Prenatal and early-life air pollutant exposure and epigenetic aging acceleration.

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 (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) 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 PM2.5 (4.56 µg/m3) 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 PM2.5 (4.76 µg/m3) 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). PM10 (4.30 µg/m3) and O3 (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.

Patterns of comorbid PTSD, depression, alcohol use disorder, and insomnia symptoms in firefighters: A latent profile analysis.

BACKGROUND: Firefighters are an at-risk population for multiple psychiatric conditions, including posttraumatic stress disorder (PTSD), depression, alcohol use disorders (AUDs), and insomnia. These disorders are likely to co-occur; however, patterns of comorbidity have scarcely been investigated in firefighters. We aimed to identify subgroups of comorbidity of PTSD, depression, AUDs, and insomnia in a nationwide population of firefighters in South Korea. METHODS: A total of 54,054 firefighters responded to an online survey. Latent classes of comorbidity were categorized using latent profile analysis (LPA) based on the symptom scores of PTSD, depression, AUDs, and insomnia. Analysis of variance was performed to compare the characteristics of the identified classes, and multinomial logistic regression was conducted to examine whether anger reactions, resilience, and number of traumatic events predicted class membership. RESULTS: The LPA identified four subgroups: minimal symptoms (n = 42,948, 79.5 %), predominant PTSD (n = 2858, 5.3 %), subthreshold symptoms and comorbidity (n = 7003, 13.0 %), and high symptoms and comorbidity (n = 1245, 2.3 %). Three comorbidity classes were defined based on severity and one class showed predominant PTSD symptoms. Number of traumatic exposures predicted predominant PTSD, while resilience and anger reactions predicted severity of comorbidities. LIMITATIONS: The cross-sectional design and usage of self-reported questionnaires are limitations of this study. CONCLUSIONS: The severity of PTSD, depression, AUDs and insomnia tend to correlate and co-occur in firefighters. Our findings highlight the need to assess comorbid symptoms in firefighters and need to reduce anger reactions and enhance resilience in those with multiple comorbidities.

Relationship of bisphenol A substitutes bisphenol F and bisphenol S with adiponectin/leptin ratio among children from the environment and development of children cohort.

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 (ß = 0.160, P= 0.044), higher fat mass (ß = 0.104, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 0.428, P< 0.001) compared with the non-detected group. The urinary BPF-detected group had a higher fat mass (ß = 0.074, P< 0.001), lower adiponectin concentration (ß =- 0.069, P< 0.001), higher leptin concentration (ß = 0.360, P< 0.001), and lower A/L ratio (ß =- 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.

Diagnosis and Assessment of Autism Spectrum Disorder in South Korea.

Autism spectrum disorder (ASD) is diagnosed by the clinical decision of a trained professional based on the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition or International Classification of Diseases 11th Revision diagnostic criteria. To obtain information for diagnostic formulation, professionals should explore detailed developmental history, and can use structured or semi-structured assessment tools to observe interaction between the child and parents or strangers. Diagnostic assessment should include a profile of the strength and weaknesses of the individual and should be conducted using an optimal approach by a multidisciplinary team with appropriate techniques and experience. Assessment of language, cognitive, neuropsychological, and adaptive functioning should be conducted in ASD individuals prior to establishing an individualized treatment plan. Genetic testing, brain magnetic resonance imaging or electroencephalogram testing can be considered for identification of underlying causes.

Effects of iodine status on thyroid volume and goiter in children living in an iodine-replete area.

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.

The Effectiveness of a Neurofeedback-Assisted Mindfulness Training Program Using a Mobile App on Stress Reduction in Employees: Randomized Controlled Trial.

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 χ22=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 χ42=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 χ22=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.

Classifying Children with ADHD Based on Prefrontal Functional Near-infrared Spectroscopy Using Machine Learning.

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.

Rhythm-based assessment and training for children with attention deficit hyperactivity disorder (ADHD): a feasibility study protocol.

Background: The timing-related deficits in individuals with attention deficit hyperactivity disorder (ADHD) contribute to the symptom-related difficulties and cognitive impairments. Current assessment and training measurement only target specific aspects of the timing ability, highlighting the need for more advanced tools to address timing deficits in ADHD. The aim of this study is to develop and validate a rhythm-based assessment and training (RAT) program, which intends to provide a comprehensive understanding of and enhancement to the time-related abilities of children with ADHD, thereby demonstrating its clinical efficacy. Methods: We will use randomized crossover trials in this study, with participants being randomly assigned to either start with the RAT and then proceed to cognitive training or start with cognitive training and then proceed to the RAT. Both groups will undergo pre- and post- evaluations. The evaluation will be administered immediately before and after the 4-week training period using diagnostic questionnaires, cognitive evaluation tools, and resting electroencephalography (EEG) measurements. Notably, EEG measurements will be conducted concurrently with the RAT evaluations. Discussion: This study develops and evaluates the feasibility and effectiveness of a RAT while using EEG measurements to elucidate the underlying therapeutic mechanism of auditory rhythm at varying levels of complexity. The study will investigate the potential of RAT as a supplementary or alternative approach for managing ADHD. The multifaceted data collected will yield valuable insights to customize training agendas based on individual developmental stages and prognoses.

Psychobiotics and fecal microbial transplantation for autism and attention-deficit/hyperactivity disorder: microbiome modulation and therapeutic mechanisms.

Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).

Nonsuicidal Self-Injury and Its Mediation Effect on the Association Between Posttraumatic Stress Disorder, Depression, and Suicidal Behavior in Firefighters.

OBJECTIVE: This study aimed to investigate the prevalence, clinical characteristics, and the correlates of nonsuicidal self-injury (NSSI) in firefighters. We also investigated the mediating role of NSSI frequency in the association between posttraumatic stress disorder (PTSD), depression, and suicidal behavior. METHODS: A total of 51,505 Korean firefighters completed a web-based self-reported survey, including demographic and occupational characteristics, NSSI, PTSD, depression, and suicidal behavior. Multivariable logistic regression analyses and serial mediation analyses were performed. RESULTS: The 1-year prevalence of NSSI was 4.67% in Korean firefighters. Female gender, the presence of recent traumatic experience, and PTSD and depression symptoms were correlated with NSSI. Serial mediation analyses revealed that NSSI frequency mediated the association between PTSD, depression, and suicidal behavior; it indicates more severe PTSD was sequentially associated with more severe depression symptoms and more frequent NSSI, leading to higher risk of suicidal behavior. CONCLUSION: NSSI is prevalent and may play a significant mediating role when PTSD is associated with suicidal behavior in firefighters. Our results imply the need for screening and early intervention of NSSI in firefighters.

DNA methylation is associated with prenatal exposure to sulfur dioxide and childhood attention-deficit hyperactivity disorder symptoms.

Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO2) is scarce. Herein, we investigate the associations between prenatal SO2 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 SO2 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 SO2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO2 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 SO2 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 SO2 exposure. Changes in DNAm levels associated with prenatal SO2 exposure during early childhood are associated with increases in ARS in later childhood.

Relationship of iodine excess with thyroid function in 6-year-old children living in an iodine-replete area.

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 (ß = - 0.04, p = 0.032 for mild excess; ß = - 0.04, p = 0.042 for severe excess) and T3 levels (ß = - 8.12, p = 0.009 for mild excess; ß = - 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 (ß = 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.

Association between early-childhood exposure to perfluoroalkyl substances and ADHD symptoms: A prospective cohort study.

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 the1st 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.

Classification of Preschoolers with Low-Functioning Autism Spectrum Disorder Using Multimodal MRI Data.

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.

The mediating role of the gut microbiome in the association between ambient air pollution and autistic traits.

Air pollution has been reported to be an environmental risk factor for autism spectrum disorder. However, the gut microbiome's role as a potential mediator has not been investigated. We aimed to clarify whether particulate matter with an aerodynamic diameter ≤10 µm (PM10) and nitrogen dioxide (NO2) exposure impact autistic traits through the gut microbiome. Using 170 mother-child pairs, PM10 and NO2 exposure levels during pregnancy (1st, 2nd, and 3rd trimesters) and annual residential PM10 levels at age 2, 4, and 6 years were estimated. Autistic traits and gut microbiome were assessed at age 6 years. The associations of PM10 or NO2 exposure, gut microbiome composition, and autistic traits were explored, and mediation analyses of statistically significant findings were also conducted. Exposure to PM10 during the 1st trimester of pregnancy was associated with increased autistic traits (10.6% change per interquartile range (IQR) increase, 95% confidence interval [CI]: 1.1, 21.0) and with Proteobacteria relative abundance at age 6 years (66.9% change per IQR increase, 95% CI: 21.3, 129.8). First trimester NO2 exposure was associated with autistic traits (12.1% change, 95% CI: 0.1, 25.5) and Proteobacteria relative abundance at age 6 years (48.1% change, 95% CI: -0.1, 119.6). Proteobacteria relative abundance was related to autistic traits (4.4% change per 2-fold increase, 95% CI: 1.3, 7.5). Relations between PM10 or NO2 exposure during the 1st trimester and autistic traits at age 6 years were partially mediated by Proteobacteria (proportion mediated 23.2%, p = 0.01 and 16.7%, p = 0.06; respectively). PM10 and possibly NO2 exposure during early pregnancy may affect autistic traits at age 6 years through the alteration of Proteobacteria abundance.

Effects of Chronic Diseases on All-Cause Mortality in People with Mental Illness: A Retrospective Cohort Study Using the Korean National Health Insurance Service-Health Screening.

The aim of this study was to compare mortality and the prevalence of chronic diseases between people with mental illness and the general population, and to explore which chronic diseases increase the risk of all-cause mortality, especially in people with mental illness. This study assessed data from the 2002-2019 Korean National Health Insurance Service-Health Screening sample cohort. Results revealed that all-cause mortality was higher in people with mental illness compared to people without mental illness (11.40% vs. 10.28%, p = 0.0022). Several chronic diseases have a higher prevalence and risk of all-cause mortality in individuals with mental illness than the general population. Among people with the same chronic disease, those with mental disorders had a higher risk of all-cause mortality. Cancer (aHR 2.55, 95% CI 2.488-2.614), liver cirrhosis (aHR 2.198, 95% CI 2.086-2.316), and arrhythmia (aHR 1.427, 95% CI 1.383-1.472) were the top three chronic diseases that increased the risk of all-cause mortality in people with mental illness compared to people without mental illness. Our results suggest the need for more attention to chronic diseases for people with mental illness in clinical practice by explaining the effect of chronic disease on all-cause mortality in people with mental illness.

Sparse Hierarchical Representation Learning on Functional Brain Networks for Prediction of Autism Severity Levels.

Machine learning algorithms have been widely applied in diagnostic tools for autism spectrum disorder (ASD), revealing an altered brain connectivity. However, little is known about whether an magnetic resonance imaging (MRI)-based brain network is related to the severity of ASD symptoms in a large-scale cohort. We propose a graph convolution neural network-based framework that can generate sparse hierarchical graph representations for functional brain connectivity. Instead of assigning initial features for each node, we utilized a feature extractor to derive node features and the extracted representations can be fed to a hierarchical graph self-attention framework to effectively represent the entire graph. By incorporating connectivity embeddings in the feature extractor, we propose adjacency embedding networks to characterize the heterogeneous representations of the brain connectivity. Our proposed model variants outperform the benchmarking model with different configurations of adjacency embedding networks and types of functional connectivity matrices. Using this approach with the best configuration (SHEN atlas for node definition, Tikhonov correlation for connectivity estimation, and identity-adjacency embedding), we were able to predict individual ASD severity levels with a meaningful accuracy: the mean absolute error (MAE) and correlation between predicted and observed ASD severity scores resulted in 0.96, and r = 0.61 (P < 0.0001), respectively. To obtain a better understanding on how to generate better representations, we investigate the relationships between the extracted feature embeddings and the graph theory-based nodal measurements using canonical correlation analysis. Finally, we visualized the model to identify the most contributive functional connections for predicting ASD severity scores.

Altered Cerebral Curvature in Preterm Infants Is Associated with the Common Genetic Variation Related to Autism Spectrum Disorder and Lipid Metabolism.

Preterm births are often associated with neurodevelopmental impairment. In the critical developmental period of the fetal brain, preterm birth disrupts cortical maturation. Notably, preterm birth leads to alterations in the fronto-striatal and temporal lobes and the limbic region. Recent advances in MRI acquisition and analysis methods have revealed an integrated approach to the genetic influence on brain structure. Based on imaging studies, we hypothesized that the altered cortical structure observed after preterm birth is associated with common genetic variations. We found that the presence of the minor allele at rs1042778 in OXTR was associated with reduced curvature in the right medial orbitofrontal gyrus (p < 0.001). The presence of the minor allele at rs174576 in FADS2 (p < 0.001) or rs740603 in COMT (p < 0.001) was related to reduced curvature in the left posterior cingulate gyrus. This study provides biological insight into altered cortical curvature at term-equivalent age, suggesting that the common genetic variations related to autism spectrum disorder (ASD) and lipid metabolism may mediate vulnerability to early cortical dysmaturation in preterm infants.

Relationship between bisphenol A, bisphenol S, and bisphenol F and serum uric acid concentrations among school-aged children.

BACKGROUND: Hyperuricemia has a suspected relationship with hypertension, metabolic syndrome, kidney disease, and cardiovascular disease. Endocrine disruptors may affect uric acid metabolism; however, few epidemiologic studies have been performed in children regarding newly developed bisphenol A (BPA) substitutes. We evaluated the associations between BPA, bisphenol S (BPS), and bisphenol F (BPF) exposure and serum uric acid concentrations in 6-year-old Korean children. METHODS: From the Environment and Development of Children cohort study, six-year-old children (N = 489; 251 boys) who underwent an examination during 2015-2017 were included. Anthropometry, questionnaires, and biological samples were evaluated. BPA, BPS, and BPF levels were measured from spot urine samples, and log-transformed or categorized into groups for analysis. We constructed linear regression models adjusting for age, sex, urinary creatinine levels, body mass index z-scores, and estimated glomerular filtration rates. RESULTS: Mean serum uric level was 4.2 mg dL-1 (0.8 SD) without sex-differences. Among the three bisphenols, higher BPS exposure was associated with increased serum uric acid concentrations (P-value for trend = 0.002). When BPS levels were categorized into three groups (non-detection < 0.02 µg L-1 vs. medium BPS; 0.02-0.05 µg L-1 vs. high BPS ≥ 0.05 µg L-1), the high BPS group showed higher serum uric acid concentrations (by 0.26 mg dL-1, P = 0.003) than the non-detection group after adjusting for covariates, which was significant in boys but not girls. DISCUSSIONS: Urinary BPS levels was positively associated with serum uric acid concentrations in 6-year-old children, and the association was more pronounced in boys. Considering the increasing use of BPS and concerning effect of hyperuricemia on health outcomes, their positive relationship should be investigated further.

Impact of Preterm Birth on Neurodevelopmental Disorders in South Korea: A Nationwide Population-Based Study.

Neurodevelopmental disorder (NDD) in preterm infants has become of great interest. We aimed to investigate the impact of preterm birth on the proportion of NDD using nationwide data provided by the Korean National Health Insurance Service. We included 4894 extremely preterm or extremely low-birth-weight (EP/ELBW; <28 weeks of gestation or birth weight < 1000 g) infants, 70,583 other preterm or low-birth-weight (OP/LBW; 28−36 weeks of gestation or birth weight < 2500 g) infants, and 264,057 full-term infants born between 2008 and 2015. We observed their neurodevelopment until 6 years of age or until the year 2019, whichever occurred first. Diagnoses of NDDs were based on the World Health Organization's International Classification of Diseases 10th revision. An association between preterm birth and NDD was assessed using a multivariable logistic regression model. There was a stepwise increase in the risk of overall NDD with increasing degree of prematurity, from OP/LBW (adjusted odds ratio 4.46; 95% confidence interval 4.34−4.58), to EP/ELBW (16.15; 15.21−17.15). The EP/ELBW group was strongly associated with developmental delay (21.47; 20.05−22.99), cerebral palsy (88.11; 79.89−97.19), and autism spectrum disorder (11.64; 10.37−13.06). Preterm birth considerably increased the risk of NDD by the degree of prematurity.