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Abstract 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.

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.

Abstract The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP;

Studies of social dysfunction in patients with autism spectrum disorder (ASD) have generally focused on the perception of emotional words and facial affect. Brain imaging studies have suggested that the fusiform gyrus is associated with both the comprehension of language and face recognition. We hypothesized that patients with ASD would have decreased ability to recognize affect via emotional words and facial emoticons, relative to healthy comparison subjects. In addition, we expected that this decreased ability would be associated with altered activity of the fusiform gyrus in patients with ASD. Ten male adolescents with ASDs and ten age and sex matched healthy comparison subjects were enrolled in this case-control study. The diagnosis of autism was further evaluated with the Autism Diagnostic Observation Schedule. Brain activity was assessed using functional magnetic resonance imaging (fMRI) in response to emotional words and facial emoticon presentation. Sixty emotional words (45 pleasant words +15 unpleasant words) were extracted from a report on Korean emotional terms and their underlying dimensions. Sixty emoticon faces (45 pleasant faces +15 unpleasant faces) were extracted and modified from on-line sites. Relative to healthy comparison subjects, patients with ASD have increased activation of fusiform gyrus in response to emotional aspects of words. In contrast, patients with ASD have decreased activation of fusiform gyrus in response to facial emoticons, relative to healthy comparison subjects. We suggest that patients with ASD are more familiar with word descriptions than facial expression as depictions of emotion.

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 (

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.

Abstract 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.

IntroductionSince 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.MethodsThe 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.ResultsAdolescents 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.ConclusionDuring 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.

BackgroundMindfulness-based training programs have consistently shown efficacy in stress reduction. However, questions regarding the optimal duration and most effective delivery methods remain. ObjectiveThis 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. MethodsA 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. ResultsThe 4-week program showed significant stress reduction (Wald χ22=107.167, P

Proteomics in the hippocampal dentate gyri reveal that behavioural impairments in THRSP-overexpressing mice could be regulated by Wnt signalling.

Abstract While thyroid disturbances during perinatal and postnatal periods in preterm infants with congenital hypothyroidism reportedly disrupt neuronal development, no study has considered the effect of thyroid disturbances in premature infants with subclinical hypothyroidism with elevations of thyroid stimulating hormone. We aimed to identify altered fiber integrity from the thalamus to cortices in preterm infants with subclinical hypothyroidism. All preterm infants born were categorized according to thyroid stimulating hormone levels through serial thyroid function tests (36 preterm controls and 29 preterm infants with subclinical hypothyroidism). Diffusion tensor images were acquired to determine differences in thalamocortical fiber lengths between the groups, and cerebral asymmetries were investigated to observe neurodevelopmental changes. Thalamocortical fiber lengths in the subclinical hypothyroidism group were significantly reduced in the bilateral superior temporal gyrus, heschl’s gyrus, lingual gyrus, and calcarine cortex (all p

BackgroundAdequate 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.MethodsA 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.ResultsThe 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).ConclusionExcess 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.

Custodio et al. characterise a mouse model of ADHD in which thyroid hormone-responsive protein is overexpressed. They demonstrate that reduced levels of striatal triiodothyronine (T3) play a role in inattention and memory impairment in this model and that the model could be used in future studies examining the predominantly inattentive subtype of ADHD.

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.

Objectives Bisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children. Methods Prenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T3, and free T4) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations. Results The associations between prenatal BPA and total T3 levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T4 levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only. Conclusions Our findings identified significant associations between prenatal BPA exposure and total T3 levels in all children and between BPF exposure and free T4 levels in girls only.

Background: Bisphenol A (BPA) has been linked to attention-deficit/hyperactivity disorder (ADHD) symptoms, but the neurotoxic effects of bisphenol substitutes such as bisphenol F (BPF) and S (BPS) have not been well investigated. We investigated the associations between BPA, BPF, and BPS with ADHD symptoms at multiple time points in children. Methods: The levels of BPA (at ages 4, 6, and 8), BPF (at ages 6 and 8), and BPS (at ages 6 and 8) were measured in 619 children. Because of the low detection frequency of BPF and BPS levels, participants were divided into categories (97%), whereas BPF and BPS were less frequently detected (age 6: 17.5% for BPF and 42.0% for BPS; age 8: 51.6% for BPF and 73.3% for BPS). Doubling in BPA levels was associated with increased ARS scores by 4.7% (95% confidence intervals [CI]: 0.5, 9.2) at age 6. The association was greater with BPA levels higher than 3.0 μg/g creatinine (24.2% [95% CI: 15.5, 33.6] increase). The BPF ≥ LOD group had 10.8% (95% CI: 1.2, 21.4) higher ARS scores than the BPF

Background: Pyrethroid insecticides are commonly used in residential settings, and their use has increased rapidly. Although research has been scarce, they have been reported to be associated with impaired neurodevelopment. Moreover, susceptible exposure windows and the long-term effects of pyrethroids have not been investigated. We examined the association between pyrethroid exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms over time, with exposure windows spanning from the prenatal period to school-age. Methods: Using 524 mother–child pairs, we measured urinary concentrations of 3-phenoxybenzoic acid (3-PBA), a major pyrethroid metabolite, and asked parents to fill-out the ADHD Rating Scale IV (ARS). We used Poisson regression to identify the susceptible periods of pyrethroid exposure, by correlating various 3-PBA exposure windows (prenatal, ages 2, 4, 6 and 8) with ADHD symptoms at ages 6 and 8. Results: Doubling of prenatal and age 2 3-PBA concentrations was associated with increased ADHD symptoms at age 6 (2.7% change, 95% confidence interval [CI]: 0.3, 5.2; 5.2% change [95% CI: 0.5, 10.2], respectively). The 3-PBA concentrations at age 4 and age 6 were linked with ADHD symptoms at age 8 (2.7% change [95% CI: 0.3, 5.3]; 3.3% change [95% CI: 0.2, 6.4], respectively). There were no clear sex-specific patterns in association. Discussion: Both prenatal and early-childhood exposure to 3-PBA were found to be associated with ADHD symptoms. Exposure during pregnancy, and at ages 2 to 6 were found to be susceptible periods for pyrethroid neurotoxicity at ages 6 and 8.

BackgroundHyperuricemia 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.MethodsFrom 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.ResultsMean 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.DiscussionsUrinary 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.

Background: Phthalates are synthetic chemicals with endocrine-disrupting properties. They are reportedly associated with various neurotoxic outcomes. Studies on exposure to phthalates and children’s autistic traits have shown inconsistent results with respect to sex and susceptible time periods. We investigated the association of phthalate exposure during the prenatal period and childhood with autistic traits over time using a birth cohort in South Korea. Methods: Five phthalate metabolites were measured during mid-term pregnancy and children's follow-up at ages of 4, 6, and 8 years among a total of 547 mother–child pairs. The social communication questionnaire (SCQ) was used to assess autistic traits of children at each time point. The relationship between phthalate metabolites and SCQ scores were analyzed by exposure windows and sex. Results: A 2.7 fold increase in di-(2-ethylhexyl) phthalate metabolite levels, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) during pregnancy was associated with increased SCQ scores at 4 years by 8.5% (95% confidence intervals [CI]: 1.9%, 15.5%) and 7.4% (95% CI: 0.3%, 15.0%), respectively, but not at the age of 6 or 8 years. Moreover, MEHHP levels at ages of 4 and 8 years were associated with increased SCQ scores at 8 years by 9.9% (95% CI: 1.8%, 18.6%) and 9.6% (95% CI: 1.3%, 18.6%), respectively. Boys showed stronger associations between phthalate exposure and SCQ scores than girls. Conclusion: The study suggested different susceptible time windows of phthalate exposure: exposure during pregnancy is associated with autistic traits in young children, whereas exposure during early childhood years leads to autistic traits in school-aged children, particularly boys.

Background: Humans are exposed to a mixture of metals during their lifetime; however, evidence of neurotoxicity of such mixtures in critical time windows is still insufficient. We aimed to elucidate the associations of four metals mixture across multiple time points with children’s intelligence quotient (IQ) in a prospective cohort study. Methods: Prenatal exposure and exposure at age 4 and 6 years to four types of blood metals, namely lead, mercury, cadmium, and manganese were quantified in 502 pregnant women and their children who participated in the Environment and Development Cohort study. Children’ s IQ scores were assessed using the Wechsler Intelligence Scale at age 6. Bayesian kernel machine regression (BKMR), quantile g-computation models, and elastic net (ENET) models were used to assess the associations of their blood metals mixture with IQ scores. Results: Multivariate linear regression models indicated that postnatal blood manganese exposure at the age of 4 years was significantly negatively associated with children’s IQ [β = − 5.99, 95% confidence interval (CI): −11.37 to − 0.61]. In the multi-chemical BKMR and quantile g-computation model, statistically significant inverse associations were found between the mixture of prenatal and postnatal metals and children’s IQ score (Difference in children’ IQ per quartile increase: −2.83; 95% CI: −5.28, −0.38). Interestingly, we found that manganese levels at both age of 4 and 6 years were contributing factors to children’s IQ in the mixture models, namely, BKMR, quantile g-computation, and ENET models. Conclusions: Multi-pollutant mixtures of prenatal and postnatal exposures to four metals affected child IQ at 6 years of age. We found a relationship between manganese exposure at both age 4, and 6 years and children’s IQ. Additional studies are warranted to confirm these associations and to control the exposure to different metals during pregnancy and preschool childhood.

The hippocampus, which engages in the process of consolidating long-term memories and learning, shows active development during childhood and adolescence. The hippocampus also functionally influences attention. Based on the influence of hippocampal function on attention, it was expected that the volume of the hippocampus would be associated with the difference in attention during childhood and adolescence, in which the brain develops actively. Thus, this study examined the association between hippocampal volume and attention metrics measured by the continuous performance test (CPT) in 115 children and adolescents (mean age = 12.43 ± 3.0, 63 male and 52 female). In association studies with both auditory and visual attention, we found that the bilateral hippocampal volumes showed negative relationships with auditory omission errors. A smaller volume of the left hippocampus also led to a longer auditory response time. However, visual attention did not show any significant relationship with the hippocampal volume. These findings were consistent even after adjusting for the effects of the related covariates (e.g., age, insomnia, and depression). Taken together, this study suggested that the increase in hippocampal volume during childhood and adolescence was associated significantly with better auditory attention.

Background: During late childhood and adolescence, the frontal lobe undergoes critical developmental changes, affecting a wide range of executive functions significantly. Conversely, abnormality in the maturation of the frontal lobe during this period may result in a limited ability to effectively use various executive functions. However, at present, it is still unclear how the structural development of the frontal lobe is associated with different aspects of executive functions during this developmental period. To fill the gap in evidence, we aimed to elucidate gray matter volume (GMV) in the frontal lobe and its relationship with multiple aspects of executive functions in late childhood and adolescence.Methods: We recruited our participants aged between 6 and 17 years to assess GMV in the frontal lobe and its relationship with different domains of executive functions in late childhood and adolescence. We used the voxel-based morphometry–DARTEL procedure to measure GMVs in multiple frontal sub-regions and Stroop test and Advanced Test of Attention (ATA) to measure executive functions. We then conducted partial correlation analyses and performed multiple comparisons with different age and sex groups.Results: Overall, 123 participants took part in our study. We found that many regional GMVs in the frontal lobe were negatively correlated with ATA scores in participants in late childhood and positively correlated with ATA scores in participants in adolescence. Only a few correlations of the GMVs with Stroop test scores were significant in both age groups. Although most of our results did not survive false discovery rate (FDR) correction (i.e., FDR

Background: The Mothers and Children's Environmental Health study (MOCEH) is a multi-centric prospective birth cohort study investigating effects of various environmental pollutants like heavy metals, endocrine disruptors, air pollutants, nutrition and lifestyle on birth outcomes, growth and development, health and disease of children. In this study, we report all the outcomes from the MOCEH study describing the different environmental pollutants affecting children’s health and disease. Methods: In MOCEH study, 1,751 pregnant women in their first trimester were recruited at 3 centers from 2006 to 2010 in South Korea. The children were followed from birth up to 6 years. Information on health outcomes of children including birth parameters, demographic characteristics, medical and child-rearing history, and nutritional status, were repeatedly obtained through the follow-ups by questionnaires administration, clinical evaluation, and biological specimen collection and measurements. Prenatal and postnatal measurement in biospecimen, i.e., lead, mercury, cadmium, manganese, 1-hydroxypyrene, 2-naphthol, malonadialdehyde, hippuric acid, bisphenol A and phthalate metabolites, and measurement in air samples, i.e., particulate matter, nitrogen dioxide, and total volatile organic compounds were performed. Results: The results show the adverse effect of prenatal exposure to heavy metals like mercury, lead and cadmium on children’s physical, cognitive and neurobehavioral development. Exposure to endocrine disruptors, air pollution, second hand smoke, and mother’s lifestyle during pregnancy affects children’s growth and development. We also identified specific window periods of exposure of pollutants significantly related to children’s health outcomes. Conclusion: The collective results from MOCEH study provide strong scientific evidence that exposures to prenatal and postnatal environmental pollutants have a negative effect on growth and development of children, which will be useful in implementing effective national policy to improve children’s environmental health. Keywords: Birth cohort, Children Environmental health, Environmental pollutants

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. [ABSTRACT FROM AUTHOR]

Childhood obesity could contribute to adulthood obesity, leading to adverse health outcomes in adults. However, the mechanisms for how obesity is developed are still unclear. To determine the epigenome-wide and genome-wide expression changes related with childhood obesity, we compared microRNome and transcriptome levels as well as leptin protein levels in whole bloods of 12 obese and 24 normal children aged 6 years. miR-328-3p, miR-1301-3p, miR-4685-3p, and miR-6803-3p were negatively associated with all obesity indicators. The four miRNAs were also associated with 3948 mRNAs, and separate 475 mRNAs (185 among 3948 mRNAs) were associated with all obesity indicators. The 2533 mRNAs (64.2%) among the 3948 mRNAs and 286 mRNAs (60.2%) among the 475 mRNAs were confirmed as targets of the four miRNAs in public databases through miRWalk 2.0. Leptin protein was associated with miR-6803-3p negatively and all obesity indicators positively. Using DAVID bioinformatics resources 6.8, top three pathways for obesity-related gene set were metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. The top three obesity-related disease classes were metabolic, cardiovascular, and chemdependency. Our results support that childhood obesity could be developed through miRNAs-related epigenetic mechanism and, further, these obesity-related epigenetic changes could control the pathways related with the development of various diseases.

Abstract Objective The majority of studies on the associations between breastfeeding and cognitive functioning have focused on IQ, with only a few investigating learning skills, and none of the latter adjusting for maternal IQ. We examined the association between breastfeeding and learning abilities in school-aged children using a cross-sectional design. Methods We recruited 868 children, aged 8–11 years and parents completed the Learning Disability Evaluation Scale (LDES). Multivariable linear regression models were used and age, gender, area of residence, annual family income, maternal education, and maternal age at delivery, were included as covariates. Maternal IQ was added to further adjust for the effects of maternal cognitive ability. Path analysis was conducted to investigate the mediation effect of maternal IQ between breastfeeding and learning skills. Results Children who were ever-breastfed had higher learning quotient scores on the LDES (p = 0.001) as well as higher scores on subscales related to speaking (p = 0.001), reading (p = 0.005), writing (p = 0.004), spelling (p = 0.003), and mathematical calculation (p = 0.003) than the never-breastfed participants. All of these variables remained significant after adjusting for gestational and socioeconomic factors and for maternal IQ as covariates. The path analysis showed that breastfeeding had both indirect and direct effects on the learning quotient. Conclusions The results suggest that breastfeeding is positively associated with learning skills in school-aged children.

The involvement of mitochondrial dysfunction in the pathophysiology of attention-deficit hyperactivity disorder (ADHD) has been suggested in several reports. Mitochondrial DNA (mtDNA) copy number as well as methylation of the D-loop region and peroxisome-proliferator-activated receptor γ co-activator-1α (PPARGC1A) are considered biomarkers for mitochondrial dysfunction. We compared the mtDNA copy number and methylation ratio of the D-loop region and PPARGC1A between ADHD patients and controls and also among ADHD subtypes. The present study included 70 subjects with ADHD and 70 age- and gender-matched healthy controls (HCs). We measured the relative mtDNA copy number in peripheral blood cells using quantitative polymerase chain reaction (qPCR), and the methylation ratio was measured using methylation-specific PCR (MSP) after bisulfite conversion. The relative mtDNA copy number was significantly higher in ADHD patients than in HCs (p = 0.028). The mtDNA methylation ratio of PPARGC1A was decreased in ADHD patients compared with HCs (p = 0.008). After adjusting for IQ level, only the mtDNA copy number differed between the ADHD and HCs (p = 0.01). There was a significant difference in the methylation ratio of PPARGC1A among ADHD subtypes. These results suggest the possible involvement of mitochondrial dysfunction in the pathophysiology of ADHD. Further large cohort studies investigating the correlation between clinical markers and biomarkers of mitochondrial dysfunction are warranted.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that arises from a complex interaction of environmental and genetic factors. Despite numerous pharmacological and behavioral interventions, approximately 10% of patients remain refractory. High-frequency deep brain stimulation (HF-DBS) has shown promising results for treatment-refractory OCD. We report the follow-up result of up to 6 years of 4 treatment-refractory OCD patients treated by HF-DBS. Targets of stimulation were the anterior limb of the internal capsule (ALIC) in two cases, and the nucleus accumbens (NAc) in the remaining cohort. The clinical profiles were quantified by the Yale-Brown obsessive-compulsive scale (Y-BOCS). Highly significant reductions in Y-BOCS scores were obtained from all patients during the follow-up period. A greater that 90% reduction in Y-BOCS, observed in the most successful case, was achieved with NAc HF-DBS. Y-BOCS scores in the other patients consistently achieved over 50% reductions in OCD symptoms. FDG-PET imaging indicated post-surgical reductions in metabolism, in not only targeted limbic networks, but also other frontal cortical and subcortical regions, suggesting that large-scale network modulation and inhibitions are associated with functional recovery in OCD. This study demonstrates that HF-DBS targeted to the ALIC and NAc is a safe and effective method for ameliorating intractable, treatment-refractory OCD symptoms. The NAc appeared to be the superior target for symptom reduction, and local inhibition of NAc activity and reduced frontal metabolism are key therapeutic indications.