Prenatal and postnatal exposure to bisphenol A (BPA) may affect early brain development. Rodent studies suggest that prenatal and postnatal neurodevelopmental toxicity from BPA exposure may manifest as social deficits in offspring. We investigated the association between prenatal and postnatal exposure to BPA and social impairments in a sample of 4-year-old children. We recruited second-trimester pregnant women between 2008 and 2011, and measured their creatinine-adjusted prenatal urine BPA levels. In 2014-2015, a subset of 4-year-old children born to these women underwent neurobehavioral assessment and physical examination. We collected urine and blood from the children and assessed social impairments, including deficits in social interaction, social communication, and other behavior patterns using the Korean version of the Social Communication Questionnaire (K-SCQ) (n = 304). We examined social impairments associated with prenatal exposure at mid-term pregnancy and postnatal exposure to BPA at 4 years of age, using linear and piecewise linear regression models. The relationship between prenatal BPA exposure and social communication was non-linear and statistically significant at or above the flexion point for BPA levels of 3.0 μg/g creatinine in girls (58.4%, 95% confidence interval [CI], 6.5% to 135.8%). Each 2-fold increase in postnatal BPA exposure was significantly associated with an 11.8% (95% CI, 0.6% to 24.3%) increase in impairment in social communication in 4-year old girls, as indicated by the linear regression model. Prenatal and postnatal BPA exposure is associated with social impairment at 4 years of age, particularly in girls.

Previous studies have reported varying findings regarding the association of brain connectivity in autism spectrum disorder (ASD) with overconnectivity, underconnectivity, or both. Despite the emerging understanding that ASD is a developmental disconnection syndrome, very little is known about structural brain networks in preschool‐aged children with low‐functioning ASD. We aimed to investigate the structural brain connectivity of low‐functioning ASD using diffusion magnetic resonance imaging and graph theory to examine alterations in different brain network topologies and identify any correlations with the clinical severity of ASD in preschool‐aged children. Fifty‐two preschool‐aged children (28 with ASD and 24 with typical development) were included in the analysis. Graph‐based network analysis was performed to examine the global and local structural brain networks. Nodal network measures exhibited increased nodal strength in the right Heschl's gyrus, which was positively associated with all autistic clinical symptoms (Autism Diagnostic Observation Schedule and Childhood Autism Rating Scale [CARS]). The nodal strength of the right inferior temporal gyrus showed a moderate correlation with the CARS score. Using network‐based statistics, we identified a subnetwork with increased connections encompassing the right Heschl's gyrus and the right inferior temporal gyrus in preschool‐aged children with ASD. The asymmetric value in the inferior temporal gyrus exhibited right dominance of nodal strength in children with ASD compared to that in typically developing children. Our findings support the theory of aberrant brain growth and overconnectivity as the underlying mechanism of ASD and provides new insights into potential regional biomarkers that can detect low‐functioning ASD in preschool‐aged children.Lay Summary: This study supports the theory of aberrant brain growth and overconnectivity as an explanation for ASD. Measuring the right HG and inferior temporal gyrus provides new insights of potential regional biomarkers underpinning ASD in preschool‐aged children.

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. 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. 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. 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.

Adolescence is a period of marked sleep pattern changes and sleep problems, which may result from both endogenous and exogenous factors. Among the various factors affecting adolescent sleep, depression and problematic Internet use (PIU) have received considerable attention. We examined if there is a different PIU effect on sleep between depressed group and non-depressed groups. Data for a total of 766 students’ between 7th and 11th grades were analyzed. We assessed various variables related sleep to problems and depression and compared those variables between an adolescent group with problematic Internet use (PIUG) and an adolescent group with normal Internet use (NIUG). One hundred fifty two participants were classified as PIUG, and 614 were classified as NIUG. Compared with the NIUG, the members of the PIUG were more prone to insomnia, excessive daytime sleepiness and sleep-wake behavior problems. The PIUG also tended to include more evening types than the NIUG. Interestingly, the effect of Internet use problems on sleep problems appeared to be different according to the presence or absence of the moderating effect of depression. When we considered the moderating effect of depression, the effect of Internet use problems on sleep-wake behavior problems, insomnia and excessive daytime sleepiness increased with increasing Young’s Internet Addiction Scale (IAS) scores in the non-depressed group. However, in the depressed group, the effects of Internet use problems on sleep-wake behavior problems and insomnia did not change with increasing Internet use problems, and the effect of Internet use problems on excessive daytime sleepiness was relatively decreased with increasing Internet use problems in the depressed group. This study demonstrated that the effect of PIU on sleep presented differently between the depressed and non-depressed groups. PIU is associated with poorer sleep in non-depressed adolescents but not in depressed adolescents. This finding might be observed because PIU may be the biggest contributor to sleep problems in the problematic Internet user without depression, but in the problematic Internet user with depression, depression might be a more important contributor to sleep problems; thus, the influence of PIU on sleep effect might be diluted.

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