1. Alexander-Howden B, Zhang L, van der Sloot AM, Tollis S, St-Cyr DJ, Sicheri F, Bird AP, Tyers M, Lyst MJ. A screen for MeCP2-TBL1 interaction inhibitors using a luminescence-based assay. Sci Rep;2023 (Mar 8);13(1):3868.

Understanding the molecular pathology of neurodevelopmental disorders should aid the development of therapies for these conditions. In MeCP2 duplication syndrome (MDS)-a severe autism spectrum disorder-neuronal dysfunction is caused by increased levels of MeCP2. MeCP2 is a nuclear protein that binds to methylated DNA and recruits the nuclear co-repressor (NCoR) complex to chromatin via an interaction with the WD repeat-containing proteins TBL1 and TBLR1. The peptide motif in MeCP2 that binds to TBL1/TBLR1 is essential for the toxicity of excess MeCP2 in animal models of MDS, suggesting that small molecules capable of disrupting this interaction might be useful therapeutically. To facilitate the search for such compounds, we devised a simple and scalable NanoLuc luciferase complementation assay for measuring the interaction of MeCP2 with TBL1/TBLR1. The assay allowed excellent separation between positive and negative controls, and had low signal variance (Z-factor = 0.85). We interrogated compound libraries using this assay in combination with a counter-screen based on luciferase complementation by the two subunits of protein kinase A (PKA). Using this dual screening approach, we identified candidate inhibitors of the interaction between MeCP2 and TBL1/TBLR1. This work demonstrates the feasibility of future screens of large compound collections, which we anticipate will enable the development of small molecule therapeutics to ameliorate MDS.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bernard S, Doherty M, Porte H, Al-Bustani L, Murphy LE, Russell MC, Shaw SCK. Upholding autistic people’s human rights: A neurodiversity toolbox for autism research. Autism Res;2023 (Mar 7)

Lien vers le texte intégral (Open Access ou abonnement)

3. Brochier A, Messmer E, Wexler MG, Rogers S, Cottrell E, Tripodis Y, Garg A. A cross-sectional study of relationships between social risks and prevalence and severity of pediatric chronic conditions. BMC Pediatr;2023 (Mar 8);23(1):115.

BACKGROUND: To examine the differential relationships between seven social risk factors (individually and cumulatively) with the prevalence and severity of asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and overweight/obesity in children. METHODS: Using the 2017-2018 National Survey of Children’s Health, we examined associations between social risk factors (caregiver education, caregiver underemployment, discrimination, food insecurity, insurance coverage, neighborhood support, and neighborhood safety) and the prevalence and severity of asthma, ADHD, ASD, and overweight/obesity. We used multivariable logistic regression to assess the relationship between individual and cumulative risk factors with each pediatric chronic condition, controlling for child sex and age. RESULTS: Although each social risk factor was significantly associated with increased prevalence and/or severity of at least one of the pediatric chronic conditions we investigated, food insecurity was significantly associated with higher disease prevalence and severity for all four conditions. Caregiver underemployment, low social support, and discrimination were significantly associated with higher disease prevalence across all conditions. For each additional social risk factor a child was exposed to, their odds of having each condition increased: overweight/obesity (aOR: 1.2, 95% CI: [1.2, 1.3]), asthma (aOR: 1.3, 95% CI: [1.2, 1.3], ADHD (aOR: 1.2, 95% CI: [1.2, 1.3]), and ASD (aOR: 1.4, 95% CI: [1.3, 1.5]). CONCLUSIONS: This study elucidates differential relationships between several social risk factors and the prevalence and severity of common pediatric chronic conditions. While more research is needed, our results suggest that social risks, particularly food insecurity, are potential factors in the development of pediatric chronic conditions.

Lien vers le texte intégral (Open Access ou abonnement)

4. Dehghani M, Jafarnezhadgero AA, Darvishani MA, Aali S, Granacher U. Effects of an 8-week multimodal exercise program on ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder. Trials;2023 (Mar 8);24(1):170.

BACKGROUND: Autism spectrum disorder is a developmental disability with first signs appearing in children aged 3 years and younger. Given that autism spectrum disorder is accompanied by a broad range of symptoms such as impaired sensory, neurological, and neuromotor functions, it appears plausible to argue that an intervention program focusing on multimodal exercise rather than single-mode exercise might be more effective in treating this wide variety of symptoms. OBJECTIVE: The aim of this study was to evaluate the effects of a multimodal exercise program entitled Sports, Play, and Active Recreation for Kids on variables of ground reaction forces and plantar pressure during walking in boys with autism spectrum disorder. METHODS: Twenty-four autism spectrum disorder boys aged 7-11 years were recruited and randomly allocated into an intervention or a waiting control group. Sports, Play, and Active Recreation for Kids was conducted over a period of 8 weeks with three weekly sessions. This training protocol includes aerobic dance and jump rope exercises as well as running games. Pre- and post-training, ground reaction forces and plantar pressure variables were recorded while walking at a constant walking speed of 0.9 m/s using a foot scan embedded in a 15-m walkway. RESULTS: Significant group-by-time interactions were found for the first peak of vertical ground reaction force, loading rate, and peak pressure at the medial heel region (all p = 0.001-0.49, d = 0.89-1.40). Post-hoc analyses showed significant pre-post decreases for the first peak of vertical ground reaction force (p = 0.001, d = 1.27), loading rate (p = 0.009, d = 1.11), and peak pressure at the medial heel region (p = 0.021, d = 1.01). CONCLUSIONS: Our results suggest that a joyful and multimodal exercise program has positive effects on kinetic walking characteristics of autism spectrum disorder boys. Accordingly, we recommend to implement this type of exercise in prepubertal autism spectrum disorder boys to improve gait kinetics. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20170806035517N4. Registered on November 8, 2021. This study was approved by the Ethical Committee of the University of Mohaghegh Ardabili, Ardabil, Iran (IR.UMA.REC.1400.019). The study was conducted in accordance with the latest version of the Declaration of Helsinki.

Lien vers le texte intégral (Open Access ou abonnement)

5. Doğan M, Albayrak Y, Erbaş O. Torasemide Improves the Propionic Acid-Induced Autism in Rats: A Histopathological and Imaging Study. Alpha Psychiatry;2023 (Jan);24(1):22-31.

OBJECTIVE: Autism spectrum disorder is a neurodevelopmental disease in which impaired social behaviors, impaired sociality, and restricted and repetitive behaviors are seen. Bumetanide is a loop diuretic that inhibits Na(+)-K(+)-2Cl(-) cotransporter 1 and it is currently used in clinical phase studies in patients with autism spectrum disorder. In present research, it is purposed to demonstrate the beneficial effects of torasemide which is another Na(+)-K(+)-2Cl(-) cotransporter 1 inhibitor on an experimental autism model induced with propionic acid by providing imaging and brain tissue investigations. METHODS: Male Wistar rats were used in the present study (n = 30). Propionic acid of 250 mg/kg/day was administrated intraperitoneally in rats to induce autism for 5 days. Three groups were created for present study as follows: group 1, normal control (n = 10); group 2, propionic acid and saline given group (n = 10); group 3, propionic acid + tora-semide-administrated group (n = 10). RESULTS: Torasemide group scored higher on behavioral tests compared to saline group. The brain levels of malondialdehyde, tumor necrosis factor-alpha, interleukin-2, interleukin-17, and Nuclear Factor kappa B (NF-κB), Glial fibrillary acidic protein (GFAP) were remarkably higher in propionic acid + saline group. In histopathology assessments, torasemide group had higher neuronal count of Cornu Ammonis 1, neuronal count of Cornu Ammonis 2 in hippocampus, and Purkinje cells in cerebellum. GFAP immunostaining index (Cornu Ammonis 1) and cerebellum were lower in torasemide group. Magnetic resonance spectroscopy revealed that mean lactate value was higher in propionic acid + saline group compared to torasemide group. CONCLUSION: Our experimental results showed that torasemide might enhance gamma-aminobutyric acid activity. Torasemide can be considered another promising Na(+)-K(+)-2Cl(-) cotransporter 1 inhibitor in the treatment of autism with a longer half-life and less side effects after further studies.

Lien vers le texte intégral (Open Access ou abonnement)

6. Flanagan E, Malmqvist E, Rittner R, Gustafsson P, Källén K, Oudin A. Exposure to local, source-specific ambient air pollution during pregnancy and autism in children: a cohort study from southern Sweden. Sci Rep;2023 (Mar 8);13(1):3848.

Evidence of air pollution exposure, namely, ambient particulate matter (PM), during pregnancy and an increased risk of autism in children is growing; however, the unique PM sources that contribute to this association are currently unknown. The aim of the present study was to investigate local, source-specific ambient PM exposure during pregnancy and its associations with childhood autism, specifically, and autism spectrum disorders (ASD) as a group. A cohort of 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on locally emitted PM with an aerodynamic diameter < 2.5 µm (PM(2.5)). A flat, two-dimensional dispersion model was used to assess local PM(2.5) concentrations (all-source PM(2.5), small-scale residential heating- mainly wood burning, tailpipe exhaust, and vehicle wear-and-tear) at the mother's residential address during pregnancy. Associations were analyzed using binary logistic regression. Exposure to local PM(2.5) during pregnancy from each of the investigated sources was associated with childhood autism in the fully adjusted models. For ASD, similar, but less pronounced, associations were found. The results add to existing evidence that exposure to air pollution during pregnancy may be associated with an increased risk of childhood autism. Further, these findings suggest that locally produced emissions from both residential wood burning and road traffic-related sources (tailpipe exhaust and vehicle wear-and-tear) contribute to this association.

Lien vers le texte intégral (Open Access ou abonnement)

7. Hong D, Iakoucheva LM. Correction to: Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology. Transl Psychiatry;2023 (Mar 7);13(1):80.

Lien vers le texte intégral (Open Access ou abonnement)

8. Ledoux N, Gauthier-Naud W, Lavoie O, Watters V, Hussein S, Adjibade P, Mazroui R. The nuclear isoforms of the Fragile X Mental Retardation RNA-binding Protein associate with genomic DNA bridges. Mol Biol Cell;2023 (Mar 8):mbcE22050157.

The Fragile X Mental Retardation Protein (FMRP) is a canonical RNA-binding protein whose absence in humans leads to the development of the Fragile X Syndrome characterized by multiple phenotypes including neurodevelopmental disorders, intellectual disability, autism, and macroorchidism. The primary transcripts of the FMR1 gene undergo extensive alternative splicing processes, and multiple protein isoforms are produced. The predominantly cytoplasmic isoforms are translational regulators, while the roles of the nuclear ones have been neglected. In this study, we discovered that nuclear FMRP isoforms specifically associate with DNA bridges, aberrant genomic structures that form during mitosis and whose accumulation can drive genome instability by inducing DNA damage. Further localisation studies showed that a subset of FMRP-positive bridges contain proteins that have been shown to associate with specific DNA bridges known as ultrafine DNA bridges (UFBs), and surprisingly are RNA positive. Significantly, the depletion of nuclear FMRP isoforms promotes the accumulation of DNA bridges, correlating with the accumulation of DNA damages and cell death, unveiling an important function of these neglected isoforms.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lin CW, Ellegood J, Tamada K, Miura I, Konda M, Takeshita K, Atarashi K, Lerch JP, Wakana S, McHugh TJ, Takumi T. An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development. Mol Psychiatry;2023 (Mar 7)

The BTBR T(+)Itpr3(tf)/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.

Lien vers le texte intégral (Open Access ou abonnement)

10. Liu S, Tang F, Dou H, Zhang W. The relationship between autistic traits and empathy in adolescents: An ERP study. Neurosci Lett;2023 (Mar 8);802:137173.

Based on the mind-blindness hypothesis, a large number of studies have shown that individuals with autism-spectrum disorder (ASD) and autistic traits have empathy deficits. However, the recent double empathy theory contradicts the mind-blindness hypothesis and suggests that individuals with ASD and autistic traits do not necessarily lack empathy. Thus, the presence of empathy deficits in individuals with ASD and autistic traits is still controversial. We recruited 56 adolescents (28 high autistic traits, 28 low autistic traits, 14-17 years old) in this study to explore the relationship between empathy and autistic traits. The study participants were required to undertake the pain empathy task, during which the electroencephalograph (EEG) activities were recorded. Our results show that empathy was negatively associated with autistic traits at the questionnaire, behavioral, and EEG levels. Our results also suggested that empathy deficits in adolescents with autistic traits may be manifested mainly in the late stages of cognitive control processing.

Lien vers le texte intégral (Open Access ou abonnement)

11. Machado S, Lucas Lima J, Imperatori C, Souza de Sá Filho A. Commentary: Is Torasemide a Potential Agent in the Treatment of Autism?. Alpha Psychiatry;2023 (Jan);24(1):32-33.

Lien vers le texte intégral (Open Access ou abonnement)

12. Okada M, Nagayama Y, Saiki H, Ito K, Yatsuga S, Nagamitsu S. Selenium deficiency and scurvy due to an imbalanced diet of snacks and lacto-fermenting drinks: a case report of a 7-year-old boy with autism spectrum disorder. BMC Nutr;2023 (Mar 8);9(1):41.

BACKGROUND: There have been reports of isolated trace elements or vitamin deficiencies due to imbalanced diets, but no cases of selenium deficiency combined with scurvy have been reported. CASE PRESENTATION: A 7 year-old boy diagnosed with autistic spectrum disorder and mild psychomotor retardation, started an imbalanced diet including specific snacks and lacto-fermenting drinks from 5 years of age. Gingival hemorrhage and perioral erosions occurred at 6 years and 8 months of age, and he was referred to our hospital at 7 years of age. Slight tachycardia was found. Serum vitamin C level was 1.1 µg/dL (reference range (rr): 5-17.5 µg/dL), and selenium level was 2.8 µg/dL (rr: 7.7-14.8 µg/dL). He was diagnosed with both selenium deficiency and scurvy. Multivitamins and sodium selenate were administered for 12 days during admission, and symptoms of selenium deficiency and scurvy improved. After discharge, symptoms abated following the administration of multivitamins and regular administration of sodium selenate every 3 months. CONCLUSIONS: We report a complicated case of both selenium deficiency and scurvy due to an imbalanced diet of snacks and lacto-fermenting drinks in a 7-year-old boy with autism spectrum disorder. In patients with imbalanced diet, regular blood tests including trace elements and vitamins are necessary.

Lien vers le texte intégral (Open Access ou abonnement)

13. Olusanya BO, Gulati S, Newton CRJ. The Nurturing Care Framework and Children With Developmental Disabilities in LMICs. Pediatrics;2023 (Mar 7)

Lien vers le texte intégral (Open Access ou abonnement)

14. Straub D, Schmitt LM, Boggs AE, Horn PS, Dominick KC, Gross C, Erickson CA. A sensitive and reproducible qRT-PCR assay detects physiological relevant trace levels of FMR1 mRNA in individuals with Fragile X syndrome. Sci Rep;2023 (Mar 7);13(1):3808.

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS is caused by a trinucleotide repeat expansion in the 5′ untranslated region of the FMR1 gene, which leads to gene methylation, transcriptional silencing, and lack of expression of Fragile X Messenger Riboprotein (FMRP). Currently available FXS therapies are inefficient, and the disease severity is highly variable, making it difficult to predict disease trajectory and treatment response. We and others have recently shown that a subset of full-mutation, fully-methylated (FM-FM) males with FXS express low amounts of FMRP which could contribute to phenotypic variability. To better understand the underlying mechanisms, we developed a sensitive qRT-PCR assay to detect FMR1 mRNA in blood. This assay reproducibly detects trace amounts of FMR1 mRNA in a subset of FM-FM males, suggesting that current Southern Blot and PCR determination of FM-FM status is not always associated with complete transcriptional silencing. The functional relevance of trace-level FMR1 mRNA is confirmed by showing a positive correlation with cognitive function; however, phenotypic variability is not fully explained by FMR1 expression. These results corroborate the need for better molecular assays for FXS diagnosis and encourage studies to elucidate the factors contributing to the phenotypic variability of FXS.

Lien vers le texte intégral (Open Access ou abonnement)

15. Taylor TN, Bridges CS, Nordstrom LA, Hanson DS, Gerow FT, Smith BG. Early Complications After Posterior Spinal Fusion in Patients With Rett Syndrome. J Pediatr Orthop;2023 (Mar 6)

BACKGROUND: Neuromuscular scoliosis in Rett syndrome (RS) is common, progressive, and often requires posterior spinal fusion (PSF). While PSF is associated with improved overall outcomes, there is a paucity of information describing complications. We aimed to report the postoperative complications, readmissions, and reoperations for patients with RS undergoing PSF. METHODS: Female pediatric patients with RS treated by PSF with segmental instrumentation, with or without concurrent pelvis fixation, during January 2012 to August 2022 were included. Preoperative patient characteristics, intraoperative data (estimated blood loss, cell saver, packed red blood cells transfused), postoperative complications according to the Modified Clavien-Dindo-Sink classification within 90 days, unplanned readmissions within 30 days, and unplanned reoperations within 90 days were recorded. RESULTS: A total of 25 females were included. The mean (SD) age at surgery was 12.9 (1.8) years and the mean follow-up of 38.6 (24.9) months. The mean preoperative major coronal curve was 79 degrees (23 degrees) which decreased to 32 degrees (15 degrees) by the last follow-up (P<0.001). The median estimated blood loss was 600 mL and length of stay was 7 days. There were 81 total postoperative complications (3.2 complications/patient). Eight (32%) had grade IVa complications (disseminated intravascular coagulopathy, hypotensive shock, respiratory failure, chronic urosepsis). Five (20%) patients experienced seizures, 48% had pulmonary complications, and 56% had gastrointestinal complications. There were 3 readmissions (12%) within 30 days for pneumonia and 2 (8%) reoperations (an incision and drainage and C2-T2 fusion for significant kyphosis) within 90 days. One patient also had their fusion extended to the pelvis 1 year later. There were more nonambulatory patients in the group fused to the pelvis, but otherwise no differences between those fused and unfused to the pelvis. CONCLUSIONS: This is the largest review of early postoperative complications for patients with RS who underwent PSF. PSF effectively reduced the major coronal curve, but surgeons and families should be aware of a high postoperative seizure and respiratory complication rate, as well as 8% having reoperations within 90 days and 12% being readmitted within 30 days. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Lien vers le texte intégral (Open Access ou abonnement)

16. Tsuji M, Mukai T, Sato Y, Azuma Y, Yamamoto S, Cayetanot F, Bodineau L, Onoda A, Nagamura-Inoue T, Coq JO. Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight. Sci Rep;2023 (Mar 7);13(1):3841.

Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attention-deficit/hyperactive disorder and autism spectrum disorder, as well as cerebral palsy, for which no prophylactic measure exists. Neuroinflammation in fetuses and neonates plays a major pathogenic role in NDDs. Meanwhile, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) exhibit immunomodulatory properties. Therefore, we hypothesized that systemic administration of UC-MSCs in the early postnatal period may attenuate neuroinflammation and thereby prevent the emergence of NDDs. The LBW pups born to dams subjected to mild intrauterine hypoperfusion exhibited a significantly lesser decrease in the monosynaptic response with increased frequency of stimulation to the spinal cord preparation from postnatal day 4 (P4) to P6, suggesting hyperexcitability, which was improved by intravenous administration of human UC-MSCs (1 × 10(5) cells) on P1. Three-chamber sociability tests at adolescence revealed that only LBW males exhibited disturbed sociability, which tended to be ameliorated by UC-MSC treatment. Other parameters, including those determined via open-field tests, were not significantly improved by UC-MSC treatment. Serum or cerebrospinal fluid levels of pro-inflammatory cytokines were not elevated in the LBW pups, and UC-MSC treatment did not decrease these levels. In conclusion, although UC-MSC treatment prevents hyperexcitability in LBW pups, beneficial effects for NDDs are marginal.

Lien vers le texte intégral (Open Access ou abonnement)

17. Yuan B, Wang M, Wu X, Cheng P, Zhang R, Yu S, Zhang J, Du Y, Wang X, Qiu Z. Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism. Neurosci Bull;2023 (Mar 7)

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

18. Zhang H, Tang X, Feng C, Gao Y, Qi H, Junzhang, Zhang X, Zheng Q, Lin J, Liu X, Shen L. The use of data independent acquisition based proteomic analysis and machine learning to reveal potential biomarkers for autism spectrum disorder. J Proteomics;2023 (Mar 8):104872.

Autism spectrum disorder (ASD) is a complex neurological developmental disorder in children, and is associated with social isolation and restricted interests. The etiology of this disorder is still unknown. There is neither any confirmed laboratory test nor any effective therapeutic strategy to diagnose or cure it. We performed data independent acquisition (DIA) and multiple reaction monitoring (MRM) analysis of plasma from children with ASD and controls. The result showed that 45 differentially expressed proteins (DEPs) were identified between autistic subjects and controls. Among these, only one DEP was down-regulated in ASD; other DEPs were up-regulated in ASD children’s plasma. These proteins are found associated with complement and coagulation cascades, vitamin digestion and absorption, cholesterol metabolism, platelet degranulation, selenium micronutrient network, extracellular matrix organization and inflammatory pathway, which have been reported to be related to ASD. After MRM verification, five key proteins in complement pathway (PLG, SERPINC1, and A2M) and inflammatory pathway (CD5L, ATRN, SERPINC1, and A2M) were confirmed to be significantly up-regulated in ASD group. Through the screening of machine learning model and MRM verification, we found that two proteins (biotinidase and carbonic anhydrase 1) can be used as early diagnostic markers of ASD (AUC = 0.8, p = 0.0001). SIGNIFICANCE: ASD is the fastest growing neurodevelopmental disorder in the world and has become a major public health problem worldwide. Its prevalence has been steadily increasing, with a global prevalence rate of 1%. Early diagnosis and intervention can achieve better prognosis. In this study, data independent acquisition (DIA) and multiple reaction monitoring (MRM) analysis was applied to analyze the plasma proteome of ASD patients (31 (±5) months old), and 378 proteins were quantified. 45 differentially expressed proteins (DEPs) were identified between the ASD group and the control group. They mainly were associated with platelet degranulation, ECM proteoglycar, complement and coagulation cascades, selenium micronutrient network, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), cholesterol metabolism, vitamin metabolism, and inflammatory pathway. Through the integrated machine learning methods and the MRM verification of independent samples, it is considered that biotinidase and carbon anhydrase 1 have the potential to become biomarkers for the early diagnosis of ASD. These results complement proteomics database of the ASD patients, broaden our understanding of ASD, and provide a panel of biomarkers for the early diagnosis of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

19. Zhao Y, Luo Y, Zhang R, Zheng X. Direct and indirect costs for families of children with autism spectrum disorder in China. Autism;2023 (Mar 7):13623613231158862.

This is the first comprehensive national study to explore the direct and indirect costs for families of children with autism spectrum disorder in China. The increasing prevalence of autism spectrum disorder highlights a growing need for resources to provide care for families of children with autism spectrum disorder. The medical and nonmedical costs and parents’ productivity loss have caused a serious burden on their families. Our objective is to estimate the direct and indirect costs for the families of children with autism spectrum disorder in China. The target population was parents of children with autism spectrum disorder. We analyzed the costs using cross-sectional data from a Chinese national family survey with children aged 2-6 years (N = 3236) who were clinically diagnosed with autism spectrum disorder. Family data from 30 provinces in China were obtained. Cost items included direct medical costs, direct nonmedical costs, and indirect costs. In this study, we found that the largest part of family costs for autism spectrum disorder are nonmedical costs and productivity loss. Autism spectrum disorder has imposed a huge economic burden on parents having children with autism spectrum disorder in China, who need more support than the current health care system provides.

Lien vers le texte intégral (Open Access ou abonnement)