Transcript levels of 4 genes in umbilical cord blood are predictive of later autism development: a longitudinal follow-up study.

BACKGROUND: Over recent decades, autism spectrum disorder (ASD) has been of increasing epidemiological importance, given the substantial increase in its prevalence; at present, clinical diagnosis is possible only after 2 years of age. In this study, we sought to develop a potential predictive model for ASD screening. METHODS: We conducted a longitudinal follow-up study of newborns over 3 years. We measured transcript levels of 4 genes (superoxide dismutase-2 [SOD2], retinoic acid-related orphan receptor-α [RORA], G protein-coupled estrogen receptor-1 [GPER], progesterone receptor [PGR]), 2 oxidative stress markers and epigenetic marks at the RORA promoter in case-control umbilical cord blood mononuclear cell (UCBMC) samples. RESULTS: We followed 2623 newborns; we identified 41 children with ASD, 63 with delayed development and 2519 typically developing children. We matched the 41 children with ASD to 41 typically developing children for UCBMC measurements. Our results showed that children with ASD had significantly higher levels of H3K9me3 histone modifications at the RORA promoter and oxidative stress in UCBMC than typically developing children; children with delayed development showed no significant differences. Children with ASD had significantly lower expression of SOD2, RORA and GPER, but higher PGR expression than typically developing children. We established a model based on these 4 candidate genes, and achieved an area under the curve of 87.0% (standard deviation 3.9%) with a sensitivity of 1.000 and specificity of 0.854 to predict ASD in UCBMC. LIMITATIONS: Although the gene combinations produced a good pass/fail cut-off value for ASD evaluation, relatively few children in our study sample had ASD. CONCLUSION: The altered gene expression in UCBMC can predict later autism development, possibly providing a predictive model for ASD screening immediately after birth.

Network Analysis of ADHD Symptoms and Cognitive Profiles in Children.

Purpose: Although many studies have reported the cognitive profiles in attention-deficit/hyperactivity disorder (ADHD), the interactions between ADHD symptoms and the patients' cognitive profiles have not been carefully examined through the network analysis. Here, in this study, we systematically analyzed the ADHD patents' symptoms and cognitive profiles, and identified a set of interactions between ADHD symptoms and cognitive domains using the network approach. Patients and Methods: A total of 146 children with ADHD, 6 to 15 years of age, were included in the study. All participants were assessed by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) test. The patients' ADHD symptoms were evaluated by the Vanderbilt ADHD parent and teacher rating scales. GraphPad Prism 9.1.1 software was used for descriptive statistics and R 4.2.2 was used for network model construction. Results: The ADHD children in our sample showed lower scores for full scale intelligence quotient (FSIQ), verbal comprehension index (VCI), processing speed index (PSI) and working memory index (WMI). Among all the ADHD core symptoms and comorbid symptoms, the academic ability, inattention symptoms and mood disorder showed direct interaction with the cognitive domains of WISC-IV. In addition, oppositional defiant of the ADHD comorbid symptoms, and perceptual reasoning of the cognitive domains exhibited the highest strength centrality in the ADHD-Cognition network based on parent ratings. Classroom behaviors of the ADHD functional impairment, and verbal comprehension of the cognitive domains exhibited the highest strength centrality in the network based on teacher ratings. Conclusion: We highlighted the importance of considering the interactions between the ADHD symptoms and cognitive properties when designing the intervention plans for the ADHD children.

Berberine Ameliorates Prenatal Dihydrotestosterone Exposure-Induced Autism-Like Behavior by Suppression of Androgen Receptor.

Many epidemiology studies have shown that maternal polycystic ovary syndrome (PCOS) results in a greater risk of autism spectrum disorders (ASD) development, although the detailed mechanism remains unclear. In this study, we aimed to investigate the potential mechanism and provide a possible treatment for PCOS-mediated ASD through three experiments: Experiment 1: real-time PCR and western blots were employed to measure gene expression in human neurons, and the luciferase reporter assay and chromatin immunoprecipitation (ChIP) was used to map the responsive elements on related gene promoters. Experiment 2: pregnant dams were prenatally exposed to dihydrotestosterone (DHT), androgen receptor (AR) knockdown (shAR) in the amygdala, or berberine (BBR), and the subsequent male offspring were used for autism-like behavior (ALB) assay followed by biomedical analysis, including gene expression, oxidative stress, and mitochondrial function. Experiment 3: the male offspring from prenatal DHT exposed dams were postnatally treated by either shAR or BBR, and the offspring were used for ALB assay followed by biomedical analysis. Our findings showed that DHT treatment suppresses the expression of estrogen receptor ß (ERß) and superoxide dismutase 2 (SOD2) through AR-mediated hypermethylation on the ERß promoter, and BBR treatment suppresses AR expression through hypermethylation on the AR promoter. Prenatal DHT treatment induces ERß suppression, oxidative stress and mitochondria dysfunction in the amygdala with subsequent ALB behavior in male offspring, and AR knockdown partly diminishes this effect. Furthermore, both prenatal and postnatal treatment of BBR partly restores prenatal DHT exposure-mediated ALB. In conclusion, DHT suppresses ERß expression through the AR signaling pathway by hypermethylation on the ERß promoter, and BBR restores this effect through AR suppression. Prenatal DHT exposure induces ALB in offspring through AR-mediated ERß suppression, and both prenatal and postnatal treatment of BBR ameliorates this effect. We conclude that BBR ameliorates prenatal DHT exposure-induced ALB through AR suppression, this study may help elucidate the potential mechanism and identify a potential treatment through using BBR for PCOS-mediated ASD.