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Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P = 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P = .0144) and ADHD (P = .0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients’ underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6–12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial’s primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.

Background: This study examined the effect of nutrition education given by dietitians to families of children aged 3–18 diagnosed with autism spectrum disorder (ASD) on meal consumption, eating behaviors, autism severity, serum oxidant/antioxidant marker levels, and total dietary antioxidant capacity. Methods: The project was carried out with 44 pediatric patients diagnosed with ASD and their parents. The ELISA method was used for antioxidant and oxidant measurements, and the oxygen radical absorbance capacity values ​​of foods defined according to the BeBiS program were used to calculate the total dietary antioxidant capacity. The children's eating behavior questionnaire, childhood autism rating scale (CARS), and brief autism mealtime behavior inventory (BAMBI) were administered. Results: There was no significant difference in antioxidant and oxidant parameters between the experimental and control groups. At the end of eight weeks, superoxide dismutase and glutathione levels increased significantly in the experimental group. There was no significant difference in terms of the families of the autistic children in the experimental and control groups or their disease‐specific knowledge. BAMBI scores were similar between the groups at baseline, while a significant decrease was observed in the experimental group at the end of the study. Daily energy, saturated fatty acid (SFA), carbohydrate, and omega‐6 intake decreased, while protein, fat, mono‐ and poly‐unsaturated fatty acid, and omega‐3 intake increased in the experimental group following nutrition education. However, these results were not statistically significant. There was no significant difference in terms of micronutrient intake between children with ASD in experimental and control groups before and after nutrition education. Conclusion: Improvements in eating habits and dietary patterns were noted after nutrition education, especially in the experimental group, even though there were no appreciable changes in oxidative stress indicators. These behavioral shifts imply that family nutrition education can be extremely important in encouraging better eating practices and improving the general well‐being of kids with ASD and their families. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that produces symptoms from the early years of life. This study was conducted to examine the effect on total antioxidant capacity and antioxidant–oxidant parameters in the diet in children of nutrition education provided by specialist dieticians for the families of children diagnosed with ASD aged 3–18 years. As a result, it shows that the nutrition education provided helps children with ASD acquire healthy nutrition and eating habits, prevents nutritional deficiencies, alleviates nutrition‐related symptoms, ensures healthy growth and development, improves the quality of life of families, and reduces stress factors.

Background Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD. Results Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators’ changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P  < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P  > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05). Conclusions Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms. Trial registration The study protocol was peer reviewed and approved by the institutional review board of Children’s Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).

Background Autism spectrum disorder (ASD) has been associated with brain inflammation as indicated by the activation of microglia, but the triggers are not known. Extracellular vesicles (EVs) are secreted from many cells in the blood and other biological fluids and carry molecules that could influence the function of target cells. EVs have been recently implicated in several diseases, but their presence or function in ASD has not been studied. Methods EVs were isolated from the serum of children with ASD ( n  = 20, 16 males and 4 females, 4–12 years old) and unrelated age and sex-matched normotypic controls ( n  = 8, 6 males and 2 females, 4–12 years old) using the exoEasy Qiagen kit. EVs were characterized by determining the CD9 and CD81 membrane-associated markers with Western blot analysis, while their morphology and size were assessed by transmission electron microscopy (TEM). Human microglia SV40 were cultured for 24 h and then stimulated with EVs (1 or 5 μg/mL), quantitated as total EV-associated protein, for 24 or 48 h. IL-1β secretion was measured by ELISA. The results were analyzed using the Mann-Whitney U non-parametric test, and all statistical analyses were performed using Graph Pad Prism 5. Results EVs were isolated and shown to be spherical structures (about 100 nm) surrounded by a membrane. Total EV-associated protein was found to be significantly increased ( p  = 0.02) in patients as compared to normotypic controls. EVs (5 μg/mL) isolated from the serum of patients with ASD stimulated cultured human microglia to secrete significantly more of the pro-inflammatory cytokine interleukin IL-1β (163.5 ± 13.34 pg/mL) as compared to the control (117.7 ± 3.96 pg/mL, p  < 0.0001). The amount of mitochondrial DNA (mtDNA7S) contained in EVs from children with ASD was found to be increased ( p  = 0.046) compared to the normotypic controls. Conclusions These findings provide novel information that may help explain what triggers inflammation in the brain of children with ASD and could lead to novel effective treatments.

This study is the first to investigate potential correlations between blood groups, Rh factors, and Autism Spectrum Disorder (ASD) within a diverse dataset of 2,390 participants from multiple regions in Iraq. The participants included children with ASD, children with other neurodevelopmental disorders, typically developing children and their parents. Using chi-square tests, logistic regression analysis, and machine learning algorithms, the findings revealed that the O + blood group was the most prevalent across all groups. Importantly, logistic regression analysis identified the AB + blood group as being associated with a significantly lower risk of ASD, suggesting a novel protective factor. No significant associations were observed between other blood groups, Rh factors, and ASD risk. Additionally, the study found no statistically significant differences in blood group distributions among children with ASD, other neurodevelopmental disorders, and typically developing children. These results provide new insights into the potential immunogenetic contributions to ASD and emphasize the need for further research to confirm the protective effect of the AB + blood group. Such studies may help unravel the genetic, immunological, and environmental mechanisms underlying ASD and support the development of targeted diagnostic and preventative strategies.

Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD.

The purpose of this study was to investigate the expression of miR-499a-5p in children with autism spectrum disorders (ASD) and its value in early diagnosis of ASD. This is a retrospective case–control study that included 40 children with ASD as a case group and 43 healthy children as a control group. Magnetic resonance imaging (MRI) was performed on all subjects, and the children were scored with childhood autism rating scale (CARS) and autism behavior checklist (ABC). The expression of miR-499a-5p in serum was detected by RT-qPCR, and the diagnostic value of miR-499a-5p in ASD was evaluated by ROC curve. Pearson correlation coefficient was used to evaluate the correlation between miR-499a-5p levels and scores. Compared with healthy children, the expression level of serum miR-499a-5p was significantly reduced in children with ASD. ROC curve showed that miR-499a-5p is of high diagnostic value for ASD. The results of MRI suggested that the volume of the amygdala in ASD children was significantly larger than that in healthy children, while the volume of the caudate nucleus was significantly reduced. Correlation results showed that the scores of CARS and ABC in the ASD group were significantly negatively correlated with the levels of miR-499a-5p. In the ASD group, the volume of the amygdala was negatively correlated with the level of miR-499a-5p, while the volume of the caudate nucleus was positively correlated with the level of miR-499a-5p. The decreased expression of miR-499a-5p in the serum of children with ASD was significantly related to the changes in brain volume of children with ASD, and the miRNA showed good diagnostic accuracy in children with ASD.

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy donors by real-time quantitative PCR. All of the tested markers showed quantifiability, accuracy and reproducibility. We then compared the expression levels of those markers in PBMCs taken from ASD patients in response to orally-delivered sulforaphane. The mRNA levels of cytoprotective enzymes (NQO1, HO-1, AKR1C1), and heat shock proteins (HSP27 and HSP70), increased. Conversely, mRNA levels of pro-inflammatory markers (IL-6, IL-1β, COX-2 and TNF-α) decreased. Individually none is sufficiently specific or sensitive, but when grouped by function as two panels, these biomarkers show promise for monitoring pharmacodynamic responses to sulforaphane in both healthy and autistic humans, and providing guidance for biomedical interventions.

The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment. Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD. A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set. This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.