1. AMS AL, SAS AL, Awladthani BMS, SA AL, Al Alawi N, Al Salmani AA. Quality of life and coping strategies used by parents of children with autism spectrum disorder in Oman. Autism & developmental language impairments. 2022; 7: 23969415221142262.

OBJECTIVE: Raising a child with autism spectrum disorder (ASD) can have a significant impact on quality of life (QOL). This study was conducted to assess the QOL and coping strategies of parents of children with ASD in Oman. METHOD: This descriptive cross-sectional study was conducted at Al-Masarra psychiatric hospital. Telephone interviews were conducted with the parents of all children diagnosed with ASD and attending Al-Masarra Hospital between January 2018 and October 2021. Data were collected using the Ways of Coping Checklist-Revised and World Health Organization Quality of Life Assessment-Brief. RESULTS: A total of 304 parents participated in the study (response rate: 100%), of which 59.5% were female. The mean age of the parents and children with ASD was 40.4 ± 6.9 and 8.4 ± 2.3 years, respectively. Most children with ASD were male (78.3%) and entirely dependent upon their parents (18.1%). Seeking social support was the most common coping strategy (75.53 ± 13.99), while escape avoidance was the least common (51.78 ± 8.04). Most parents (48.7%) rated their QOL as good to very good, with acceptable scores in the psychological (70.92 ± 11.22) and social (73.27 ± 11.46) domains, borderline in the physical health domain (63.51 ± 7.77), and poor in the environmental domain (58.31 ± 11.00). CONCLUSIONS: Omani parents of children with ASD utilize various coping strategies, with coping skills considered a positive index for mental health in general. No significant differences were observed between Omani fathers and mothers in terms of QOL or coping strategies.

Lien vers le texte intégral (Open Access ou abonnement)

2. Arutiunian V, Arcara G, Buyanova I, Davydova E, Pereverzeva D, Sorokin A, Tyushkevich S, Mamokhina U, Danilina K, Dragoy O. Neuromagnetic 40 Hz Auditory Steady-State Response in the left auditory cortex is related to language comprehension in children with Autism Spectrum Disorder. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 122: 110690.

Language impairment is comorbid in most children with Autism Spectrum Disorder (ASD), but its neural mechanisms are still poorly understood. Some studies hypothesize that the atypical low-level sensory perception in the auditory cortex accounts for the abnormal language development in these children. One of the potential non-invasive measures of such low-level perception can be the cortical gamma-band oscillations registered with magnetoencephalography (MEG), and 40 Hz Auditory Steady-State Response (40 Hz ASSR) is a reliable paradigm for eliciting auditory gamma response. Although there is research in children with and without ASD using 40 Hz ASSR, nothing is known about the relationship between this auditory response in children with ASD and their language abilities measured directly in formal assessment. In the present study, we used MEG and individual brain models to investigate 40 Hz ASSR in primary-school-aged children with and without ASD. It was also used to assess how the strength of the auditory response is related to language abilities of children with ASD, their non-verbal IQ, and social functioning. A total of 40 children were included in the study. The results demonstrated that 40 Hz ASSR was reduced in the right auditory cortex in children with ASD when comparing them to typically developing controls. Importantly, our study provides the first evidence of the association between 40 Hz ASSR in the language-dominant left auditory cortex and language comprehension in children with ASD. This link was domain-specific because the other brain-behavior correlations were non-significant.

Lien vers le texte intégral (Open Access ou abonnement)

3. Bar Yehuda S, Bauminger-Zviely N. Social-Motor Coordination Between Peers: Joint Action Developmental Trajectories in ASD and TD. Journal of autism and developmental disorders. 2022.

Coordinating a physical movement in time and space with social and nonsocial partners to achieve a shared goal – « joint action » (JA) – characterizes many peer-engagement situations that pose challenges for individuals with autism spectrum disorder (ASD). This cross-sectional study examined development of JA capabilities comparing ASD versus typically developing (TD) groups in early childhood, preadolescence, and adolescence while performing mirroring and complementing JA tasks with social (peer) and nonsocial (computer) partners. Results indicated better motor coordination abilities on computerized tasks than in peer dyads, with larger peer-dyad deficits shown by the ASD group. Developmental growth in JA abilities emerged, but the ASD group lagged behind same-age peers with TD. Socio-motor interventions may offer new channels to facilitate peer engagement in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

4. Berent I, Theodore RM, Valencia E. Autism attenuates the perception of the mind-body divide. Proceedings of the National Academy of Sciences of the United States of America. 2022; 119(49): e2211628119.

People are intuitive Dualists-they tacitly consider the mind as ethereal, distinct from the body. Here we ask whether Dualism emerges naturally from the conflicting core principles that guide reasoning about objects, on the one hand, and about the minds of agents (theory of mind, ToM), on the other. To address this question, we explore Dualist reasoning in autism spectrum disorder (ASD)-a congenital disorder known to compromise ToM. If Dualism arises from ToM, then ASD ought to attenuate Dualism and promote Physicalism. In line with this prediction, Experiment 1 shows that, compared to controls, people with ASD are more likely to view psychological traits as embodied-as likely to manifest in a replica of one’s body. Experiment 2 demonstrates that, unlike controls, people with ASD do not consider thoughts as disembodied-as persistent in the afterlife (upon the body’s demise). If ASD promotes the perception of the psyche as embodied, and if (per Essentialism) embodiment suggests innateness, then ASD should further promote Nativism-this bias is shown in Experiment 3. Finally, Experiment 4 demonstrates that, in neurotypical (NT) participants, difficulties with ToM correlate with Physicalism. These results are the first to show that ASD attenuates Dualist reasoning and to link Dualism to ToM. These conclusions suggest that the mind-body distinction might be natural for people to entertain.

Lien vers le texte intégral (Open Access ou abonnement)

5. Boydston P, Redner R, Wold K. Examination of a Telehealth-Based Parent Training Program in Rural or Underserved Areas for Families Impacted by Autism. Behavior analysis in practice. 2022: 1-17.

Families of children with disabilities in rural areas face challenges accessing services due to location and lack of health-care providers. Telehealth-based intervention can mitigate challenges in accessing services. The present study sought to replicate and extend the telehealth-based, behavioral parent-training program, the Online and Applied System for Intervention Skills (OASIS), utilizing a multiple-baseline approach. Four parent-child dyads participated, with all children diagnosed with autism spectrum disorder. All dyads resided in rural/underserved areas. All dyads demonstrated an improvement on skill and knowledge assessments. The mean gain from baseline-to-treatment completion on skills assessments was 80.9% (range: 67.6%-95.5% points). The mean gain on knowledge assessments was 35.3% (range: 19.0%-49.0% points). It should be noted that parent skill gains were maintained over time. The present results provided additional empirical evidence demonstrating the effectiveness of OASIS, a telehealth-based parent-training model.

Lien vers le texte intégral (Open Access ou abonnement)

6. Buzzelli V, Carbone E, Manduca A, Schiavi S, Feo A, Perederiy JV, Ambert KH, Hausman M, Trezza V. Psilocybin mitigates the cognitive deficits observed in a rat model of Fragile X syndrome. Psychopharmacology. 2022.

RATIONALE: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and the leading monogenic cause of autism spectrum disorder (ASD). Serotonergic neurotransmission has a key role in the modulation of neuronal activity during development, and therefore, it has been hypothesized to be involved in ASD and co-occurring conditions including FXS. As serotonin is involved in synaptic remodeling and maturation, serotonergic insufficiency during childhood may have a compounding effect on brain patterning in neurodevelopmental disorders, manifesting as behavioral and emotional symptoms. Thus, compounds that stimulate serotonergic signaling such as psilocybin may offer promise as effective early interventions for developmental disorders such as ASD and FXS. OBJECTIVES: The aim of the present study was to test whether different protocols of psilocybin administration mitigate cognitive deficits displayed by the recently validated Fmr1-(Δ)exon 8 rat model of ASD, which is also a model of FXS. RESULTS: Our results revealed that systemic and oral administration of psilocybin microdoses normalizes the aberrant cognitive performance displayed by adolescent Fmr1-(Δ)exon 8 rats in the short-term version of the novel object recognition test-a measure of exploratory behavior, perception, and recognition. CONCLUSIONS: These data support the hypothesis that serotonin-modulating drugs such as psilocybin may be useful to ameliorate ASD-related cognitive deficits. Overall, this study provides evidence of the beneficial effects of different schedules of psilocybin treatment in mitigating the short-term cognitive deficit observed in a rat model of FXS.

Lien vers le texte intégral (Open Access ou abonnement)

7. Cao W, Li JH, Lin S, Xia QQ, Du YL, Yang Q, Ye YZ, Zeng LH, Li XY, Xu J, Luo JH. NMDA receptor hypofunction underlies deficits in parvalbumin interneurons and social behavior in neuroligin 3 R451C knockin mice. Cell reports. 2022; 41(10): 111771.

Neuroligins (NLs), a family of postsynaptic cell-adhesion molecules, have been associated with autism spectrum disorder. We have reported that dysfunction of the medial prefrontal cortex (mPFC) leads to social deficits in an NL3 R451C knockin (KI) mouse model of autism. However, the underlying molecular mechanism remains unclear. Here, we find that N-methyl-D-aspartate receptor (NMDAR) function and parvalbumin-positive (PV+) interneuron number and expression are reduced in the mPFC of the KI mice. Selective knockdown of NMDAR subunit GluN1 in the mPFC PV+ interneuron decreases its intrinsic excitability. Restoring NMDAR function by its partial agonist D-cycloserine rescues the PV+ interneuron dysfunction and social deficits in the KI mice. Interestingly, early D-cycloserine administration at adolescence prevents adult KI mice from social deficits. Together, our results suggest that NMDAR hypofunction and the resultant PV+ interneuron dysfunction in the mPFC may constitute a central node in the pathogenesis of social deficits in the KI mice.

Lien vers le texte intégral (Open Access ou abonnement)

8. Cesana M, Vaccaro L, Larsen MJ, Kibæk M, Micale L, Riccardo S, Annunziata P, Colantuono C, Di Filippo L, De Brasi D, Castori M, Fagerberg C, Acquaviva F, Cacchiarelli D. Integrated exome and transcriptome analysis prioritizes MAP4K4 de novo frameshift variants in autism spectrum disorder as a novel disease-gene association. Human genetics. 2022.

The application of next-generation sequencing (NGS) to clinical practice is still hampered by the ability to interpret the clinical relevance of novel variants and the difficulty of evaluating their effect in specific tissues. Here, we applied integrated genomic approaches for interrogating blood samples of two unrelated individuals with neurodevelopmental disorders and identified a novel neuro-pathogenic role for the Mitogen-Activated Protein Kinase 4 gene (MAP4K4). In particular, we identified two novel frameshift variants in coding exons expressed in the blood and neuronal isoforms. Both variants were predicted to generate non-sense-mediated decay. By transcriptome analysis, we simultaneously demonstrated the deleterious effect of the identified variants on the splicing activity and stability of MAP4K4 mRNA. Therefore, we propose MAP4K4 as a novel causative gene for non-syndromic and syndromic neurodevelopmental disorders. Altogether, we prove the efficacy of an integrated approach of exome and transcriptome sequencing in the resolution of undiagnosed cases by leveraging the analysis of variants in genes expressed in peripheral blood.

Lien vers le texte intégral (Open Access ou abonnement)

9. Cogram P, Fernández-Beltrán LC, Casarejos MJ, Sánchez-Yepes S, Rodríguez-Martín E, García-Rubia A, Sánchez-Barrena MJ, Gil C, Martínez A, Mansilla A. The inhibition of NCS-1 binding to Ric8a rescues fragile X syndrome mice model phenotypes. Frontiers in neuroscience. 2022; 16: 1007531.

Fragile X syndrome (FXS) is caused by the loss of function of Fragile X mental retardation protein (FMRP). FXS is one of the leading monogenic causes of intellectual disability (ID) and autism. Although it is caused by the failure of a single gene, FMRP that functions as an RNA binding protein affects a large number of genes secondarily. All these genes represent hundreds of potential targets and different mechanisms that account for multiple pathological features, thereby hampering the search for effective treatments. In this scenario, it seems desirable to reorient therapies toward more general approaches. Neuronal calcium sensor 1 (NCS-1), through its interaction with the guanine-exchange factor Ric8a, regulates the number of synapses and the probability of the release of a neurotransmitter, the two neuronal features that are altered in FXS and other neurodevelopmental disorders. Inhibitors of the NCS-1/Ric8a complex have been shown to be effective in restoring abnormally high synapse numbers as well as improving associative learning in FMRP mutant flies. Here, we demonstrate that phenothiazine FD44, an NCS-1/Ric8a inhibitor, has strong inhibition ability in situ and sufficient bioavailability in the mouse brain. More importantly, administration of FD44 to two different FXS mouse models restores well-known FXS phenotypes, such as hyperactivity, associative learning, aggressive behavior, stereotype, or impaired social approach. It has been suggested that dopamine (DA) may play a relevant role in the behavior and in neurodevelopmental disorders in general. We have measured DA and its metabolites in different brain regions, finding a higher metabolic rate in the limbic area, which is also restored with FD44 treatment. Therefore, in addition to confirming that the NCS-1/Ric8a complex is an excellent therapeutic target, we demonstrate the rescue effect of its inhibitor on the behavior of cognitive and autistic FXS mice and show DA metabolism as a FXS biochemical disease marker.

Lien vers le texte intégral (Open Access ou abonnement)

10. Corti L, Zanetti M, Tricella G, Bonati M. Social media analysis of Twitter tweets related to ASD in 2019-2020, with particular attention to COVID-19: topic modelling and sentiment analysis. Journal of big data. 2022; 9(1): 113.

BACKGROUND: Social media contains an overabundance of health information relating to people living with different type of diseases. Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong impacts and reported trends have revealed a considerable increase in prevalence and incidence. Research had shown that the ASD community provides significant support to its members through Twitter, providing information about their values and perceptions through their use of words and emotional stance. Our purpose was to analyze all the messages posted on Twitter platform regarding ASD and analyze the topics covered within the tweets, to understand the attitude of the various people interested in the topic. In particular, we focused on the discussion of ASD and COVID-19. METHODS: The data collection process was based on the search for tweets through hashtags and keywords. After bots screening, the NMF (Non-Negative Matrix Factorization) method was used for topic modeling because it produces more coherent topics compared to other solutions. Sentiment scores were calculated using AFiNN for each tweet to represent its negative to positive emotion. RESULTS: From the 2.458.929 tweets produced in 2020, 691.582 users were extracted (188 bots which generated 59.104 tweets), while from the 2.393.236 total tweets from 2019, the number of identified users was 684.032 (230 bots which generated 50.057 tweets). The total number of COVID-ASD tweets is only a small part of the total dataset. Often, the negative sentiment identified in the sentiment analysis referred to anger towards COVID-19 and its management, while the positive sentiment reflected the necessity to provide constant support to people with ASD. CONCLUSIONS: Social media contributes to a great discussion on topics related to autism, especially with regards to focus on family, community, and therapies. The COVID-19 pandemic increased the use of social media, especially during the lockdown period. It is important to help develop and distribute appropriate, evidence-based ASD-related information.

Lien vers le texte intégral (Open Access ou abonnement)

11. de Almeida PC, Zandonadi RP, Nakano EY, Vasconcelos IAL, Botelho RBA. Food Neophobia in Children with Autistic Spectrum Disorder (ASD): A Nationwide Study in Brazil. Children (Basel, Switzerland). 2022; 9(12).

Food neophobia (FN) is common among children with autistic spectrum disorder (ASD), potentially impairing their health and diet quality. This study aimed to investigate and classify the prevalence of FN among 4-to-11-year-old Brazilian children with ASD. This descriptive cross-sectional study was performed by applying online a validated instrument to identify FN in Brazilian children with ASD through their caregivers’ responses for a national prevalence of FN in this group. The final sample included 593 children with ASD, 80.1% of boys, with a mean age of 6.72 ± 2.31 years, and 83% having only ASD. Almost 75% (n = 436) of the children with ASD had high food neophobia scores. The fruit neophobia domain had the lowest prevalence of high neophobia (63.7%). No significant difference in FN (total, fruit, and vegetable domains) was found, considering gender and age. There was no statistical difference in FN (all domains) by the number of residents in the same household, income, or the caregivers’ educational level. FN did not decrease in older children with ASD. FN is a more complex problem, requiring a multidisciplinary trained team to face the problem.

Lien vers le texte intégral (Open Access ou abonnement)

12. Gaines R, Korneluk Y, Quigley D, Chiasson V, Delehanty A, Jacobson S. Quickstart for toddlers with autism spectrum disorder: A preliminary report of an adapted community-based early intervention program. Autism & developmental language impairments. 2022; 7: 23969415221138699.

BACKGROUND AND AIMS: Early intervention (EI) for young children with autism spectrum disorder (ASD) must be resource-efficient while remaining effective; thus, clinicians are challenged to create and implement useful methods. Clinical evidence from community-based interventions that include reliable diagnoses, individual EI programs, along with comprehensive descriptions of participants, procedures, and participant outcomes can inform practice, translational research, and local policy. Parent-mediated EI for toddlers with ASD can promote positive developmental outcomes and lifelong well-being, but evidence of successful community uptake of research-based EIs is somewhat limited. The community-based, parent-mediated, evidence-informed QuickStart EI program aims to encourage toddlers’ early social communication, social interactions, and relationship-building, in a community clinic setting.We aim to (1) describe our adaptations to the evidence-based Parent-Delivered Early Start Denver Model and (2) present promising findings for toddlers with or at risk for ASD and their families who received QuickStart. We also intend to motivate a similar study of EI in real-world situations to advance evidence-based practice and create relevant dialogue and questions for research. METHODS: Complete data were identified and analyzed for up to 89 toddlers diagnosed with, or at risk of, ASD. Pre- and post-intervention parent- or self-report data were analyzed using descriptive statistics and paired-sample t-tests, as appropriate. Pre-intervention measures included demographic information (n = 89) and the Early Screening of Autism and Communication (ESAC; n = 89). Measures taken pre- and post-intervention included the Adaptive Behavior Assessment System-II (n = 60), MacArthur-Bates Communication Development Inventories (n = 58), and the parental sense of competence scale (n = 62). The Measure of Processes of Care (n = 60) was taken post-intervention. On enrollment, parents signed standard clinical agreements that included statements allowing their anonymous data to be analyzed for research. RESULTS: Using standardized parent/self-report measures, toddler gains were noted for social interaction, language, communication skills, and ASD symptoms, but not for parents’ feelings of competence. Parents identified QuickStart procedures as family centered (Measure of Processes of Care). CONCLUSIONS: The QuickStart EI program, provided to toddlers and their families over 20 weeks in a community clinic, resulted in promising positive behavior and communication changes, as indicated on the parent-response measures, for a moderately large sample of toddlers. IMPLICATIONS: This study adds to the literature by describing a new EI program with clear procedures by which clinicians can create, provide, and evaluate a readily accessible, community-based EI for toddlers with or at risk of ASD. Methodological limitations inherent to our study design that precluded a control group and necessitated a reliance on available parent-report data are carefully critiqued and discussed.

Lien vers le texte intégral (Open Access ou abonnement)

13. Garrido D, Carballo G. Linguistic and motor profiles in preschool and school-age children with an older sibling with autism spectrum disorder. Journal of child language. 2022: 1-19.

This study examines receptive-expressive language, gross-fine motor skills, and IQ abilities in 78 children, 43 children with an older sibling with autism spectrum disorder (Sibs-ASD) and 35 children with an older sibling with typical development, ranging from 4 to 11 years of age. Depending on age, both groups were divided in preschool and school groups. The results show that more than 76% of Sibs-ASD performed at least one language and/or motor skill under 25th percentile. Significant differences were described at preschool stage in three aspects: grammatical comprehension, ball skills, and global motor skills. At school age, significant differences were found in two aspects: expressive language, and ball skills. Some differences seem to decrease over time; meanwhile others seem to increase; and others remain stable. Thus, it seems that vulnerability continues in unaffected Sibs-ASD and suggest that this population may benefit from continued screening and monitoring into the preschool and school-age stages.

Lien vers le texte intégral (Open Access ou abonnement)

14. Hu C, Li H, Li J, Luo X, Hao Y. Microglia: Synaptic modulator in autism spectrum disorder. Frontiers in psychiatry. 2022; 13: 958661.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable impairment of social communication and repetitive behaviors, highly restricted interests, and/or sensory behaviors beginning early in life. Many individuals with ASD have dysfunction of microglia, which may be closely related to neuroinflammation, making microglia play an important role in the pathogenesis of ASD. Mounting evidence indicates that microglia, the resident immune cells of the brain, are required for proper brain function, especially in the maintenance of neuronal circuitry and control of behavior. Dysfunction of microglia will ultimately affect the neural function in a variety of ways, including the formation of synapses and alteration of excitatory-inhibitory balance. In this review, we provide an overview of how microglia actively interact with neurons in physiological conditions and modulate the fate and functions of synapses. We put a spotlight on the multi-dimensional neurodevelopmental roles of microglia, especially in the essential influence of synapses, and discuss how microglia are currently thought to influence ASD progression.

Lien vers le texte intégral (Open Access ou abonnement)

15. Hughes HK, Moreno RJ, Ashwood P. Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD). Brain, behavior, and immunity. 2022; 108: 245-54.

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by communication and social behavior deficits. The presence of restricted and repetitive behaviors often accompanies these deficits, and these characteristics can range from mild to severe. The past several decades have seen a significant rise in the prevalence of ASD. The etiology of ASD remains unknown; however, genetic and environmental risk factors play a role. Multiple hypotheses converge to suggest that neuroinflammation, or at least the interaction between immune and neural systems, may be involved in the etiology of some ASD cases or groups. Repeated evidence of innate immune dysfunction has been seen in ASD, often associated with worsening behaviors. This evidence includes data from circulating myeloid cells and brain resident macrophages/microglia in both human and animal models. This comprehensive review presents recent findings of innate immune dysfunction in ASD, including aberrant innate cellular function, evidence of neuroinflammation, and microglia activation.

Lien vers le texte intégral (Open Access ou abonnement)

16. Jacokes Z, Jack A, Sullivan CAW, Aylward E, Bookheimer SY, Dapretto M, Bernier RA, Geschwind DH, Sukhodolsky DG, McPartland JC, Webb SJ, Torgerson CM, Eilbott J, Kenworthy L, Pelphrey KA, Van Horn JD. Linear discriminant analysis of phenotypic data for classifying autism spectrum disorder by diagnosis and sex. Frontiers in neuroscience. 2022; 16: 1040085.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by social and communication differences. Recent research suggests ASD affects 1-in-44 children in the United States. ASD is diagnosed more commonly in males, though it is unclear whether this diagnostic disparity is a result of a biological predisposition or limitations in diagnostic tools, or both. One hypothesis centers on the ‘female protective effect,’ which is the theory that females are biologically more resistant to the autism phenotype than males. In this examination, phenotypic data were acquired and combined from four leading research institutions and subjected to multivariate linear discriminant analysis. A linear discriminant model was trained on the training set and then deployed on the test set to predict group membership. Multivariate analyses of variance were performed to confirm the significance of the overall analysis, and individual analyses of variance were performed to confirm the significance of each of the resulting linear discriminant axes. Two discriminant dimensions were identified between the groups: a dimension separating groups by the diagnosis of ASD (LD1: 87% of variance explained); and a dimension reflective of a diagnosis-by-sex interaction (LD2: 11% of variance explained). The strongest discriminant coefficients for the first discriminant axis divided the sample in domains with known differences between ASD and comparison groups, such as social difficulties and restricted repetitive behavior. The discriminant coefficients for the second discriminant axis reveal a more nuanced disparity between boys with ASD and girls with ASD, including executive functioning and high-order behavioral domains as the dominant discriminators. These results indicate that phenotypic differences between males and females with and without ASD are identifiable using parent report measures, which could be utilized to provide additional specificity to the diagnosis of ASD in female patients, potentially leading to more targeted clinical strategies and therapeutic interventions. The study helps to isolate a phenotypic basis for future empirical work on the female protective effect using neuroimaging, EEG, and genomic methodologies.

Lien vers le texte intégral (Open Access ou abonnement)

17. Jelili S, Halayem S, Rajhi O, Abbes Z, Mansour HB, Ouanes S, Taamallah A, Ennaifer S, Ben Yahia H, Ghazzei M, Nabli A, Hajri M, Fakhfakh R, Mrabet A, Bouden A. Assessment of theory of mind in Tunisian verbal children with autism spectrum disorder. Frontiers in psychiatry. 2022; 13: 922873.

The present study examined performance in Theory of Mind (ToM) in a group of 31 Arabic-speaking verbal children (7-12 years-old) with autism spectrum disorder (ASD), in comparison with neurotypical controls (NT) matched for age and for cognitive abilities. An innovative task in a digital format named « The Tunisian Social Situations Instrument » (TSSI) was used and allowed us to study four different subdomains of ToM: attribution of intention and epistemic ToM (cognitive ToM), affective ToM, and detection of faux pas (advanced ToM). Our study showed impairments in ToM in children with ASD, similar to those reported in the literature. Our findings additionally suggested that affective and advanced ToM, specifically the detection of faux pas, might be more challenging for ASD children than other components of ToM. Future studies with larger number of children may lead us to specify which subdomains are the most impaired in order to develop specific tools targeting these specific impairments.

Lien vers le texte intégral (Open Access ou abonnement)

18. Keating CT, Hickman L, Leung J, Monk R, Montgomery A, Heath H, Sowden S. Autism-related language preferences of English-speaking individuals across the globe: A mixed methods investigation. Autism research : official journal of the International Society for Autism Research. 2022.

Over the past two decades, there have been increasing discussions around which terms should be used to talk about autism. Whilst these discussions have largely revolved around the suitability of identity-first language and person-first language, more recently this debate has broadened to encompass other autism-related terminology (e.g., ‘high-functioning’). To date, academic studies have not investigated the language preferences of autistic individuals outside of the United Kingdom or Australia, nor have they compared levels of endorsement across countries. Hence, the current study adopted a mixed-methods approach, employing both quantitative and qualitative techniques, to explore the linguistic preferences of 654 English-speaking autistic adults across the globe. Despite variation in levels of endorsement between countries, we found that the most popular terms were similar-the terms ‘Autism’, ‘Autistic person’, ‘Is autistic’, ‘Neurological/Brain Difference’, ‘Differences’, ‘Challenges’, ‘Difficulties’, ‘Neurotypical people’, and ‘Neurotypicals’ were consistently favored across countries. Despite relative consensus across groups, both our quantitative and qualitative data demonstrate that there is no universally accepted way to talk about autism. Our thematic analysis revealed the reasons underlying participants’ preferences, generating six core themes, and illuminated an important guiding principle-to respect personal preferences. These findings have significant implications for informing practice, research and language policy worldwide.

Lien vers le texte intégral (Open Access ou abonnement)

19. Kim Y, Jeon SJ, Gonzales EL, Shin D, Remonde CG, Ahn T, Shin CY. Pirenperone relieves the symptoms of fragile X syndrome in Fmr1 knockout mice. Scientific reports. 2022; 12(1): 20966.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by the loss of Fragile X-linked mental retardation protein (FMRP), an RNA binding protein that can bind and recognize different RNA structures and regulate the target mRNAs’ translation involved in neuronal synaptic plasticity. Perturbations of this gene expression network have been related to abnormal behavioral symptoms such as hyperactivity, and impulsivity. Considering the roles of FMRP in the modulation of mRNA translation, we investigated the differentially expressed genes which might be targeted to revert to normal and ameliorate behavioral symptoms. Gene expression data was analyzed and used the connectivity map (CMap) to understand the changes in gene expression in FXS and predict the effective drug candidates. We analyzed the GSE7329 dataset that had 15 control and 8 FXS patients’ lymphoblastoid samples. Among 924 genes, 42 genes were selected as signatures for CMap analysis, and 24 associated drugs were found. Pirenperone was selected as a potential drug candidate for FXS for its possible antipsychotic effect. Treatment of pirenperone increased the expression level of Fmr1 gene. Moreover, pirenperone rescued the behavioral deficits in Fmr1 KO mice including hyperactivity, spatial memory, and impulsivity. These results suggest that pirenperone is a new drug candidate for FXS, which should be verified in future studies.

Lien vers le texte intégral (Open Access ou abonnement)

20. Kirjava SA, Witham K. Practical and ethical considerations for neurodiversity inclusion in audiology education and practice. Trends in neuroscience and education. 2022; 29: 100185.

BACKGROUND: . An increasing number of people who are neurodiverse (people who have conditions such as autism, ADHD, and dyslexia) are pursuing higher education, including education and employment in the field of audiology METHODS: . This conceptual article was written by neurodivergent professionals to promote a cultural shift of inclusion for students, clinicians, researchers, and professors who identify as neurodivergent. FINDINGS: . People with these conditions thrive with supportive accommodations in higher education and workplaces but little has been reported in the literature on neurodiversity accommodations in audiology education and practice CONCLUSIONS: . This article reviews the current literature on neurodiversity as it relates to audiology and discusses the practical and ethical considerations for neurodiversity inclusivity in the discipline of audiology.

Lien vers le texte intégral (Open Access ou abonnement)

21. Li Y, Fan T, Li X, Liu L, Mao F, Li Y, Miao Z, Zeng C, Song W, Pan J, Zhou S, Sunday ME, Wang H, Wang Y, Sun ZS. Npas3 deficiency impairs cortical astrogenesis and induces autistic-like behaviors. Cell reports. 2022; 41(10): 111767.

Lien vers le texte intégral (Open Access ou abonnement)

22. Li Y, Wei Z, Shao M, Hong M, Yang D, Luo L, Meng J. Empathy for pain in individuals with autistic traits during observation of static and dynamic stimuli. Frontiers in psychiatry. 2022; 13: 1022087.

Previous studies have reported that individuals with autistic traits, like those with Autism Spectrum Disorder (ASD), may have impaired empathic responses when observing static stimuli of others’ pain. However, it remains unclear whether individuals with autistic traits exhibit impaired empathy for pain in response to dynamic stimuli. The present study addressed this question by recruiting 529 individuals whose autistic traits were assessed using the autism-spectrum quotient (AQ) questionnaire. Thirty participants who scored within the top 10% and bottom 10% on the AQ were selected into High-AQ and Low-AQ groups, respectively. This study employed painful whole-body action pictures and videos as static and dynamic stimuli. Both groups were instructed to judge whether the models in the stimuli were experiencing pain, and their reaction times, accuracy and event-related potential (ERP) data were recorded. Results showed that the P2 amplitudes were larger in the High-AQ group than in the Low-AQ group when viewing painful static stimuli, while no difference between the two groups was found when viewing painful dynamic stimuli. These results suggest that autistic traits influenced the emotional processing of others’ pain in response to static stimuli.

Lien vers le texte intégral (Open Access ou abonnement)

23. Liang Q, Liu Y, Liu Y, Duan R, Meng W, Zhan J, Xia J, Mao A, Liang D, Wu L. Comprehensive Analysis of Fragile X Syndrome: Full Characterization of the FMR1 Locus by Long-Read Sequencing. Clinical chemistry. 2022; 68(12): 1529-40.

BACKGROUND: Fragile X syndrome (FXS) is the most frequent cause of inherited X-linked intellectual disability. Conventional FXS genetic testing methods mainly focus on FMR1 CGG expansions and fail to identify AGG interruptions, rare intragenic variants, and large gene deletions. METHODS: A long-range PCR and long-read sequencing-based assay termed comprehensive analysis of FXS (CAFXS) was developed and evaluated in Coriell and clinical samples by comparing to Southern blot analysis and triplet repeat-primed PCR (TP-PCR). RESULTS: CAFXS accurately detected the number of CGG repeats in the range of 93 to at least 940 with mass fraction of 0.5% to 1% in the background of normal alleles, which was 2-4-fold analytically more sensitive than TP-PCR. All categories of mutations detected by control methods, including full mutations in 30 samples, were identified by CAFXS for all 62 clinical samples. CAFXS accurately determined AGG interruptions in all 133 alleles identified, even in mosaic alleles. CAFXS successfully identified 2 rare intragenic variants including the c.879A > C variant in exon 9 and a 697-bp microdeletion flanking upstream of CGG repeats, which disrupted primer annealing in TP-PCR assay. In addition, CAFXS directly determined the breakpoints of a 237.1-kb deletion and a 774.0-kb deletion encompassing the entire FMR1 gene in 2 samples. CONCLUSIONS: Long-read sequencing-based CAFXS represents a comprehensive assay for identifying FMR1 CGG expansions, AGG interruptions, rare intragenic variants, and large gene deletions, which greatly improves the genetic screening and diagnosis for FXS.

Lien vers le texte intégral (Open Access ou abonnement)

24. Locke J, Hernandez AM, Joshi M, Hugh ML, Bravo A, Osuna A, Pullmann MD. Supporting the inclusion and retention of autistic students: Exploring teachers’ and paraeducators’ use of evidence-based practices in public elementary schools. Frontiers in psychiatry. 2022; 13: 961219.

INTRODUCTION: Educators in public schools are required to serve students in their least restrictive environment. While many evidence-based practices (EBPs), defined as practices and strategies shown by research to have meaningful effectson outcomes for autistic students are documented in the literature, less is known about EBP use among educators in public schools. METHODS: Eighty-six general and special education teachers and para educators completed a survey about familiarity, training, and EBP use for included autistic children. RESULTS: Across roles, educators reported familiarity (98.8%), use (97.7%), and training (83.7%) in reinforcement. They reported the least familiarity with behavioral momentum (29.1%), training in both video modeling and peer-mediated instruction and intervention (18.6%), and use of video modeling (14.0%). Follow-up interviews (n = 80) highlighted mixed understanding of EBP definitions and use. DISCUSSION: Implications for inclusive education are discussed including autism-specific EBP training within pre-service teacher preparation programs.

Lien vers le texte intégral (Open Access ou abonnement)

25. Louros SR, Seo SS, Maio B, Martinez-Gonzalez C, Gonzalez-Lozano MA, Muscas M, Verity NC, Wills JC, Li KW, Nolan MF, Osterweil EK. Excessive proteostasis contributes to pathology in fragile X syndrome. Neuron. 2022.

In fragile X syndrome (FX), the leading monogenic cause of autism, excessive neuronal protein synthesis is a core pathophysiology; however, an overall increase in protein expression is not observed. Here, we tested whether excessive protein synthesis drives a compensatory rise in protein degradation that is protective for FX mouse model (Fmr1(-/y)) neurons. Surprisingly, although we find a significant increase in protein degradation through ubiquitin proteasome system (UPS), this contributes to pathological changes. Normalizing proteasome activity with bortezomib corrects excessive hippocampal protein synthesis and hyperactivation of neurons in the inferior colliculus (IC) in response to auditory stimulation. Moreover, systemic administration of bortezomib significantly reduces the incidence and severity of audiogenic seizures (AGS) in the Fmr1(-/y) mouse, as does genetic reduction of proteasome, specifically in the IC. Together, these results identify excessive activation of the UPS pathway in Fmr1(-/y) neurons as a contributor to multiple phenotypes that can be targeted for therapeutic intervention.

Lien vers le texte intégral (Open Access ou abonnement)

26. Munuera-Cabeza M, Álvarez-Córdoba M, Suárez-Rivero JM, Povea-Cabello S, Villalón-García I, Talaverón-Rey M, Suárez-Carrillo A, Reche-López D, Cilleros-Holgado P, Piñero-Pérez R, Sánchez-Alcázar JA. Pantothenate and L-Carnitine Supplementation Improves Pathological Alterations in Cellular Models of KAT6A Syndrome. Genes. 2022; 13(12).

Mutations in several genes involved in the epigenetic regulation of gene expression have been considered risk alterations to different intellectual disability (ID) syndromes associated with features of autism spectrum disorder (ASD). Among them are the pathogenic variants of the lysine-acetyltransferase 6A (KAT6A) gene, which causes KAT6A syndrome. The KAT6A enzyme participates in a wide range of critical cellular functions, such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiological alterations in fibroblasts derived from three patients harboring KAT6A mutations. We addressed survival in a stress medium, histone acetylation, protein expression patterns, and transcriptome analysis, as well as cell bioenergetics. In addition, we evaluated the therapeutic effectiveness of epigenetic modulators and mitochondrial boosting agents, such as pantothenate and L-carnitine, in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and partially corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, the cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly improve the mutant phenotype in cellular models of KAT6A syndrome.

Lien vers le texte intégral (Open Access ou abonnement)

27. Saraf TS, McGlynn RP, Bhatavdekar OM, Booth RG, Canal CE. FPT, a 2-Aminotetralin, Is a Potent Serotonin 5-HT(1A), 5-HT(1B), and 5-HT(1D) Receptor Agonist That Modulates Cortical Electroencephalogram Activity in Adult Fmr1 Knockout Mice. ACS chemical neuroscience. 2022; 13(24): 3629-40.

There are no approved medicines for fragile X syndrome (FXS), a monogenic, neurodevelopmental disorder. Electroencephalogram (EEG) studies show alterations in resting-state cortical EEG spectra, such as increased gamma-band power, in patients with FXS that are also observed in Fmr1 knockout models of FXS, offering putative biomarkers for drug discovery. Genes encoding serotonin receptors (5-HTRs), including 5-HT(1A), 5-HT(1B), and 5-HT(1D)Rs, are differentially expressed in FXS, providing a rationale for investigating them as pharmacotherapeutic targets. Previously we reported pharmacological activity and preclinical neurotherapeutic effects in Fmr1 knockout mice of an orally active 2-aminotetralin, (S)-5-(2′-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FPT). FPT is a potent (low nM), high-efficacy partial agonist at 5-HT(1A)Rs and a potent, low-efficacy partial agonist at 5-HT(7)Rs. Here we report new observations that FPT also has potent and efficacious agonist activity at human 5-HT(1B) and 5-HT(1D)Rs. FPT’s K(i) values at 5-HT(1B) and 5-HT(1D)Rs were <5 nM, but it had nil activity (>10 μM K(i)) at 5-HT(1F)Rs. We tested the effects of FPT (5.6 mg/kg, subcutaneous) on EEG recorded above the somatosensory and auditory cortices in freely moving, adult Fmr1 knockout and control mice. Consistent with previous reports, we observed significantly increased relative gamma power in untreated or vehicle-treated male and female Fmr1 knockout mice from recordings above the left somatosensory cortex (LSSC). In addition, we observed sex effects on EEG power. FPT did not eliminate the genotype difference in relative gamma power from the LSSC. FPT, however, robustly decreased relative alpha power in the LSSC and auditory cortex, with more pronounced effects in Fmr1 KO mice. Similarly, FPT decreased relative alpha power in the right SSC but only in Fmr1 knockout mice. FPT also increased relative delta power, with more pronounced effects in Fmr1 KO mice and caused small but significant increases in relative beta power. Distinct impacts of FPT on cortical EEG were like effects caused by certain FDA-approved psychotropic medications (including baclofen, allopregnanolone, and clozapine). These results advance the understanding of FPT’s pharmacological and neurophysiological effects.

Lien vers le texte intégral (Open Access ou abonnement)

28. Smith AA, Forero M, Finkelman MD, Dolan K. A dental desensitization program for children with autism spectrum disorder. Journal of dental education. 2022.

Lien vers le texte intégral (Open Access ou abonnement)

29. Staton A, Dawson D, Moghaddam N, McGrath B. Specificity and sensitivity of the social communication questionnaire lifetime screening tool for autism spectrum disorder in a UK CAMHS service. Clinical child psychology and psychiatry. 2022: 13591045221137196.

INTRODUCTION: The Social Communication Questionnaire is used to identify children and young people (CYP) who may require formal ASD assessment. However, there is a paucity of research on its utility in Children and Adolescent Mental Health Services. This evaluation aimed to determine the sensitivity and specificity of the Social Communication Questionnaire (SCQ) in a UK, Midlands CAMHS service. METHOD: Forty young people (mean age 13.75 years) were screened using the caregiver reported SCQ before completing ‘gold standard’ assessment. RESULTS: The SCQ had a sensitivity of 80% and a specificity of 25.7%. ROC curve analysis indicated low diagnostic accuracy. Differences in predictive accuracy of SCQ and diagnostic standard were statistically significant (p < 0.0001). CONCLUSION: This evaluation builds on previous research suggesting that the SCQ may not be an efficient screening tool in CAMHS settings.

Lien vers le texte intégral (Open Access ou abonnement)

30. Sun JJ, Chen B, Yu T. Construction of an immune-related ceRNA network to screen for potential diagnostic markers for autism spectrum disorder. Frontiers in genetics. 2022; 13: 1025813.

Purpose: The diagnosis of autism spectrum disorder (ASD) is reliant on evaluation of patients’ behavior. We screened the potential diagnostic and therapeutic targets of ASD through bioinformatics analysis. Methods: Four ASD-related datasets were downloaded from the Gene Expression Omnibus database. The « limma » package was employed to analyze differentially expressed messenger (m)RNAs, long non-coding (lnc)RNAs, and micro (mi)RNAs between ASD patients and healthy volunteers (HVs). We constructed a competing endogenous-RNA (ceRNA) network. Enrichment analyses of key genes were undertaken using the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database. The ImmucellAI database was used to analyze differences in immune-cell infiltration (ICI) in ASD and HV samples. Synthetic analyses of the ceRNA network and ICI was done to obtain a diagnostic model using LASSO regression analysis. Analyses of receiver operating characteristic (ROC) curves were done for model verification. Results: The ceRNA network comprised 49 lncRNAs, 30 miRNAs, and 236 mRNAs. mRNAs were associated with 41 cellular components, 208 biological processes, 39 molecular functions, and 35 regulatory signaling pathways. Significant differences in the abundance of 10 immune-cell species between ASD patients and HVs were noted. Using the ceRNA network and ICI results, we constructed a diagnostic model comprising five immune cell-associated genes: adenosine triphosphate-binding cassette transporter A1 (ABCA1), DiGeorge syndrome critical region 2 (DGCR2), glucose-fructose oxidoreductase structural domain gene 1 (GFOD1), glutaredoxin (GLRX), and SEC16 homolog A (SEC16A). The diagnostic performance of our model was revealed by an area under the ROC curve of 0.923. Model verification was done using the validation dataset and serum samples of patients. Conclusion: ABCA1, DGCR2, GFOD1, GLRX, and SEC16A could be diagnostic biomarkers and therapeutic targets for ASD.

Lien vers le texte intégral (Open Access ou abonnement)

31. Talesh Jafadideh A, Mohammadzadeh Asl B. Structural filtering of functional data offered discriminative features for autism spectrum disorder. PloS one. 2022; 17(12): e0277989.

This study attempted to answer the question, « Can filtering the functional data through the frequency bands of the structural graph provide data with valuable features which are not valuable in unfiltered data »?. The valuable features discriminate between autism spectrum disorder (ASD) and typically control (TC) groups. The resting-state fMRI data was passed through the structural graph’s low, middle, and high-frequency band (LFB, MFB, and HFB) filters to answer the posed question. The structural graph was computed using the diffusion tensor imaging data. Then, the global metrics of functional graphs and metrics of functional triadic interactions were computed for filtered and unfiltered rfMRI data. Compared to TCs, ASDs had significantly higher clustering coefficients in the MFB, higher efficiencies and strengths in the MFB and HFB, and lower small-world propensity in the HFB. These results show over-connectivity, more global integration, and decreased local specialization in ASDs compared to TCs. Triadic analysis showed that the numbers of unbalanced triads were significantly lower for ASDs in the MFB. This finding may indicate the reason for restricted and repetitive behavior in ASDs. Also, in the MFB and HFB, the numbers of balanced triads and the energies of triadic interactions were significantly higher and lower for ASDs, respectively. These findings may reflect the disruption of the optimum balance between functional integration and specialization. There was no significant difference between ASDs and TCs when using the unfiltered data. All of these results demonstrated that significant differences between ASDs and TCs existed in the MFB and HFB of the structural graph when analyzing the global metrics of the functional graph and triadic interaction metrics. Also, these results demonstrated that frequency bands of the structural graph could offer significant findings which were not found in the unfiltered data. In conclusion, the results demonstrated the promising perspective of using structural graph frequency bands for attaining discriminative features and new knowledge, especially in the case of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

32. Tang S, Liu X, Nie L, Chen Z, Ran Q, He L. Diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) comorbid autistic traits (ATs) by applying quantitative magnetic resonance imaging techniques. Frontiers in psychiatry. 2022; 13: 1038471.

OBJECTIVE: To explore the feasibility of applying quantitative magnetic resonance imaging techniques for the diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) comorbid autistic traits (ATs). METHODS: A prospective study was performed by selecting 56 children aged 4-5 years with ADHD-ATs as the study group and 53 sex- and age-matched children with ADHD without ATs as the control group. All children underwent magnetic resonance scans with enhanced T2(*)- weighted magnetic resonance angiography (ESWAN), 3D-PCASL, and 3D-T1 sequences. Iron content and cerebral blood flow parameters were obtained via subsequent software processing, and the parameter values in particular brain regions in both groups were compared and analyzed to determine the characteristics of these parameters in children with ADHD-ATs. RESULTS: Iron content and cerebral blood flow in the frontal lobe, temporal lobe, hippocampus, and caudate nucleus of children with ADHD-ATs were lower than those of children with ADHD without ATs (p < 0.05). Iron content and CBF values in the frontal lobe, temporal lobe and caudate nucleus could distinguish children with ADHD-ATs from those without ATs (AUC > 0.5, p < 0.05). CONCLUSIONS: Quantitative magnetic resonance techniques could distinguish children with ADHD-ATs. TRIAL REGISTRATION: This study protocol was registered at the Chinese clinical trial registry (ChiCTR2100046616).

Lien vers le texte intégral (Open Access ou abonnement)

33. Thomson S, Drummond K, O’Hely M, Symeonides C, Chandran C, Mansell T, Saffery R, Sly P, Mueller J, Vuillermin P, Ponsonby AL. Increased maternal non-oxidative energy metabolism mediates association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and offspring autism spectrum disorder symptoms in early life: A birth cohort study. Environment international. 2022; 171: 107678.

Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study (BIS), a population-based birth cohort of 1,074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord serum at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured in 596 and 674 children by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) prospective associations between higher prenatal di-(2-ethylhexyl) phthalate (DEHP) levels and upregulation of maternal non-oxidative energy metabolism pathways, and (ii) prospective associations between upregulation of these pathways and increased offspring ASD symptoms at 2 and 4 years of age. Counterfactual mediation analyses indicated that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. These results highlight the importance of the prenatal period and suggest that further investigation of maternal energy metabolism as a molecular mediator of the adverse impact of prenatal environmental exposures such as phthalates is warranted.

Lien vers le texte intégral (Open Access ou abonnement)

34. Tirani SA, Balali A, Askari G, Saneei P. Maternal serum 25-hydroxy vitamin D levels and risk of autism spectrum and attention-deficit hyperactivity disorders in offspring: A systematic review and dose-response meta-analysis. Psychiatry research. 2022; 319: 114977.

Lien vers le texte intégral (Open Access ou abonnement)

35. Tsiplova K, Ungar WJ, Szatmari P, Cost K, Pullenayegum E, Duku E, Volden J, Smith IM, Waddell C, Zwaigenbaum L, Bennett TA, Elsabbagh M, Georgiades S, Zaidman-Zait A. Measuring the association between behavioural services and outcomes in young children with autism spectrum disorder. Research in developmental disabilities. 2023; 132: 104392.

BACKGROUND: Children with autism spectrum disorder (ASD) receive a wide range of services. AIMS: To examine the association between behavioural services received by children with ASD between ages 2 and 5 years and outcomes during primary school years. METHODS: A total of 414 preschool-aged children diagnosed with ASD were enrolled at five Canadian sites and were assessed within four months of diagnosis (T1), six months later (T2), 12 months later (T3), at school entry (T4), and then annually (T5-T8) to 11 years of age. The association between the receipt of behavioural services during T1 to T3 and T8 outcomes related to adaptive behaviour and behavioural problems was modelled using linear regressions adjusted for immigrant status, family income, child’s age at diagnosis, site, sex assigned at birth, and baseline (T1) outcome. RESULTS: Children who received behavioural services during at least one time period from T1 to T3 did not have significantly different outcomes at T8 than children who did not receive any behavioural services. IMPLICATIONS: Pre-school use of behavioural services was not found to affect outcomes during later childhood. Numerous challenges accompany studies of the association between pre-school service use and later outcomes in a heterogeneous ASD sample. Recommendations for study design are provided.

Lien vers le texte intégral (Open Access ou abonnement)

36. Waizbard-Bartov E, Miller M. Does the severity of autism symptoms change over time? A review of the evidence, impacts, and gaps in current knowledge. Clinical psychology review. 2022; 99: 102230.

Studies evaluating change in autism symptom severity across the lifespan have yielded inconsistent results, making it difficult to assess the prevalence of meaningful change in autism symptom severity, and what characterizes it. Better understanding the ways in which autism symptoms change over time is crucial, with important implications for intervention. Synthesizing information across past studies, autism symptom severity change (especially decreases) appears common, though stability of symptoms is also frequent. Symptom severity change is characterized by variability in patterns of change between different individuals (between-person), variability in change within a person’s trajectory across time (within-person), and variability in change patterns across symptom domains (i.e., social-communication, restricted/repetitive behaviors). Variability in severity change is likely impacted by differences in person-level characteristics (e.g., sex, IQ, sociodemographic factors) as well as developmental processes across time. Numerous methodological issues may impact our ability to understand how common change in symptom severity is, including varying measurement tools, analytic approaches, and change patterns between symptom domains across time. Potential implications of better understanding and characterizing symptom severity change include incorporation of severity change patterns and predictors of change into research on biomarkers, and consideration of such predictors as moderators or mediators of change in clinical practice.

Lien vers le texte intégral (Open Access ou abonnement)

37. Wu X, Lin F, Zhang T, Sun H, Li J. Acquisition time for functional near-infrared spectroscopy resting-state functional connectivity in assessing autism. Neurophotonics. 2022; 9(4): 045007.

SIGNIFICANCE: Resting state functional connectivity (RSFC) can be used to assess autism spectrum disorder (ASD). Measuring RSFC usually takes 5 to 10 min, during which children with ASD may have difficulty keeping their heads motionless. Therefore, a short acquisition time for RSFC would make clinical implementation more feasible. AIM: To find a suitable acquisition time necessary for measuring RSFC with functional near-infrared spectroscopy (fNIRS) for the differentiation between children with ASD and typically developing (TD) children. APPROACH: We used fNIRS to record the spontaneous hemodynamic fluctuations from the bilateral temporal lobes of 25 children with ASD and 22 TD children. The recorded signals were truncated into several segments with different time windows, and then the homotopic RSFC was computed for each of these segments and compared between the two groups. RESULTS: We observed even in a very short time duration of 0.5 min, the RSFC had already existed a significant difference between the two groups, and 2.0 min might be the minimal time required for measuring RSFC for accurate differentiation between the two groups. CONCLUSIONS: The fNIRS-RSFC acquired even in a short time, e.g., 2.0 min, might be a reliable feature for the differentiation between children with ASD and TD children.

Lien vers le texte intégral (Open Access ou abonnement)

38. Xiao L, Jiang S, Wang Y, Gao C, Liu C, Huo X, Li W, Guo B, Wang C, Sun Y, Wang A, Feng Y, Wang F, Sun T. Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model. Journal of translational medicine. 2022; 20(1): 570.

BACKGROUND: Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. METHODS: VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0-7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. RESULTS: Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. CONCLUSIONS: Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Lien vers le texte intégral (Open Access ou abonnement)

39. Xu Y, Yang X, Chen D, Xu Y, Lan L, Zhao S, Liu Q, Snijders AM, Xia Y. Maternal exposure to pesticides and autism or attention-deficit/hyperactivity disorders in offspring: A meta-analysis. Chemosphere. 2022: 137459.

OBJECTIVE: To analyze the association between maternal pesticide exposure and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorders (ADHD) in offspring. METHOD: Five databases including PubMed, Embase, Web of Science, Medline, as well as PsycINFO were systematically retrieved for the records related to pesticide exposure during pregnancy and ASD and ADHD in offspring before August 30, 2022. The pesticide category, maternal age and window of exposure as the main subgroups were presented. RESULTS: 949 studies were initially identified, and 19 studies were eventually included. Eleven were on ASD, seven were on ADHD, and one was on both disorders. Maternal pesticide exposure was positively related to ASD (pooled OR = 1.19 (95%CI: 1.04 to 1.36)) and ADHD (pooled OR = 1.20 (95%CI: 1.04 to 1.38)) in offspring. In the subgroup analysis, organophosphorus pesticides (OPs) (pooled OR = 1.14 (95%CI: 1.04 to 1.24)), pyrethroid (pooled OR = 1.40 (95%CI: 1.09 to 1.80)), and maternal age ≥30 years old (pooled OR = 1.24 (95%CI: 1.10 to 1.40)) increased the risk of ASD in offspring. Maternal organochlorine pesticides (OCPs) exposure was a risk factor for ADHD in offspring (pooled OR = 1.22 (95%CI: 1.03 to 1.45)). CONCLUSION: Maternal pesticide exposure increased the risk of ASD and ADHD in offspring. Moreover, OPs, pyrethroid, and maternal age ≥30 years old were found to be risk factors affecting children’s ASD. Maternal exposure to OCPs increased the risk of ADHD in offspring. Our findings contribute to our understanding of health risks related to maternal pesticide exposure and indicate that the in utero developmental period is a vulnerable window-of-susceptibility for ASD and ADHD risk in offspring. These findings should guide policies that limit maternal exposure to pesticides, especially for pregnant women living in agricultural areas.

Lien vers le texte intégral (Open Access ou abonnement)

40. Yang J, Shen Y, Tian Y, Peng J, Fu X, Li Y, Ou J. Investigating and comparing the psychometric properties of the Chinese Mandarin version of social responsiveness scale-2 and its shortened version in preschool-age children with autism spectrum disorder. Asian journal of psychiatry. 2022; 79: 103395.

We aimed to investigate and compare the psychometric properties of the Chinese Mandarin Social Responsiveness Scale-2 (SRS-2) and its shortened version. The study assessed 670 children with autism spectrum disorder (ASD) aged 30-54 months and 138 typical developmental (TD) children of the same age in mainland China. Our item reliability test revealed that only 36 items of the 65 items in the Chinese Mandarin SRS-2 (Preschool) met the reliability criteria. Moreover, the shortened version of SRS-2 (Preschool) with four subscales and 30 items maintained strong correlations (r = 0.961) with the Chinese Mandarin SRS-2 (Preschool), and demonstrated improved psychometric performance on the 4-week test-retest reliability (intraclass correlations was 0.70), internal consistency (Cronbach’s alpha 0.71-0.91), construct validity, and convergent validity with the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, and Child Behavior Checklist. Receiver operating characteristics (ROC) analyses showed excellent and comparable discriminant validity of the shortened version with an area under the curve of 0.992. Our data suggested a cutoff ≥ 22.5 for the shortened version, with good accuracy in screening autism symptoms (sensitivity=96.9 %, specificity=94.2 %). Our findings demonstrated that the shortened version of SRS-2 (Preschool) was a reliable and valid instrument for identifying preschoolers with ASD in mainland China.

Lien vers le texte intégral (Open Access ou abonnement)

41. Yeo XY, Lim YT, Chae WR, Park C, Park H, Jung S. Alterations of presynaptic proteins in autism spectrum disorder. Frontiers in molecular neuroscience. 2022; 15: 1062878.

The expanded use of hypothesis-free gene analysis methods in autism research has significantly increased the number of genetic risk factors associated with the pathogenesis of autism. A further examination of the implicated genes directly revealed the involvement in processes pertinent to neuronal differentiation, development, and function, with a predominant contribution from the regulators of synaptic function. Despite the importance of presynaptic function in synaptic transmission, the regulation of neuronal network activity, and the final behavioral output, there is a relative lack of understanding of the presynaptic contribution to the pathology of autism. Here, we will review the close association among autism-related mutations, autism spectrum disorders (ASD) phenotypes, and the altered presynaptic protein functions through a systematic examination of the presynaptic risk genes relating to the critical stages of synaptogenesis and neurotransmission.

Lien vers le texte intégral (Open Access ou abonnement)

42. Zhang J, Li Z, Wu Y, Ye AY, Chen L, Yang X, Wu Q, Wei L. RJAfinder: An automated tool for quantification of responding to joint attention behaviors in autism spectrum disorder using eye tracking data. Frontiers in neuroscience. 2022; 16: 915464.

Deficits in responding to joint attention (RJA) are early symptoms of autism spectrum disorder (ASD). Currently, no automated tools exist for identifying and quantifying RJA behaviors. A few eye tracking studies have investigated RJA in ASD children but have produced conflicting results. In addition, little is known about the trajectory of RJA development through developmental age. Here, a new video was designed including 12 clips of an actor pointing to or looking at an object. Eye tracking technology was used to monitor RJA in three groups: 143 ASD children assessed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) (4-7 years old), 113 age- and gender-matched typically developing children (TDC), and 43 typically developing adults (TDA) (19-32 years old). RJAfinder was developed in R and MATLAB to quantify RJA events from the eye tracking data. RJA events were compared among the three groups. Spearman correlation coefficients between total number of RJA events in ASD and the Social Responsiveness Scale (SRS) scores were calculated. A logistic regression model was built using the average valid sampling rate and the total number of RJA events as two predictive variables to classify ASD and TDC groups. ASD children displayed statistically significantly less RJA events than the TDC and TDA groups with medium-to-large-sized effects. ASD and TDC children both displayed more RJA events in response to pointing stimuli than to looking stimuli. Our logistic regression model predicted ASD tendency with 0.76 accuracy in the testing set. RJA ability improved more slowly between the ages of 4-7 years old in the ASD group than in the TDC group. In ASD children, RJA ability showed negative correlation with SRS total T-score as well as the scores of five subdomains. Our study provides an automated tool for quantifying RJA and insights for the study of RJA in ASD children, which may help improve ASD screening, subtyping, and behavior interventions.

Lien vers le texte intégral (Open Access ou abonnement)