescents shared psychological challenges such as self-harm with friends rather than their parents. They considered using medicine (e.g., sleeping pills and ADHD medication) as coping strategies for sleep and attention problems., Competing Interests: J-MK was employed by VAIV company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Do, Kim, Lim, Kim, Kwon, Kim, Lee and Kim.)

Background: Mindfulness-based training programs have consistently shown efficacy in stress reduction. However, questions regarding the optimal duration and most effective delivery methods remain., Objective: This research explores a 4-week neurofeedback-assisted mindfulness training for employees via a mobile app. The study's core query is whether incorporating neurofeedback can amplify the benefits on stress reduction and related metrics compared with conventional mindfulness training., Methods: A total of 92 full-time employees were randomized into 3 groups: group 1 received mobile mindfulness training with neurofeedback assistance (n=29, mean age 39.72 years); group 2 received mobile mindfulness training without neurofeedback (n=32, mean age 37.66 years); and group 3 were given self-learning paper materials on stress management during their first visit (n=31, mean age 38.65 years). The primary outcomes were perceived stress and resilience scales. The secondary outcomes were mindfulness awareness, emotional labor, occupational stress, insomnia, and depression. Heart rate variability and electroencephalography were measured for physiological outcomes. These measurements were collected at 3 different times, namely, at baseline, immediately after training, and at a 4-week follow-up. The generalized estimating equation model was used for data analysis., Results: The 4-week program showed significant stress reduction (Wald χ 2 2 =107.167, P<.001) and improvements in psychological indices including resilience, emotional labor, insomnia, and depression. A significant interaction was observed in resilience (time × group, Wald χ 4 2 =10.846, P=.02). The post hoc analysis showed a statistically significant difference between groups 1 (least squares mean [LSM] 21.62, SE 0.55) and 3 (LSM 19.90, SE 0.61) at the posttraining assessment (P=.008). Group 1 showed a significant improvement (P<.001) at the posttraining assessment, with continued improvements through the 1-month follow-up assessment period (LSM 21.55, SE 0.61). Physiological indices were analyzed only for data of 67 participants (22 in group 1, 22 in group 2, and 23 in group 3) due to the data quality. The relaxation index (ratio of alpha to high beta power) from the right electroencephalography channel showed a significant interaction (time × group, Wald χ 2 2 =6.947, P=.03), with group 1 revealing the highest improvement (LSM 0.43, SE 0.15) compared with groups 2 (LSM -0.11, SE 0.10) and 3 (LSM 0.12, SE 0.10) at the 1-month follow-up assessment., Conclusions: The study demonstrated that the neurofeedback-assisted group achieved superior outcomes in resilience and relaxation during the 4-week mobile mindfulness program. Further research with larger samples and long-term follow-up is warranted., Trial Registration: ClinicalTrials.gov NCT03787407; https://clinicaltrials.gov/ct2/show/NCT03787407., (©Beomjun Min, Heyeon Park, Johanna Inhyang Kim, Sungmin Lee, Soyoung Back, Eunhwa Lee, Sohee Oh, Je-Yeon Yun, Bung-Nyun Kim, Yonghoon Kim, JungHyun Hwang, Sanghyop Lee, Jeong-Hyun Kim. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 03.10.2023.)

Concerns over the spread of non-native species in aquatic environments have led to the need for effective methods to prevent and control their spread while protecting native species. This study investigated the potential of yeast vacuolar enzymes as a natural hatching inhibitor for controlling aquatic organisms. Hatching experiments with Daphnia magna eggs demonstrated that exposure to yeast vacuole enzymes inhibited hatching in a concentration-dependent manner, suggesting their potential as an effective inhibitor of egg hatching in aquatic organisms. Interestingly, the protease used for comparative purposes did not inhibit hatching, but instead increased the mortality of hatched D. magna. Additionally, chorionic changes were observed in non-hatched D. magna eggs and zebrafish eggs exposed to yeast vacuole enzymes, suggesting that the enzyme can alter the chorion and interfere with hatching. These findings suggest that yeast vacuolar enzymes may be a promising and natural management tool for controlling the spread of harmful aquatic organisms, and further research is warranted to explore their potential for species-specific control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: This study aimed to assess the status of the Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) and propose measures for its growth and development., Methods: The study was conducted using a questionnaire survey targeting members of the Korean Academy of Child and Adolescent Psychiatry. The six key elements analyzed were Access to the journal, Convenience following conversion to English, Recognition as an international journal and institutional achievements, Author perspectives on manuscript submission,Transition to an online-only journal, and Content and identity of the journal., Results: The survey revealed that email notification was highly effective for Journal Accessibility, with the website and search engines also frequently being used by members. Conversion to English in 2018 initially impacted readability and submission rates, but these concerns have decreased over time. However, the Recognition of JKACAP as an international academic journal was still not on par with SCIE journals, highlighting the need for further efforts towards SCIE inclusion. Despite these challenges and limited research opportunities, there was an active intention among members to submit manuscripts. Respondents showed a notable preference for the Transition to an online-only journal. Regarding content and identity of the JKACAP, members predominantly favored review articles and perceived the journal as a research and communication platform for Korean child and adolescent psychiatrists., Conclusion: The results indicate the need for JKACAP to enhance its digital accessibility, provide more support for domestic and international authors, and actively seek SCIE indexing. Addressing the varied content preferences of its members, improving the submission process, and transitioning to an online-only format could further its growth and solidify its position as an internationally recognized academic journal in the field of child and adolescent psychiatry., Competing Interests: Conflicts of Interest The editorial board of JKACAP was not involved in the editorial evaluation or decision to publish this article., (Copyright © 2023 Korean Academy of Child and Adolescent Psychiatry.)

Background: The World Health Organization (WHO) proposed a global action plan for dementia and aimed to have 75% of their member states formulating National Dementia Plans (NDPs) by 2025. The Organization for Economic Cooperation and Development (OECD) proposed the ten key objectives of dementia policy in 2015. Among previous studies on NDPs, few studies have investigated measures for proper implementation of NDPs. This study aimed to compare the implementation basis and specific action plans of NDPs between the G7 countries and South Korea., Methods: We investigated the measures for proper implementation of the NDPs of G7 countries and South Korea. To compare the specific policy approaches, the seven action areas of the WHO action plan and the ten key objectives of dementia policy proposed by the OECD were integrated into 11 targets (prevention, diagnosis, awareness, caregiver support, appropriate environments, long-term care, health service, end-of-life care, care coordination, research and technology, information systems)., Results: Although most NDPs included specific action plans of the 11 targets, caregiver support, safe environments, healthcare services, and end-of-life care were lacking in some NDPs. For implementation, some countries reinforced the policy priority of their NDPs by timely updates, evaluation, legislations, or head-of-state leadership. However, only three countries had a legislative basis, and three countries included outcome measures in their latest NDP., Conclusion: Effective measures for feasible implementation are needed. The WHO should promote not only the establishment of NDPs, but also their proper implementation., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

There is evidence that exposure to perfluoroalkyl substances (PFAS) is associated with attention-deficit/hyperactivity disorder (ADHD) symptoms. Previous studies have focused on prenatal exposure to PFAS, and only few studies have examined the associations of early-childhood exposure, especially at low exposure levels. This study explored the association between early-childhood exposure to PFAS and ADHD symptoms later in childhood. In 521 children, we measured the serum levels of six PFAS in peripheral blood at the ages of 2 and 4 years, including perfluorooctanoate (PFOA), perfluornonanoicacid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). The ADHD Rating Scale IV (ARS) was utilized to measure ADHD traits at 8 years of age. We explored the relationship between PFAS and ARS scores using Poisson regression models after adjusting for potential confounders. Levels of exposure to individual PFAS and the summed value were divided into quartiles to examine possible nonlinear relationships. All six PFAS exhibited inverted U-shaped curves. Children in the 2nd and 3rd quartile levels of each PFAS showed higher ARS scores than those in the1 st quartile level. Below the 3rd quartile of the summed levels of six PFAS (ΣPFAS), a doubling of the ΣPFAS was associated with an 20.0 % (95 % CI: 9.5 %, 31.5 %) increase in ADHD scores. However, at the age of 4 years, none of the evaluated PFAS exhibited linear or nonlinear associations with the ARS scores. Thus, school-aged children may be vulnerable to the neurotoxic effects of exposure to PFAS at age 2 that contribute to ADHD, particularly at low to mid-levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have inappropriately influenced the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the study of the brain, large and high-density microelectrode arrays have been widely used to study the behavior of neurotransmission. CMOS technology has facilitated these devices by enabling the integration of high-performance amplifiers directly on-chip. Usually, these large arrays measure only the voltage spikes resulting from action potentials traveling along firing neuronal cells. However, at synapses, communication between neurons occurs by the release of neurotransmitters, which cannot be measured on typical CMOS electrophysiology devices. Development of electrochemical amplifiers has resulted in the measurement of neurotransmitter exocytosis down to the level of a single vesicle. To effectively monitor the complete picture of neurotransmission, measurement of both action potentials and neurotransmitter activity is needed. Current efforts have not resulted in a device that is capable of the simultaneous measurement of action potential and neurotransmitter release at the same spatiotemporal resolution needed for a comprehensive study of neurotransmission. In this paper, we present a true dual-mode CMOS device that fully integrates 256-ch electrophysiology amplifiers and 256-ch electrochemical amplifiers, along with an on-chip 512 electrode microelectrode array capable of simultaneous measurement from all 512 channels.

Spatial repellents are emerging as a promising approach to reduce vector-disease burden; however, the evolution of genetically resistant mosquitoes decreases repellent efficacy. The development of flight chambers to investigate spatial repellent application techniques is vital for sustainable mosquito control. We present an air-dilution chamber as a novel bioassay to study mosquito flight behavior responses to chemical gradients of the volatile, pyrethroid transfluthrin (TF). Air dilution was used to simulate a larger environment of stable concentration gradients verified with carbon dioxide (CO2) which was homogenously delivered and measured across the chamber to achieve a 5× inlet/outlet [CO2] ratio with 0.17 m/s outlet velocity. Female Aedes (Ae.) aegypti (Diptera: Culicidae, Linnaeus, 1762) were exposed to volatilized TF paired with heat, CO2, and Biogents-Sweetscent host-cues. Tandem solvent extraction-gas chromatography-mass spectrometry (SE-GC-MS) was used to quantify air samples taken during TF emanations with a limit of detection (LOD) and quantification (LOQ) of 2 ± 1 and 5 ± 2 parts-per-trillion (ppt) TF, respectively. Homogenous air diluted emanation of the spatial repellent TF was at least twice that of the 5× CO2 gradient with the same air flow in the chamber. The airborne TF concentrations the mosquitoes were exposed to range from 1 to 170 ppt. Video recordings of mosquito behavior during host-cues exposure revealed increased inlet activity, while exposure to TF protected host resulted in decreased inlet activity over time with inlet-outlet mosquito positional variation. This novel flight chamber design can simulate 'long'-range exposure with simultaneous quantitation of airborne spatial repellent to understand dose-dependent effects on mosquito behavior., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The prolonged coronavirus disease-2019 (COVID-19) pandemic is likely to cause psychological distress in people. This systematic review aimed to identify the effectiveness of virtual reality (VR)-based psychological intervention among individuals with psychological distress during the COVID-19 crisis. PubMed, Ovid MEDLINE, Cochrane Library, Web of Science, Embase, and PsycINFO databases were searched for articles published until July 2022., Methods: The available citations were deduplicated and screened by two authors using the title and abstract information. Eligibility criteria were constructed according to the PICOT guidelines. Empirical studies of all designs and comparator groups were included if they appraised the impact of an immersive VR intervention on any standardized measure indicative of psychological distress (stress, anxiety, depression, and post-traumatic symptoms) or improvements in quality of life in participants, including COVID-19 patients, medical staff working with COVID-19 patients, and people who had experienced strict social distancing during the COVID-19 pandemic., Results: The results were discussed using a narrative synthesis because of the heterogeneity between studies. Seven of the studies met the inclusion criteria. There were two randomized controlled trials and five uncontrolled studies on VR interventions., Conclusion: All studies reported significant improvement in a wide range of psychological distress during COVID-19, ranging from stress, anxiety, depression, and post-traumatic symptoms to quality of life, supporting the efficacy of VR-based psychological intervention. Our results suggest that VR intervention has potential to ameliorate COVID-19-related psychological distress with efficacy and safety.

Importance: Postnatal growth may be associated with longitudinal brain development in children born preterm., Objective: To compare brain microstructure and functional connectivity strength with cognitive outcomes in association with postnatal growth among early school-aged children born preterm with extremely low birth weight., Design, Setting, and Participants: This single-center cohort study prospectively enrolled 38 children 6 to 8 years of age born preterm with extremely low birth weight: 21 with postnatal growth failure (PGF) and 17 without PGF. Children were enrolled, past records were retrospectively reviewed, and imaging data and cognitive assessments occurred from April 29, 2013, through February 14, 2017. Image processing and statistical analyses were conducted through November 2021., Exposure: Postnatal growth failure in the early neonatal period., Main Outcomes and Measures: Diffusion tensor images and resting-state functional magnetic resonance images were analyzed. Cognitive skills were tested using the Wechsler Intelligence Scale; executive function was assessed based on a composite score calculated from the synthetic composite of the Children's Color Trails Test, STROOP Color and Word Test, and Wisconsin Card Sorting Test; attention function was evaluated using the Advanced Test of Attention (ATA); and the Hollingshead Four Factor Index of Social Status-Child was estimated., Results: Twenty-one children born preterm with PGF (14 girls [66.7%]), 17 children born preterm without PGF (6 girls [35.3%]), and 44 children born full term (24 girls [54.5%]) were recruited. Attention function was less favorable in children with PGF than those without PGF (mean [SD] ATA score: children with PGF, 63.5 [9.4]; children without PGF, 55.7 [8.0]; P = .008). Significantly lower mean (SD) fractional anisotropy in the forceps major of the corpus callosum (0.498 [0.067] vs 0.558 [0.044] vs 0.570 [0.038]) and higher mean (SD) mean diffusivity in the left superior longitudinal fasciculus-parietal bundle (8.312 [0.318] vs 7.902 [0.455] vs 8.083 [0.393]; originally calculated as millimeter squared per second and rescaled 10 000 times as mean diffusivity × 10 000) were seen among children with PGF compared with children without PGF and controls, respectively. Decreased resting-state functional connectivity strength was observed in the children with PGF. The mean diffusivity of the forceps major of the corpus callosum significantly correlated with the attention measures (r = 0.225; P = .047). Functional connectivity strength between the left superior lateral occipital cortex and both superior parietal lobules correlated with cognitive outcomes of intelligence (right superior parietal lobule, r = 0.262; P = .02; and left superior parietal lobule, r = 0.286; P = .01) and executive function (right superior parietal lobule, r = 0.367; P = .002; and left superior parietal lobule, r = 0.324; P = .007). The ATA score was positively correlated with functional connectivity strength between the precuneus and anterior division of the cingulate gyrus (r = 0.225; P = .048); however, it was negatively correlated with functional connectivity strength between the posterior cingulate gyrus and both superior parietal lobules (the right superior parietal lobule [r = -0.269; P = .02] and the left superior parietal lobule [r = -0.338; P = .002])., Conclusions and Relevance: This cohort study suggests that the forceps major of the corpus callosum and the superior parietal lobule were vulnerable regions in preterm infants. Preterm birth and suboptimal postnatal growth could have negative associations with brain maturation, including altered microstructure and functional connectivity. Postnatal growth may be associated with differences in long-term neurodevelopment among children born preterm.

Objective: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus., Methods: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures., Results: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30-60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation., Conclusion: These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO 2 ) is scarce. Herein, we investigate the associations between prenatal SO 2 exposure and ADHD rating scale (ARS) at ages 4, 6 and 8 years repeatedly in a mother-child cohort (n = 329). Whole blood samples were obtained at ages 2 and 6 years, and genome-wide DNA methylation (DNAm) was analyzed for 51 children using the Illumina Infinium HumanMethylation BeadChip. We analyzed the associations between prenatal SO 2 exposure and DNAm levels at ages 2 and 6, and further investigated the association between the DNAm and ARS at ages 4, 6 and 8. Prenatal SO 2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO 2 exposure levels. Of the 6 CpGs, cg07583420 (INS-IGF2) was persistently linked with ARS at ages 4, 6 and 8. Epigenome-wide analysis showed that DNAm at 6733 CpG sites were associated with prenatal SO 2 exposure, of which 58 CpGs involved in Notch signalling pathway were further associated with ARS at age 4, 6 and 8 years, persistently. DNAm at age 6 was not associated with prenatal SO 2 exposure. Changes in DNAm levels associated with prenatal SO 2 exposure during early childhood are associated with increases in ARS in later childhood., (© 2023. The Author(s).)

There are three presentations of attention-deficit/hyperactivity disorder (ADHD): the predominantly inattention (ADHD-PI), predominantly hyperactive-impulsive (ADHD-HI), and combined (ADHD-C) presentations of ADHD. These may represent distinct childhood-onset neurobehavioral disorders with separate etiologies. ADHD diagnoses are behaviorally based, so investigations into potential etiologies should be founded on behavior. Animal models of ADHD demonstrate face, predictive, and construct validity when they accurately reproduce elements of the symptoms, etiology, biochemistry, and disorder treatment. Spontaneously hypertensive rats (SHR/NCrl) fulfill many validation criteria and compare well with clinical cases of ADHD-C. Compounding the difficulty of selecting an ideal model to study specific presentations of ADHD is a simple fact that our knowledge regarding ADHD neurobiology is insufficient. Accordingly, the current review has explored a potential animal model for a specific presentation, ADHD-PI, with acceptable face, predictive, and construct validity. The Thrsp gene could be a biomarker for ADHD-PI presentation, and THRSP OE mice could represent an animal model for studying this distinct ADHD presentation.

Background: Adequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea., Methods: A total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient (< 100 μg/L), adequate (100-199 μg/L), more than adequate (200-299 μg/L), mild excessive (300-999 μg/L), and severe excessive (≥ 1000 μg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated., Results: The median TSH level was 2.3 μIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 μg/L, with higher levels in boys (684 μg/L vs. 545 μg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (β = - 0.04, p = 0.032 for mild excess; β = - 0.04, p = 0.042 for severe excess) and T3 levels (β = - 8.12, p = 0.009 for mild excess; β = - 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (β = 0.04, p = 0.046)., Conclusion: Excess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Cho, Lim, Kim, Kim, Hong, Park, Shin and Lee.)

Background and Aims: Online gaming motives have proven to be useful in differentiating problematic engagement in online gaming. However, the mixture modeling approach for classifying problematic subtypes based on gaming motives remains limited. This study attempted to differentiate heterogeneous online gamers into more homogenous subtypes based on gaming motives using latent profile analysis (LPA). We also compared various psychological and gaming/leisure related variables across the derived profiles., Methods: A total of 674 Korean online game users (mean age = 21.81 years, male = 76%) completed self-report questionnaires, including the Korean version of the Motives for Online Gaming Questionnaire (K-MOGQ). After the LPA, the relationships between latent profile membership and auxiliary variables were explored., Results: Four latent profiles were identified, that were further classified into one problematic (highly motivated-dissatisfied gamer), one highly engaged (highly motivated-satisfied gamer), and two casual (moderately-motivated casual gamer and lowly-motivated casual gamer) gamer profiles. Inter-profile comparisons revealed that highly motivated-dissatisfied gamer had the most pathological profile, characterized by high Internet gaming disorder (IGD) tendency, neuroticism, and impulsivity, but the lowest recreation motive. While highly motivated-satisfied gamer also demonstrated a heightened IGD tendency, they showed positive patterns of psychological and gaming/leisure-related variables, which indicated they could be better considered as high engaged instead of problematic gamers., Discussion and Conclusions: These results indicate that the recreation motive, in addition to fantasy or escape motives, is an important factor in differentiating maladaptive online gamers. Classifying online gamers based on gaming motives can contribute to a clearer conceptualization of heterogeneous gamers, paving the way for individualized assessment and treatment planning.

The majority of the vitamin D that is present in the blood binds to vitamin D binding protein (VDBP) and circulates in the form of a complex (VDBP-Complex). Knowing the level of vitamin D in the body is crucial for vitamin D-related treatments so that the right dosage of vitamin D can be given. In other words, it is essential to distinguish between the protein VDBP and the complex form bound to vitamin D. As a novel way for the detection of VDBP-Complex, a more effective phage display methodology was applied in this study along with the addition of two approaches. In order to screen a sequence specific to the target only, the pre-binding method and after-binding method were performed. VDBP-Complex was directly coated on the petri dishes. In order to select phages that specifically bind to the VDBP-Complex, random phages were attached, and selected by 7 times of biopanning. Individual DNA sequences were analyzed for each biopanning to find specific peptide sequences for VDBP-Complex. The affinity of binding phages was verified by ELISA assay using an anti-M13 antibody. The phage having a sequence of SFTKTSTFTWRD (called as M3) has shown the highest binding affinity to VDBP-Complex. As a result of the removal test of VDBP-Complex using magnetic beads conjugated with M3 peptide, it was confirmed that significant decrease of VDBP-Complex. The unique characteristic of the M3 sequence was confirmed through a sequence-modified peptide (SFT motif). That is, it is expected that the M3 peptide may be used to determine the vitamin D levels in the blood., (© 2023. The Author(s).)

Children with attention-deficit/hyperactivity disorder (ADHD) often struggle with impaired executive function, temporal processing, and visuospatial memory, hallmarks of the predominantly inattentive presentation (ADHD-PI), subserved by the hippocampus. However, the specific genes/proteins involved and how they shape hippocampal structures to influence ADHD behavior remain poorly understood. As an exploratory tool, hippocampal dentate gyri tissues from thyroid hormone-responsive protein overexpressing (THRSP OE) mice with defining characteristics of ADHD-PI were utilized in proteomics. Integrated proteomics and network analysis revealed an altered protein network involved in Wnt signaling. Compared with THRSP knockout (KO) mice, THRSP OE mice showed impaired attention and memory, accompanied by dysregulated Wnt signaling affecting hippocampal dentate gyrus cell proliferation and expression of markers for neural stem cell (NSC) activity. Also, combined exposure to an enriched environment and treadmill exercise could improve behavioral deficits in THRSP OE mice and Wnt signaling and NSC activity. These findings show new markers specific to the ADHD-PI presentation, converging with the ancient and evolutionary Wnt signaling pathways crucial for cell fate determination, migration, polarity, and neural patterning during neurodevelopment. These findings from THRSP OE mice support the role of Wnt signaling in neurological disorders, particularly ADHD-PI presentation., (© 2023. The Author(s).)

Multimodal imaging studies targeting preschoolers and low-functioning autism spectrum disorder (ASD) patients are scarce. We applied machine learning classifiers to parameters from T1-weighted MRI and DTI data of 58 children with ASD (age 3-6 years) and 48 typically developing controls (TDC). Classification performance reached an accuracy, sensitivity, and specificity of 88.8%, 93.0%, and 83.8%, respectively. The most prominent features were the cortical thickness of the right inferior occipital gyrus, mean diffusivity of the middle cerebellar peduncle, and nodal efficiency of the left posterior cingulate gyrus. Machine learning-based analysis of MRI data was useful in distinguishing low-functioning ASD preschoolers from TDCs. Combination of T1 and DTI improved classification accuracy about 10%, and large-scale multi-modal MRI studies are warranted for external validation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Tic disorders are highly heritable; however, growing evidence suggests that environmental factors play a significant role in their pathogenesis. Studies on these factors have been inconsistent, with conflicting results. Therefore, this study aimed to examine the associations of pre- and perinatal exposure to Tourette syndrome (TS) or chronic tic disorders (CTD) in Korean school-aged children., Methods: This case-control study used data from a large prospective cohort study. The primary outcome was TS/CTD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version. Demographic, pre-, and perinatal information was obtained from the maternal questionnaires. Data between the TS/CTD and control groups were compared using the chi-squared or Student's t-test, as appropriate. Two-step logistic regression analyses were used to test the association between TS/CTD and pre- and perinatal risk factors., Results: We included of 223 children (78 with TS/CTD and 145 controls). Significant differences in the demographic data between the two groups were observed. The male sex ratio, mean parental age, parental final education level, and family history of tics were included as confounders. In the final adjusted multivariable model, TS/CTD was significantly associated with antiemetic exposure during pregnancy (odds ratio [OR]=16.61, 95% confidence interval [CI] 1.49-185.22, p=0.02) and medically assisted reproduction (OR=7.89, 95% CI 2.28-27.28, p=0.01)., Conclusion: Antiemetic exposure and medically assisted reproduction are significantly associated with the risk of TS/CTD. These results should be replicated in future prospective and gene-by-environment studies., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Academy of Child and Adolescent Psychiatry.)

The vacuoles of the yeast Saccharomyces cerevisiae are closely related to mammalian lysosomes and play a role in macromolecular degradation due to the hydrolytic enzymes present inside. The vacuoles also regulate osmotic pressure and control cellular homeostasis. In previous results, vacuoles were shown to activate the immune response of macrophages by promoting the production of immune-mediated transporters nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokines. In this study, the effects of vacuoles on the phagocytosis activity of RAW264.7 cells and their potential as immune enhancers were evaluated, and receptors capable of recognizing vacuoles were examined. An investigation using the phagocytes assay showed that phagocytosis activity increased by the vacuole. Besides, after treatment with TLR2/4 inhibitor, the expression of pro-inflammatory cytokines by vacuoles was significantly reduced and the inducible nitric oxide synthase (iNOS) protein was also significantly reduced. However, treatment with a TLR2 inhibitor did not reduce the production of interleukin-6 (IL)-6, a pro-inflammatory cytokine. As a result of confirming the activation of TLR2/4 using Western blot and immunofluorescence (IF), the TLR2/4 protein expression and fluorescence intensity increased depending on the concentration of vacuoles. Yeast vacuoles significantly upregulate protein expression of p-p65/p-p38 MAPKs. In summary, the vacuoles isolated from S. cerevisiae in macrophages have increased phagocytic ability at a concentration of 20 (µg/ml) and can function as immune-enhancing agent suggesting that TLR2/4 mediated the p38 MAPK/nuclear factor kappa B signaling pathway., (© 2022 Wiley Periodicals LLC.)