1. Abdel-Haq M, Ojha SK, Hamoudi W, Kumar A, Tripathi MK, Khaliulin I, Domb AJ, Amal H. Effects of extended-release 7-nitroindazole gel formulation treatment on the behavior of Shank3 mouse model of autism. Nitric oxide : biology and chemistry. 2023.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral deficits such as abnormalities in communication, social interaction, anxiety, and repetitive behavior. We have recently shown that the Shank3 mutation in mice representing a model of ASD causes excessive nitric oxide (NO) levels and aberrant protein S-nitrosylation. Further, 10-day daily injections of 7-NI, a neuronal nitric oxide synthase inhibitor, into Shank3(Δ4-22) and Cntnap2((-/-)) mutant mice (models of ASD) at a dose of 80mg/kg reversed the manifestations of ASD phenotype. In this study, we proposed an extended release of 7-NI using novel drug system. Importantly, unlike the intraperitoneal injections, our new preparation of poly (sebacic acid-co-ricinoleic acid) (PSARA) gel containing 7-NI was injected subcutaneously into the mutant mice only once. The animals underwent behavioral testing starting from day 3 post-injection. It should be noted that the developed PSARA gel formulation allowed a slow release of 7-NI maintaining the plasma level of the drug at ∼45 μg/ml/day. Further, we observed improved cognitive memory and social interaction and reduced anxiety-like behavior in Shank3 mutant mice. This was accompanied by a reduction in 3-nitrotyrosine levels (an indicator of nitrative/nitrosative stress) in plasma. Overall, we suggest that our single-dose formulation of PSARA gel is very efficient in rendering a therapeutic effect of 7-NI for at least 10 days. This approach may provide in the future a rational design of an effective ASD treatment using 7-NI and its clinical translation.

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2. Buch AM, Liston C. Gene-brain-behavior mechanisms underlying autism spectrum disorder: implications for precision psychiatry. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2023.

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3. Macdonald O, Green A, Walker A, Curtis H, Croker R, Brown A, Butler-Cole B, Andrews C, Massey J, Inglesby P, Morton C, Fisher L, Morley J, Mehrkar A, Bacon S, Davy S, Evans D, Dillingham I, Ward T, Hulme W, Bates C, Cockburn J, Parry J, Hester F, Harper S, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Parkes N, Wood I, Goldacre B, Mackenna B. Impact of the COVID-19 pandemic on antipsychotic prescribing in individuals with autism, dementia, learning disability, serious mental illness or living in a care home: a federated analysis of 59 million patients’ primary care records in situ using OpenSAFELY. BMJ mental health. 2023; 26(1).

BACKGROUND: The COVID-19 pandemic affected how care was delivered to vulnerable patients, such as those with dementia or learning disability. OBJECTIVE: To explore whether this affected antipsychotic prescribing in at-risk populations. METHODS: With the approval of NHS England, we completed a retrospective cohort study, using the OpenSAFELY platform to explore primary care data of 59 million patients. We identified patients in five at-risk groups: autism, dementia, learning disability, serious mental illness and care home residents. We calculated the monthly prevalence of antipsychotic prescribing in these groups, as well as the incidence of new prescriptions in each month. FINDINGS: The average monthly rate of antipsychotic prescribing increased in dementia from 82.75 patients prescribed an antipsychotic per 1000 patients (95% CI 82.30 to 83.19) in January-March 2019 to 90.1 (95% CI 89.68 to 90.60) in October-December 2021 and from 154.61 (95% CI 153.79 to 155.43) to 166.95 (95% CI 166.23 to 167.67) in care homes. There were notable spikes in the rate of new prescriptions issued to patients with dementia and in care homes. In learning disability and autism groups, the rate of prescribing per 1000 decreased from 122.97 (95% CI 122.29 to 123.66) to 119.29 (95% CI 118.68 to 119.91) and from 54.91 (95% CI 54.52 to 55.29) to 51.04 (95% CI 50.74 to 51.35), respectively. CONCLUSION AND IMPLICATIONS: We observed a spike in antipsychotic prescribing in the dementia and care home groups, which correlated with lockdowns and was likely due to prescribing of antipsychotics for palliative care. We observed gradual increases in antipsychotic use in dementia and care home patients and decreases in their use in patients with learning disability or autism.

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4. Newbutt N, Glaser N, Francois MS, Schmidt M, Cobb S. How are Autistic People Involved in the Design of Extended Reality Technologies? A Systematic Literature Review. Journal of autism and developmental disorders. 2023.

The primary aim of this systematic review is to investigate the inclusion of autistic individuals in the design process of immersive technologies. This study follows the preferred reporting items for systematic reviews and meta-analyses standards for systematic literature reviews. To ensure the research questions and subsequent stages of the review incorporate pertinent parameters, the problem, interest, context framework has also been employed. Findings highlight that, while early proponents of immersive technology emphasized the importance of user involvement in design of new technology, immaturity of the technology often limited the implementation of direct user input to the design process. Nonetheless, analysis of the literature published between 2002-2022 identified 20 studies in which substantial influence of autistic individuals and stakeholders was found in the design process of immersive technologies. The roles of autistic individuals varied from active co-designers and co-creators to essential contributors in refining prototypes and providing critical feedback, ensuring the final products align with their needs and preferences. Results underscore the need to align research and design of immersive technologies more closely with the priorities and preferences of autistic individuals. Further is needed regarding actively involving autistic individuals in the design and implementation of immersive technology applications. On this basis, we maintain that more inclusive and effective deployment of immersive technologies is needed in order to ensure that resultant technologies are fit for purpose and address the actual needs of the autistic community.

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5. Nickel K, Menke M, Endres D, Runge K, Tucci S, Schumann A, Domschke K, Tebartz van Elst L, Maier S. Altered markers of mitochondrial function in adults with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2023.

Previous research suggests potential mitochondrial dysfunction and changes in fatty acid metabolism in a subgroup of individuals with autism spectrum disorder (ASD), indicated by higher lactate, pyruvate levels, and mitochondrial disorder prevalence. This study aimed to further investigate potential mitochondrial dysfunction in ASD by assessing blood metabolite levels linked to mitochondrial metabolism. Blood levels of creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate, pyruvate, free and total carnitine, as well as acylcarnitines were obtained in 73 adults with ASD (47 males, 26 females) and compared with those of 71 neurotypical controls (NTC) (44 males, 27 females). Correlations between blood parameters and psychometric ASD symptom scores were also explored. Lower CK (p(corr)  = 0.045) levels were found exclusively in males with ASD compared to NTC, with no such variation in females. ALT and AST levels did not differ significantly between both groups. After correction for antipsychotic and antidepressant medication, CK remained significant. ASD participants had lower serum lactate levels (p(corr)  = 0.036) compared to NTC, but pyruvate and carnitine concentrations showed no significant difference. ASD subjects had significantly increased levels of certain acylcarnitines, with a decrease in tetradecadienoyl-carnitine (C14:2), and certain acylcarnitines correlated significantly with autistic symptom scores. We found reduced serum lactate levels in ASD, in contrast to previous studies suggesting elevated lactate or pyruvate. This difference may reflect the focus of our study on high-functioning adults with ASD, who are likely to have fewer secondary genetic conditions associated with mitochondrial dysfunction. Our findings of significantly altered acylcarnitine levels in ASD support the hypothesis of altered fatty acid metabolism in a subset of ASD patients.

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6. Ricciardelli P, Pintori N. Effect of race on Gaze Cueing in adults with high and low autistic traits. BMC psychology. 2023; 11(1): 275.

BACKGROUND: Observing the direction of gaze of another person leads to shifting of attention in the same direction (gaze-cueing effect – GCE), a social-cognitive ability known as joint or social attention. Racial attitudes can influence the magnitude of GCE since it has been shown that White people showing a strong race ingroup preference follow the gaze only of White, and not Black, faces. Individuals with high autistic traits have difficulties in social-cognitive abilities that can disrupt the learning of socially shared racial attitudes. Our aim was to investigate in White Italian adults whether individuals with higher autistic traits (measured by the Autism Spectrum Quotient) show reduced implicit racial bias (measured by the Implicit Association Test) and if this bias would lead to differences in the gaze cueing effect (GCE) triggered by gaze direction of faces of different races (measured by the Gaze Cueing Task). METHODS: In an online study, participants (N = 165; 132 females; Mean age = 22.9; SD = 4.76) filled in the Autism Spectrum Quotient (AQ) questionnaire, then performed a Gaze Cueing Task, followed and by an Implicit Association Test. RESULTS: Linear regression and linear mixed model analyses showed in the IAT task the presence of the same implicit ingroup bias for all participants, which was not predicted by the AQ score, while in the Gaze Cueing Task the GCE differed depending on the AQ score of the participants. Specifically, participants with low-medium, medium, and medium-high autistic traits (AQ = -1SD; AQ = mean; AQ =  + 1SD respectively) presented the GCE for both ingroup and outgroup cueing faces, whereas participants with high autistic traits (AQ =  + 2SD) only for ingroup faces. CONCLUSIONS: In White Italian adults the presence of an implicit ingroup bias seems to influence the GCE, but it is not always true that the individuals showing an implicit ingroup bias do not orient their attention in the direction of gaze of the outgroup individuals. Instead, the GCE seems to be modulated by the level of autistic traits. That is, individuals with higher autistic traits seem to prioritize joint attention with only their ingroup members.

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7. Risner-Bauman A, Robbins MR. Nonverbal Patient with Autistic Spectrum Disorder Presents for an Initial Dental Visit. Dental clinics of North America. 2023; 67(4): 565-8.

Autistic spectrum disorder (ASD) can be characterized by communication and social interaction difficulties, focused or repetitive behaviors, and an apathetic demeanor. The understanding level of an individual who cannot communicate cannot be assessed; therefore, we cannot assume the level of understanding of some individuals with ASD. Unfortunately, general anesthesia (GA) is oftentimes used for individuals with ASD due to their inability to cooperate, possible aggressive behaviors, and inadvertent movements, without first trying less-restrictive techniques. Teaching dentists how to develop and execute management plans without GA can increase access to dental care for this population and improve their overall health.

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8. Ruggieri V. [Autism. Pharmacological treatment]. Medicina. 2023; 83 Suppl 4: 46-51.

Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroaggression crises. Serotonin reuptake inhibitors, to decrease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As specific entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism..

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9. Wright DC, Baluyot ML, Carmichael J, Darmanian A, Jose N, Ngo C, Heaps LS, Yendle A, Holman K, Ziso S, Khan F, Masi A, Silove N, Eapen V. Saliva DNA: An alternative biospecimen for single nucleotide polymorphism chromosomal microarray analysis in autism. American journal of medical genetics Part A. 2023.

Chromosomal microarray analysis (CMA) is typically performed for investigation of autism using blood DNA. However, blood collection poses significant challenges for autistic children with repetitive behaviors and sensory and communication issues, often necessitating physical restraint or sedation. Noninvasive saliva collection offers an alternative, however, no published studies to date have evaluated saliva DNA for CMA in autism. Furthermore, previous reports suggest that saliva is suboptimal for detecting copy number variation. We therefore aimed to evaluate saliva DNA for single nucleotide polymorphism (SNP) CMA in autistic children. Saliva DNA from 48 probands and parents (n = 133) was obtained with a mean concentration of 141.7 ng/μL. SNP CMA was successful in 131/133 (98.5%) patients from which we correlated the size and accuracy of a copy number variant(s) called between a proband and carrier parent, and for a subgroup (n = 17 probands) who had a previous CMA using blood sample. There were no discordant copy number variant results between the proband and carrier parent, or the subgroup, however, there was an acceptable mean size difference of 0.009 and 0.07 Mb, respectively. Our findings demonstrate that saliva DNA can be an alternative for SNP CMA in autism, which avoids blood collection with significant implications for clinical practice guidelines.

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