The Association Between Functional Variants in Long Non-coding RNAs and the Risk of Autism Spectrum Disorder Was Not Mediated by Gut Microbiota.

The effect of functional variants in long non-coding RNA (lncRNA) gene regions on autism spectrum disorder (ASD) remains unclear. The present study aimed to investigate the association of functional variants located in lncRNA genes with the risk of ASD and explore whether gut microbiota would mediate the relationship. A total of 87 cases and 71 healthy controls were enrolled in the study. MassARRAY platform and 16S rRNA sequencing were respectively applied to assess the genotype of candidate SNPs and gut microbiota of children. The logistic regression models showed that the association between rs2295412 and the risk of ASD was statistically significant after Bonferroni adjustments. The risk of ASD decreased by 19% for each additional C allele carried by children in multiplicative models (OR = 0.81, 95% CI, 0.69-0.94, P = 0.007). Although we identified significant correlations between rs8113922 polymorphisms, Bifidobacteriales, and ASD, the mediating effect of gut microbiota on the relationship of the polymorphisms with the risk of ASD was not significant. The findings demonstrated that functional variants in lncRNA genes play an important role in ASD and gut microbiota could not mediate the association. Future studies are warranted to verify the results and search for more possible mechanisms of variants located in lncRNA genes implicated in ASD.

Exposure to ambient air pollution with depressive symptoms and anxiety symptoms among adolescents: A national population-based study in China.

BACKGROUND: Air pollution threatens adolescents' physical health and adversely affects adolescents' mental health. Previous studies mostly focused on the effects of air pollution on physical health, but there were few studies on the effects of air pollution on mental health. METHODS: We collected scores of depressive symptoms and anxiety symptoms from 15,331 adolescents from 43 schools in eleven provinces in September and November 2017. The data on air pollution comes from the China High Air Pollutants dataset, which included concentrations of particulate matter with diameters of ≤1.0 µm (PM1), diameters of ≤2.5 µm (PM2.5), and diameters of ≤10 µm (PM10), as well as nitrogen dioxide (NO2). The associations between air pollution and depressive and anxiety symptoms among adolescents were estimated using generalized linear mixed models. RESULTS: Depressive and anxiety symptoms among Chinese adolescents were 16% and 32%, respectively. In the adjusted model, an interquartile range (IQR) increase from PM2.5 was associated with the odds of anxiety symptoms [odds ratio (OR) = 1.01; 95% confidence interval (CI): 1.00, 1.01, P = 0.002]. Also, an IQR increase in PM10 was significantly associated with the odds of anxiety symptoms (OR = 1.01; 95% CI: 1.00, 1.01, P = 0.029). Compared with the lowest quartile, the adjusted OR of anxiety symptoms for the highest quartile of PM2.5 and PM10 were 1.29 (1.15, 1.44) and 1.23 (1.06, 1.42), respectively. In addition, the association between PM2.5 and depressive symptoms was significant. The robustness of the results was also confirmed by stratification and sensitivity analyses. CONCLUSIONS: Exposure values for airborne particulate matter were associated with depressive symptoms and anxiety symptoms in adolescents, particularly for PM2.5 and PM10 with anxiety symptoms among adolescents.

Associations between dyslexia and children's mental health: Findings from a follow-up study in China.

Dyslexia is a common learning difficulty that can lead to adverse health outcomes and socioeconomic difficulties. Evidence from longitudinal studies on the association between dyslexia and psychological symptoms in children is limited. Moreover, the psychological trends of children with dyslexia are unclear. In this study, we enrolled 2,056 students in Grades 2 to 5, including 61 dyslexic children, who participated in three mental health surveys and dyslexia screening. All the children were surveyed for symptoms of stress, anxiety and depression. We used generalized estimating equation models to estimate changes in psychological symptoms of children with dyslexia over time and the association between dyslexia and psychological symptoms. The results showed that dyslexia was associated with stress and depressive symptoms in children in both crude (ß = 3.27, 95% confidence interval [CI] [1.89∼4.65], ß=1.20, 95%CI: [0.45∼1.94], respectively) and adjusted models (ß = 3.32, 95%CI: [1.87∼4.77], ß=1.31, 95%CI: [0.52∼2.10], respectively). In addition, we found no significant differences in the emotional status of dyslexic children in either survey. Dyslexic children are at risk for mental health issues, and persistent emotional symptoms. Therefore, interventions regarding not only reading ability but also psychological conditions should be pursued.

Association between urinary 2-hydroxyethyl mercapturic acid and dyslexia among school-aged children.

Ethylene oxide is commonly used in industrial synthesis and medical disinfection. It is a known human carcinogen and has neurotoxicity. However, the association between ethylene oxide exposure and neurodevelopmental disorders remains unclear. This study aimed to evaluate the association between urinary concentrations of 2-hydroxyethyl mercapturic acid (HEMA; metabolite of ethylene oxide) and dyslexia among school-aged children. A total of 355 dyslexic children and 390 controls from three cities in China were enrolled in this case-control study from November 2017 to December 2020. Urinary HEMA was detected in 100% of the urine samples, suggesting widespread exposure to ethylene oxide in the children. Notably, the children with dyslexia had higher concentrations of urinary HEMA compared to the controls (geometric mean: 2.92 vs. 2.47 ng/mL) (P = 0.004). In the multivariable-adjusted model, urinary concentrations of HEMA were significantly associated with dyslexia risk. The individuals within the highest HEMA concentration demonstrated a 1.97-fold increased odds of dyslexia compared to those within the lowest quartile (95% confidence interval: 1.20-3.23). Thus, these findings suggested the possible link between HEMA levels and the risk of dyslexia. Further studies are warranted to validate this finding and illustrate the underlying mechanism.

Combining multi-omics approaches to prioritize the variant-regulated functional long non-coding RNAs in autism spectrum disorder.

OBJECTIVE: Rising evidence has indicated that long non-coding RNA (lncRNA) may play an essential role in the development of autism spectrum disorder (ASD). However, identifying the lncRNAs associated with ASD and the risk loci on them remains a major challenge. This study aims to identify potential causative variants and explore the related mechanisms. METHODS: By leveraging differential expression analysis, WGCNA analysis and cis-expression quantitative analysis, our study mined functional SNPs with the regulated long non-coding RNA genes in brain tissues. We recruited 611 ASD children and 645 healthy children in the case-control study. RESULTS: Total 68 different expressed lncRNAs were validated by calculating the brain tissue-specific expression using RNA-seq data. By the WGCNA method, 9 functional lncRNAs classified as e-lncRNA were found to interact with 976 ASD risk genes. Furthermore, we mined functional SNPs regulated long non-coding RNAs in brain tissues. We analyzed the association between candidate SNPs and ASD risks in Chinese children, which showed BDNF-AS rs1565228 allele G to C reduced the risk of ASD (OR = 0.81, 95%CI: 0.66-0.98). Further bioinformatics analysis showed that the variant rs1565228 C>G with the low binding affinity of transcription factor SRF caused the decreased expression of lncRNA BDNF-AS. Our study revealed that rs2295412 in the non-coding sequence of the lncRNA gene region was significantly associated with the risk of ASD. DISCUSSION: These findings suggested that the SNPs in the non-coding region of lncRNA may play important roles in the genetic susceptibility of ASD, which may facilitate the early screening of ASD.

Associations of greenness surrounding schools and self-reported depressive and anxiety symptoms in Chinese adolescents.

BACKGROUND: The effect of school-based greenness exposure on mental health among adolescents remains unclear. The study aimed to estimate the associations between school-based greenness and depressive and anxiety symptoms among adolescents and explore potential modifier and mediator between the associations. METHODS: A cross-sectional survey involving 15,559 adolescents was conducted in China. The Chinese version of the Center for Epidemiologic Studies Depression 9-Item Scale and the Generalized Anxiety Disorder 7-Item Scale were used to assess the depressive and anxiety symptoms among adolescents. The Normalized Difference Vegetation Index within a 400 m and 800 m zone surrounding schools was used to indicate the adolescents' exposure to greenness. We estimated daily concentrations of PM1.0, PM2.5, and NO2 from the China High Air Pollutants dataset. Multiple logistic regression models were used. RESULTS: Higher exposure to greenness surrounding schools was negatively associated with depressive (OR: 0.774, 95%CI: 0.685-0.875) and anxiety symptoms (0.740, 0.669-0.818). We observed stronger associations between greenness and depressive and anxiety symptoms among girls, lower age group (11-15 years), and adolescents born to parents with lower education levels. PM1.0 (proportion mediated estimates: 14.3 %; 95 % CI: 4.2 %, 24.5 %) and PM2.5 (10.5 %; 95 % CI: 3.0 %, 17.9 %) mediated the associations between greenness exposure and depressive symptoms. The number of days adolescents attended physical education classes per week mediated -22.8 % (95 % CI: -38.5 %, -7.1 %) and -9.7 % (95 % CI: -15.5 %, -3.8 %) of the effects of greenness on depressive and anxiety symptoms. CONCLUSIONS: Increasing the greenness and improving the environment surrounding schools is effective in promoting the mental health of adolescents.