1. Binder MS, Bordey A. The novel somatosensory nose-poke adapted paradigm (SNAP) is an effective tool to assess differences in tactile sensory preferences in autistic-like mice. eNeuro;2023 (Aug 18)

One of the most prevalent deficits in autism spectrum disorder (ASD) are sensitivities to sensory stimuli. Despite the prevalence of sensory deficits in autism, there are few paradigms capable of easily assessing sensory behaviors in ASD-like mouse models. We addressed this need by creating the Somatosensory Nose-poke Adapted Paradigm (SNAP), which consists of an elevated platform with 6 holes in the center, half of which are lined with sandpaper and half are smooth, requiring mice to use their whiskers to sense the texture. The SNAP paradigm assesses tactile sensory preferences as well as stereotypy, anxiety, and locomotion. We used two wildtype (neurotypical) mouse strains, C57BL/6J (C57) inbred and CD-1 outbred mice, and two ASD mouse models, BTBR (a model of idiopathic ASD) and Cntnap2(-/-) mice (a model of syndromic ASD). We found that both ASD models produced more nose pokes into the rough condition than the smooth condition, suggesting an increased preference for complex tactile stimulation when compared to the neurotypical groups, wherein no differences were observed. Furthermore, we found increased stereotypy and time spent in the center, suggestive of decreased anxiety, only for BTBR mice compared to the other mouse strains. Overall, SNAP is an easy to implement task to assess the degree of preference for complex tactile stimulation in ASD mouse models that can be further modified to exclude possible confounding effects of novelty or anxiety on the sensory preferences.Significance StatementDespite sensory deficits occurring in 90% of individuals with ASD, there are few behavioral sensory tasks available. To address this need, we developed a tactile sensory task, called the Somatosensory Nose-poke Adapted Paradigm (SNAP) that harnesses innate behavior, is easy to implement, and is not memory dependent. We assessed two neurotypical mouse strains: C57 and CD-1 mice, and two ASD mouse models: BTBR and Cntnap2(-/-) mice. Both ASD models displayed preferences for rough textures and inter-strain differences in stereotypy, anxiety, and locomotion. SNAP is thus an easy to implement test to assess differences in tactile sensory preferences in ASD mouse models.

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2. Burns J, Phung R, McNeill S, Hanlon-Dearman A, Ricci MF. Comorbidities Affecting Children with Autism Spectrum Disorder: A Retrospective Chart Review. Children (Basel);2023 (Aug 19);10(8)

Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction/communication, restricted interests, and repetitive behaviors. Recent discussions have emerged worldwide regarding the heterogeneity around presentation/etiology and comorbidities. This study aimed to determine the frequency and characteristics of comorbidities among children diagnosed with ASD in Manitoba and to evaluate differences in presentation between those with and without medical comorbidities. We conducted a retrospective chart review of >1900 electronic charts at the only publicly funded referral site for children ≤6 years requiring evaluation for ASD in Manitoba. All children aged 0-6 years diagnosed with ASD at this site between May 2016 and September 2021 were identified. χ(2) and t-tests were used to compare groups. Of the total of 1858 children identified, 1452 (78.1%) were boys, 251 (13.5%) were prematurely born, and 539 (29.0%) had ≥1 medical comorbidity. Global developmental delay (GDD) was diagnosed in 428 (23.0%). The age of referral and diagnosis did not differ between groups. Comorbidities were more common among premature children (16.0% vs. 12.5%, p: 0.005) and children with comorbid GDD (34.9% vs. 18.2%, p < 0.001). Neurological comorbidities were most common (37.1%). No sex difference in the overall presence of comorbidities was found (boys = 77.1% vs. 78.5%, p: 0.518); however, girls had a higher incidence of neurological comorbidities, e.g., cerebral palsy, seizures, hypotonia (14.8% vs. 9.64%, p: 0.009), as well as genetic comorbidities (4.92% vs. 2.75%, p: 0.04). The high rates of associated neurological conditions, GDD, and prematurity add heterogeneity to this group leading to potential difficulties with prognosis and service allocation. Primary vs. secondary ASD can be a way of separating individuals based on relevant medical comorbidities.

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3. Lee BK, Schendel DE, Shea LL. Big data in autism research: Methodological challenges and solutions. Autism Res;2023 (Aug 19)

While the concept of big data has emerged over the past decade as a hot topic in nearly all areas of scientific inquiry, it has rarely been discussed in the context of autism research. In this commentary we describe aspects of big data that are relevant to autism research and methodological issues such as confounding and data error that can hamper scientific investigation. Although big data studies can have transformative impact, bigger is not always better, and big data require the same methodological considerations and interdisciplinary collaboration as « small data » to extract useful scientific insight.

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4. Lin HH, Jung CR, Lin CY, Chang YC, Hsieh CY, Hsu PC, Chuang BR, Hwang BF. Prenatal and postnatal exposure to heavy metals in PM(2.5) and autism spectrum disorder. Environ Res;2023 (Aug 17);237(Pt 1):116874.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders, and its incidence is increasing over time. Although several environmental factors have been suspected to be risk factors for ASD, studies on the effects of airborne heavy metals on newly developed ASD are still limited. We conducted a large birth cohort study of 168,062 live term births in Taichung during 2004-2011 to assess the association of heavy metals in particulate matter with an aerodynamic diameter less than 2.5 μm (PM(2.5)) with ASD, and identify sensitive time windows during prenatal and postnatal periods. Heavy metals, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in PM(2.5), were estimated using the Weather Research and Forecasting/Chem (WRF/Chem), inserted from the top 75 emission sources for the module. The association between childhood ASD and 4 metals were analyzed from pregnancy to 9 months after birth. The Cox proportional hazard model with a distributed lag nonlinear model (DLNM) was used to estimate the association between heavy metals in PM(2.5) and ASD. We identified 666 incident ASD cases in 168,062 participants. A positive association between Hg and ASD was found at 9 months after birth (Hazard Ratio: 1.63; 95% CI: 1.13-2.36). According to the DLNM, there was an increased risk of exposure to Hg during 10-25 weeks after birth, and decreased risk of exposure to Hg during gestational weeks 4-6. Exposure to As and Hg on the risk of ASD were significantly stronger in low birth weight infants (<2500 g) than in those of birth weight ≥2500 g during postnatal period. Postnatal exposure to Hg in PM(2.5) may associate with increased ASD incidence. Infants with low birth weight and exposure to As and Hg in PM(2.5) are more likely to develop ASD.

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5. Lowther C, Valkanas E, Giordano JL, Wang HZ, Currall BB, O’Keefe K, Pierce-Hoffman E, Kurtas NE, Whelan CW, Hao SP, Weisburd B, Jalili V, Fu J, Wong I, Collins RL, Zhao X, Austin-Tse CA, Evangelista E, Lemire G, Aggarwal VS, Lucente D, Gauthier LD, Tolonen C, Sahakian N, Stevens C, An JY, Dong S, Norton ME, MacKenzie TC, Devlin B, Gilmore K, Powell BC, Brandt A, Vetrini F, DiVito M, Sanders SJ, MacArthur DG, Hodge JC, O’Donnell-Luria A, Rehm HL, Vora NL, Levy B, Brand H, Wapner RJ, Talkowski ME. Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies. Am J Hum Genet;2023 (Aug 16)

Short-read genome sequencing (GS) holds the promise of becoming the primary diagnostic approach for the assessment of autism spectrum disorder (ASD) and fetal structural anomalies (FSAs). However, few studies have comprehensively evaluated its performance against current standard-of-care diagnostic tests: karyotype, chromosomal microarray (CMA), and exome sequencing (ES). To assess the clinical utility of GS, we compared its diagnostic yield against these three tests in 1,612 quartet families including an individual with ASD and in 295 prenatal families. Our GS analytic framework identified a diagnostic variant in 7.8% of ASD probands, almost 2-fold more than CMA (4.3%) and 3-fold more than ES (2.7%). However, when we systematically captured copy-number variants (CNVs) from the exome data, the diagnostic yield of ES (7.4%) was brought much closer to, but did not surpass, GS. Similarly, we estimated that GS could achieve an overall diagnostic yield of 46.1% in unselected FSAs, representing a 17.2% increased yield over karyotype, 14.1% over CMA, and 4.1% over ES with CNV calling or 36.1% increase without CNV discovery. Overall, GS provided an added diagnostic yield of 0.4% and 0.8% beyond the combination of all three standard-of-care tests in ASD and FSAs, respectively. This corresponded to nine GS unique diagnostic variants, including sequence variants in exons not captured by ES, structural variants (SVs) inaccessible to existing standard-of-care tests, and SVs where the resolution of GS changed variant classification. Overall, this large-scale evaluation demonstrated that GS significantly outperforms each individual standard-of-care test while also outperforming the combination of all three tests, thus warranting consideration as the first-tier diagnostic approach for the assessment of ASD and FSAs.

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6. Mazzucchelli TG, Tonge BJ, Brereton AV, Wade C, Baird-Bate K, Dawe S. The national disability insurance scheme and parenting support for families of children with developmental disability: A need for policy reform. Aust N Z J Psychiatry;2023 (Aug 19):48674231192369.

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7. Saadat M, Taherian AA, Aldaghi MR, Raise-Abdullahi P, Sameni HR, Vafaei AA. Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. Brain Behav;2023 (Aug 18):e3224.

BACKGROUND: Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid. METHODS: Pregnant rats received VPA (600 mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200 mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus-maze, hot-plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay. RESULTS: Prenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA-induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus. CONCLUSION: The findings of this study suggest that postnatal administration of PF can prevent VPA-induced ASD-like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

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8. van den Boogert F, Sizoo B, Bouman YHA, Hoogendijk WJG, Roza SJ. Sensory Processing and Alcohol Use in Adults with Autism Spectrum Disorder. Alcohol;2023 (Aug 19)

The association between substance use and autism spectrum disorder (ASD) is complex. Although sensory processing difficulties are highly prevalent in individuals with ASD, data on the association between sensory processing and substance use in ASD are limited. This study aimed to investigate the association between sensory processing patterns and alcohol use in adults with ASD. Kruskal-Wallis Tests were performed on questionnaire data (Adolescent/Adult Sensory Profile and Alcohol Use Disorders Identification Test – Consumption) of 101 adults with ASD. Sensory processing difficulties are associated with alcohol use in adults with ASD. Differences in sensory processing between alcohol-based subgroups vary per specific sensory processing pattern: drinkers reported 6.5 to 8 points higher levels of low registration (χ(2)(2)=12.408,p=.002,99%CI[.002,.002]), non-hazardous drinkers reported 9 points higher levels of sensory sensitivity (χ(2)(2)=6.868,p=.031,99%CI[.031,.032]) and hazardous drinkers reported 7.5 points higher levels of sensory seeking (χ(2)(2)=6.698,p=.034,99%CI[.034,.035]), all in comparison with non-drinkers on scales ranging from 15 to 75. Our proof-of-concept study indicates that vulnerability in some individuals with ASD for substance use disorders might be explained by sensory processing difficulties. Whether alcohol is used as ‘self-medication’ or is associated with other neurobiological vulnerabilities needs further investigation in larger follow-up studies.

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9. Veneruso I, Ranieri A, Falcone N, Tripodi L, Scarano C, La Monica I, Pastore L, Lombardo B, D’Argenio V. The Potential Usefulness of the Expanded Carrier Screening to Identify Hereditary Genetic Diseases: A Case Report from Real-World Data. Genes (Basel);2023 (Aug 19);14(8)

Expanded carrier screening (ECS) means a comprehensive genetic analysis to evaluate an individual’s carrier status. ECS is becoming more frequently used, thanks to the availability of techniques such as next generation sequencing (NGS) and array comparative genomic hybridization (aCGH), allowing for extensive genome-scale analyses. Here, we report the case of a couple who underwent ECS for a case of autism spectrum disorder in the male partner family. aCGH and whole-exome sequencing (WES) were performed in the couple. aCGH analysis identified in the female partner two deletions involving genes associated to behavioral and neurodevelopment disorders. No clinically relevant alterations were identified in the husband. Interestingly, WES analysis identified in the male partner a pathogenic variant in the LPL gene that is emerging as a novel candidate gene for autism. This case shows that ECS may be useful in clinical contexts, especially when both the partners are analyzed before conception, thus allowing the estimation of their risk to transmit an inherited condition. On the other side, there are several concerns related to possible incidental findings and difficult-to-interpret results. Once these limits are defined by the establishment of specific guidelines, ECS may have a greater diffusion.

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10. Yu X, Mostafijur Rahman M, Carter SA, Lin JC, Zhuang Z, Chow T, Lurmann FW, Kleeman MJ, Martinez MP, van Donkelaar A, Martin RV, Eckel SP, Chen Z, Levitt P, Schwartz J, Hackman D, Chen JC, McConnell R, Xiang AH. Prenatal air pollution, maternal immune activation, and autism spectrum disorder. Environ Int;2023 (Aug 14);179:108148.

BACKGROUND: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM(2.5)) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children. OBJECTIVES: This study examined interactions between MIA-related conditions and prenatal PM(2.5) or major PM(2.5) components on ASD risk. METHODS: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM(2.5) and four PM(2.5) components, black carbon (BC), organic matter (OM), nitrate (NO(3)(-)), and sulfate (SO(4)(2-)), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates. RESULTS: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM(2.5) [1.07; 1.03-1.12 per interquartile (3.73 μg/m(3)) increase] and with all four PM(2.5) components. However, there were no interactions of each category of MIA-related conditions with PM(2.5) or its components on either multiplicative or additive scales. CONCLUSIONS: MIA-related conditions and pregnancy PM(2.5) were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM(2.5) exposure with ASD risk.

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