1. Adams D, Malone S, Simpson K, Tucker M, Rapee RM, Rodgers J, Keen D. Protocol for a longitudinal study investigating the role of anxiety on academic outcomes in children on the autism spectrum. PloS one. 2021; 16(9): e0257223.

BACKGROUND: Children on the autism spectrum are consistently reported to underachieve compared to ability. In typically developing children, anxiety is a strong predictor of poor school performance. Despite the high prevalence of anxiety disorders among children on the spectrum, the impact of their anxiety on academic achievement is under-researched. The main aim of this project is to determine the moderating role anxiety may have in the development of academic learning behaviours (academic enablers) in children on the spectrum. This project addresses a gap in knowledge about the possible associations between anxiety and academic achievement in children on the spectrum. Understanding these associations opens up the possibility of new intervention pathways to enhance academic outcomes through anxiety reduction/prevention. METHODS: This longitudinal study will aim to recruit 64 children on the spectrum aged 4-5 years and their parents. Information will be gathered from children, parents and teachers. Children will be randomly assigned to one of two conditions in order to experimentally manipulate anxiety levels in the sample: experimental (to receive an anxiety reduction/prevention program, N = 32) or control (no intervention/treatment as usual, N = 32). The primary outcome measures are child academic skills and enabling behaviours assessed using the Academic Competence Evaluation Scales and the WIAT-II. Anxiety will be assessed through parent and teacher report. Assessments will be conducted at baseline, post-experimental manipulation of anxiety, and within the first year of formal schooling. It is hypothesised that anxiety will moderate the relationship between autism characteristics and academic enablers. DISSEMINATION: Results will be disseminated through peer-reviewed manuscripts and conference presentations. Lay summaries will be provided to all participants and available on the research centre website.

Lien vers le texte intégral (Open Access ou abonnement)

2. Avazzadeh S, Quinlan LR, Reilly J, McDonagh K, Jalali A, Wang Y, McInerney V, Krawczyk J, Ding Y, Fitzgerald J, O’Sullivan M, Forman EB, Lynch SA, Ennis S, Feerick N, Reilly R, Li W, Shen X, Yang G, Lu Y, Peeters H, Dockery P, O’Brien T, Shen S, Gallagher L. NRXN1α(+/-) is associated with increased excitability in ASD iPSC-derived neurons. BMC neuroscience. 2021; 22(1): 56.

BACKGROUND: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α(+/-) and showed increased calcium transients in patient neurons. METHODS: In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α(+/-) using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism. RESULTS: NRXN1α(+/-) cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α(+/-) cortical neurons. CONCLUSIONS: Together with recent evidence of increased calcium transients, our results showed that human NRXN1α(+/-) isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α(+/-) patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts.

Lien vers le texte intégral (Open Access ou abonnement)

3. Benkarim O, Paquola C, Park BY, Hong SJ, Royer J, Vos de Wael R, Lariviere S, Valk S, Bzdok D, Mottron L, B CB. Connectivity alterations in autism reflect functional idiosyncrasy. Communications biology. 2021; 4(1): 1078.

Autism spectrum disorder (ASD) is commonly understood as an alteration of brain networks, yet case-control analyses against typically-developing controls (TD) have yielded inconsistent results. Here, we devised a novel approach to profile the inter-individual variability in functional network organization and tested whether such idiosyncrasy contributes to connectivity alterations in ASD. Studying a multi-centric dataset with 157 ASD and 172 TD, we obtained robust evidence for increased idiosyncrasy in ASD relative to TD in default mode, somatomotor and attention networks, but also reduced idiosyncrasy in lateral temporal cortices. Idiosyncrasy increased with age and significantly correlated with symptom severity in ASD. Furthermore, while patterns of functional idiosyncrasy were not correlated with ASD-related cortical thickness alterations, they co-localized with the expression patterns of ASD risk genes. Notably, we could demonstrate that patterns of atypical idiosyncrasy in ASD closely overlapped with connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between inter-individual heterogeneity in autism and functional signatures. Our findings provide novel biomarkers to study atypical brain development and may consolidate prior research findings on the variable nature of connectome level anomalies in autism.

Lien vers le texte intégral (Open Access ou abonnement)

4. Borgolte A, Roy M, Sinke C, Wiswede D, Stephan M, Bleich S, Münte TF, Szycik GR. Enhanced attentional processing during speech perception in adult high-functioning autism spectrum disorder: An ERP-study. Neuropsychologia. 2021; 161: 108022.

Deficits in audiovisual speech perception have consistently been detected in patients with Autism Spectrum Disorder (ASD). Especially for patients with a highly functional subtype of ASD, it remains uncertain whether these deficits and underlying neural mechanisms persist into adulthood. Research indicates differences in audiovisual speech processing between ASD and healthy controls (HC) in the auditory cortex. The temporal dynamics of these differences still need to be characterized. Thus, in the present study we examined 14 adult subjects with high-functioning ASD and 15 adult HC while they viewed visual (lip movements) and auditory (voice) speech information that was either superimposed by white noise (condition 1) or not (condition 2). Subject’s performance was quantified by measuring stimulus comprehension. In addition, event-related brain potentials (ERPs) were recorded. Results demonstrated worse speech comprehension for ASD subjects compared to HC under noisy conditions. Moreover, ERP-analysis revealed significantly higher P2 amplitudes over parietal electrodes for ASD subjects compared to HC.

Lien vers le texte intégral (Open Access ou abonnement)

5. Brady NC, Kosirog C, Fleming K, Williams L. Predicting progress in word learning for children with autism and minimal verbal skills. Journal of neurodevelopmental disorders. 2021; 13(1): 36.

BACKGROUND: Approximately 30% of children diagnosed with autism remain minimally verbal past age 5. Interventions are often effective in increasing spoken communication for some of these children. Clinical and research decisions would be facilitated by identifying early indicators of progress in interventions. The purpose of this study was to investigate the relationship between speech sound measures obtained from the early phases of treatment and later treatment outcomes in children with autism and minimal verbal skills. METHODS: Twenty-three children (18 boys) between 5 and 9 years of age participated. We compared scores reflecting the phonemic features of word attempts produced during probes, and the number of correct words after 4 weeks of intervention to later word learning outcomes. RESULTS: Correlational and hierarchical regression analyses showed that both predictors were positively correlated with outcomes, but the phonemic scores were more strongly related than number of correct words. CONCLUSION: We conclude that phonemic scoring may be a useful measure to determine proximal gains in a spoken word learning intervention. Proximal measures are particularly helpful when trying to decide if the current course of intervention should be maintained or altered. TRIAL REGISTRATION: https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=2&cx=-jg9qo3 .

Lien vers le texte intégral (Open Access ou abonnement)

6. Cook KM, You X, Cherry JB, Merchant JS, Skapek M, Powers MD, Pugliese CE, Kenworthy L, Vaidya CJ. Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development. Journal of neurodevelopmental disorders. 2021; 13(1): 35.

BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity.

Lien vers le texte intégral (Open Access ou abonnement)

7. Corona LL, Stainbrook JA, Simcoe K, Wagner L, Fowler B, Weitlauf AS, Juárez AP, Warren Z. Utilization of telemedicine to support caregivers of young children with ASD and their Part C service providers: a comparison of intervention outcomes across three models of service delivery. Journal of neurodevelopmental disorders. 2021; 13(1): 38.

BACKGROUND: Families of young children with autism spectrum disorder (ASD) frequently experience barriers to accessing evidence-based early intervention services. Telemedicine presents an opportunity to increase access to these services, particularly for families in rural and under-resourced areas. The present article describes a brief behavioral intervention and support model for families of young children with concerns for ASD. In the context of the COVID-19 pandemic, this service model shifted to telemedicine-only service delivery, resulting in an opportunity to analyze intervention outcomes from services delivered either via traditional in-person visits, telemedicine-only sessions, or a hybrid model including both in-person and telemedicine sessions. METHODS: Data are presented for 115 families with toddlers 16-33 months of age who participated in a six-session behavioral intervention and support service model either in-person, through telemedicine, or through a hybrid service model. This intervention was available for families referred for ASD evaluation through the state Part C early intervention program. Intervention feasibility, fidelity of implementation, child outcomes, and stakeholder satisfaction are compared across service delivery models. RESULTS: Caregivers, behavioral consultants, and Part C early intervention providers reported satisfaction with services, regardless of service delivery model. Caregivers and consultants also reported positive child outcomes. Statistically significant differences emerged for caregiver- and consultant-reported child outcomes in some domains, with stakeholders in the telemedicine-only group reporting slightly less improvement, compared to stakeholders in the in-person-only group. Caregivers and consultants in the telemedicine-only group also provided qualitative feedback on benefits and challenges related to telemedicine services. CONCLUSIONS: Both caregivers and behavioral consultants reported positive outcomes following a brief behavioral intervention and support model targeted at families of young children with concern for ASD. Stakeholders reported improvement in child behavior and satisfaction with services across in-person, telemedicine-only, and hybrid models of service delivery. These results suggest that telemedicine presents a promising opportunity for increasing service access. Additional research is needed to continue optimizing the experience of telemedicine-based service delivery for both families and intervention providers.

Lien vers le texte intégral (Open Access ou abonnement)

8. Hards E, Loades ME, Higson-Sweeney N, Shafran R, Serafimova T, Brigden A, Reynolds S, Crawley E, Chatburn E, Linney C, McManus M, Borwick C. Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review. The British journal of clinical psychology. 2022; 61(2): 313-34.

OBJECTIVES: Periods of social isolation are associated with loneliness in children and young people, and loneliness is associated with poor mental and physical health. Children and young people with pre-existing mental health difficulties may be prone to loneliness. Containment of COVID-19 has necessitated widespread social isolation, with unprecedented school closures and restrictions imposed on social interactions. This rapid review aimed to establish what is known about the relationship between loneliness and mental health problems in children and young people with pre-existing mental health problems. METHODS: We sought to identify all primary research that examined the cross-sectional and longitudinal associations between loneliness/perceived social isolation and mental health in children and young people with pre-existing mental health problems. We also aimed to identify effective interventions that reduce the adverse impact of loneliness. A rapid systematic search was conducted using MEDLINE, PsycINFO, and Web of Science. RESULTS: Of 4,531 papers screened, 15 included children and young people with pre-existing mental health conditions. These 15 studies included 1,536 children and young people aged between 6 and 23 years with social phobia, anxiety and/or depression, and neurodevelopmental disorders. Loneliness was associated with anxiety and depression both cross-sectionally and prospectively in children and young people with mental health problems and neurodevelopmental conditions. We found preliminary evidence that psychological treatments can help to reduce feelings of loneliness in this population. CONCLUSIONS: Loneliness is associated with depression and anxiety in children and young people with pre-existing mental health conditions, and this relationship may be bidirectional. Existing interventions to address loneliness and/or mental health difficulties in other contexts may be applied to this population, although they may need adaptation and testing in younger children and adolescents. PRACTITIONER POINTS: Loneliness is common in children and young people, and during periods of enforced social isolation such as during COVID-19, children and young people report high levels of loneliness (or increased rates of loneliness). The review showed that loneliness is associated, both cross-sectionally and prospectively, in children and young people with mental health problems and also in children and young people with neurodevelopmental conditions, such as autism spectrum disorder. Thus, loneliness is a possible risk factor of which mental health providers should be aware. Maintaining social contact both by direct and by indirect means, especially through the Internet, could be important in mitigating loneliness. Interventions to address loneliness should be further developed and tested to help children and young people with pre-existing mental health problems who are lonely by preventing exacerbation of their mental health difficulties, in particular anxiety and depression.

Lien vers le texte intégral (Open Access ou abonnement)

9. Hoffman JM, Kirby AV. Parent Perspectives on Supports and Barriers for Autistic Youth Transitioning to Adulthood. Journal of autism and developmental disorders. 2021.

Knowledge is needed about specific supports and barriers for successful transitions to adulthood for autistic youth, especially from the perspective of parents, who are highly involved in transition preparation. We conducted a qualitative thematic analysis of previously conducted semi-structured interviews with 39 parents of 41 autistic adolescents to identify themes related to supports and barriers; we then used Bronfenbrenner’s Ecological System’s Theory to aid in interpreting the themes. We identified three main supports and four main barriers to the transition to adulthood from the parent interviews. The supports and barriers represent factors to consider at each theorized ecological level. Results point to opportunities to promote person-environment fit and support the transition to adulthood for autistic youth at multiple system levels.

Lien vers le texte intégral (Open Access ou abonnement)

10. Huang Y, Arnold SRC, Foley KR, Lawson LP, Richdale AL, Trollor JN. Factors associated with age at autism diagnosis in a community sample of Australian adults. Autism research : official journal of the International Society for Autism Research. 2021; 14(12): 2677-87.

Autism diagnosis in adulthood has become increasingly common due to a range of factors including changes in awareness, diagnostic criteria, and professional practices. Past research identified a range of demographic and autism-related factors associated with autism diagnosis age in children. However, it is unclear whether these apply to autistic adults. This study aimed to examine predictors of autism diagnosis age in adults while controlling for current age and autistic traits. We used a cross-sectional sample of 657 adults aged 15-80 from three self and carer-report studies: the Australian Longitudinal Study of Autism in Adulthood (ALSAA), Study of Australian School-Leavers with Autism (SASLA) and Pathways, Predictors and Impact of Receiving an Autism Spectrum Diagnosis in Adulthood (Pathways). Using hierarchical multiplicative heteroscedastic regression, we found that older current age and higher self-reported autistic traits predicted older diagnosis age, and that female gender, lack of intellectual disability, language other than English, family history of autism, lifetime depression, and no obsessive-compulsive disorder predicted older diagnosis age beyond current age and autistic traits. The paradoxical relationship between high autistic traits and older diagnosis age requires further investigation. Based on these findings, we recommended strategies to improve autism recognition in women and people from non-English-speaking backgrounds. Future studies could extend the findings by examining the effects of childhood and adulthood socioeconomic status on adult diagnosis age. LAY SUMMARY: We studied the relationship between age at autism diagnosis and other characteristics in adults. We found that both older current age and higher autistic traits, female gender, language other than English, family history of autism, and history of depression were related to older age at diagnosis, while intellectual disability and history of obsessive-compulsive disorder were related to younger age at diagnosis. Our findings suggest more work is needed to help recognize autism in women and people from non-English-speaking backgrounds.

Lien vers le texte intégral (Open Access ou abonnement)

11. Kim D, Lee JY, Jeong BC, Ahn JH, Kim JI, Lee ES, Kim H, Lee HJ, Han CE. Overconnectivity of the right Heschl’s and inferior temporal gyrus correlates with symptom severity in preschoolers with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2021; 14(11): 2314-29.

Previous studies have reported varying findings regarding the association of brain connectivity in autism spectrum disorder (ASD) with overconnectivity, underconnectivity, or both. Despite the emerging understanding that ASD is a developmental disconnection syndrome, very little is known about structural brain networks in preschool-aged children with low-functioning ASD. We aimed to investigate the structural brain connectivity of low-functioning ASD using diffusion magnetic resonance imaging and graph theory to examine alterations in different brain network topologies and identify any correlations with the clinical severity of ASD in preschool-aged children. Fifty-two preschool-aged children (28 with ASD and 24 with typical development) were included in the analysis. Graph-based network analysis was performed to examine the global and local structural brain networks. Nodal network measures exhibited increased nodal strength in the right Heschl’s gyrus, which was positively associated with all autistic clinical symptoms (Autism Diagnostic Observation Schedule and Childhood Autism Rating Scale [CARS]). The nodal strength of the right inferior temporal gyrus showed a moderate correlation with the CARS score. Using network-based statistics, we identified a subnetwork with increased connections encompassing the right Heschl’s gyrus and the right inferior temporal gyrus in preschool-aged children with ASD. The asymmetric value in the inferior temporal gyrus exhibited right dominance of nodal strength in children with ASD compared to that in typically developing children. Our findings support the theory of aberrant brain growth and overconnectivity as the underlying mechanism of ASD and provides new insights into potential regional biomarkers that can detect low-functioning ASD in preschool-aged children. LAY SUMMARY: This study supports the theory of aberrant brain growth and overconnectivity as an explanation for ASD. Measuring the right HG and inferior temporal gyrus provides new insights of potential regional biomarkers underpinning ASD in preschool-aged children.

Lien vers le texte intégral (Open Access ou abonnement)

12. Maye M, Boyd BA, Martínez-Pedraza F, Halladay A, Thurm A, Mandell DS. Biases, Barriers, and Possible Solutions: Steps Towards Addressing Autism Researchers Under-Engagement with Racially, Ethnically, and Socioeconomically Diverse Communities. Journal of autism and developmental disorders. 2021.

Autistic individuals who are also people of color or from lower socioeconomic strata are historically underrepresented in research. Lack of representation in autism research has contributed to health and healthcare disparities. Reducing these disparities will require culturally competent research that is relevant to under-resourced communities as well as collecting large nationally representative samples, or samples in which traditionally disenfranchised groups are over-represented. To achieve these goals, a diverse group of culturally competent researchers must partner with and gain the trust of communities to identify and eliminate barriers to participating in research. We suggest community-academic partnerships as one promising approach that results in high-quality research built on cultural competency, respect, and shared decision making.

Lien vers le texte intégral (Open Access ou abonnement)

13. McLaughlin CJ, Childress P, Armen SB, Allen SR. Adult Trauma Patients with Autism Spectrum Disorder: A Case-Control Study to Evaluate Disparities After Injury. Injury. 2021; 52(11): 3327-33.

BACKGROUND: Adult trauma patients with autism spectrum disorder (ASD) may have distinct care needs that have not been previously described. We hypothesized that due to differences in clinical care and disposition issues, injured adults with ASD would have increased lengths of stay, higher mortality, and increased rates of complications compared to adults without ASD. METHODS: The Pennsylvania Trauma Outcomes Study database was queried from 2010-2018 for trauma patients with ASD. Case-control matching was performed for two controls per ASD patient accounting for age, gender, injury mechanism, and injury severity score. Primary outcomes included length of stay, mortality, and complication rate. Univariate analysis compared presentation and clinical care between the two groups. Multivariate regression and Kaplan-Meier curves modeled length of stay. Significance was defined as p < 0.05. RESULTS: A total of 185 patients with ASD were matched to 370 controls. Age (mean +/- standard deviation) was 33.4 +/- 16.5 years. Gender was 81.1% male. Mechanisms were 88.1% blunt, 5.9% penetrating, and 5.9% burns. Significant clinical differences identified in patients with ASD vs. case-controls included presenting verbal GCS (median [IQR]) (5 [2] vs. 5 [0], p < 0.01), proportion of patients intubated at presentation (20.0% vs. 13.0%, p = 0.031), and hospital length of stay (4 [6] days vs. 3 [4] days, p = 0.002). Adult patients with ASD were less likely to be discharged home and more often discharged to a skilled nursing facility (p < 0.01). There were no differences in mortality, rates of complications, imaging, or operations. Multivariate regression analysis controlling for demographic and clinical differences revealed the diagnosis of ASD independently contributed 3.13 days (95% Confidence Interval: 1.85 to 4.41 days) to injured adults' length of stay. Kaplan-Meier curves showed injured patients with ASD were less likely to be discharged than case-controls starting from time of admission (log rank test, p < 0.001). CONCLUSIONS: This statewide analysis suggests injured patients with ASD have increased lengths of stay without other clinical or outcome differences. Given significant differences in discharge destination, these findings support early involvement of a multidisciplinary care collaborative. Further research is needed to identify factors that contribute to disparities in care for adults with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

14. Prillinger K, Radev ST, Amador de Lara G, Klöbl M, Lanzenberger R, Plener PL, Poustka L, Konicar L. Repeated Sessions of Transcranial Direct Current Stimulation on Adolescents With Autism Spectrum Disorder: Study Protocol for a Randomized, Double-Blind, and Sham-Controlled Clinical Trial. Frontiers in psychiatry. 2021; 12: 680525.

Background: Social-emotional difficulties are a core symptom of autism spectrum disorder (ASD). Accordingly, individuals with ASD have problems with social cognition such as recognizing emotions from other peoples’ faces. Various results from functional magnetic resonance imaging and electroencephalography studies as well as eye-tracking data reveal a neurophysiological basis of these deficits by linking them to abnormal brain activity. Thus, an intervention targeting the neural origin of ASD impairments seems warranted. A safe method able to influence neural activity is transcranial direct current stimulation (tDCS). This non-invasive brain stimulation method has already demonstrated promising results in several neuropsychiatric disorders in adults and children. The aim of this project is to investigate the effects of tDCS on ASD symptoms and their neural correlates in children and adolescents with ASD. Method: This study is designed as a double-blind, randomized, and sham-controlled trial with a target sample size of 20 male participants (aged 12-17 years) diagnosed with ASD. Before randomization, the participants will be stratified into comorbid depression, comorbid ADHS/conduct disorder, or no-comorbidity groups. The intervention phase comprises 10 sessions of anodal or sham tDCS applied over the left prefrontal cortex within 2 consecutive weeks. To engage the targeted brain regions, participants will perform a social cognition training during the stimulation. TDCS-induced effects on ASD symptoms and involved neural circuits will be investigated through psychological, neurophysiological, imaging, and behavioral data at pre- and post-measurements. Tolerability will be evaluated using a standardized questionnaire. Follow-up assessments 1 and 6 months after the intervention will examine long-lasting effects. Discussion: The results of this study will provide insights into the changeability of social impairments in ASD by investigating social and emotional abilities on different modalities following repeated sessions of anodal tDCS with an intra-simulation training. Furthermore, this trial will elucidate the tolerability and the potential of tDCS as a new treatment approach for ASD in adolescents. Clinical Trial Registration: The study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS00017505) on 02/07/2019.

Lien vers le texte intégral (Open Access ou abonnement)

15. Roberts TPL, Kuschner ES, Edgar JC. Biomarkers for autism spectrum disorder: opportunities for magnetoencephalography (MEG). Journal of neurodevelopmental disorders. 2021; 13(1): 34.

This paper reviews a candidate biomarker for ASD, the M50 auditory evoked response component, detected by magnetoencephalography (MEG) and presents a position on the roles and opportunities for such a biomarker, as well as converging evidence from allied imaging techniques (magnetic resonance imaging, MRI and spectroscopy, MRS). Data is presented on prolonged M50 latencies in ASD as well as extension to include children with ASD with significant language and cognitive impairments in whom M50 latency delays are exacerbated. Modeling of the M50 latency by consideration of the properties of auditory pathway white matter is shown to be successful in typical development but challenged by heterogeneity in ASD; this, however, is capitalized upon to identify a distinct subpopulation of children with ASD whose M50 latencies lie well outside the range of values predictable from the typically developing model. Interestingly, this subpopulation is characterized by low levels of the inhibitory neurotransmitter GABA. Following from this, we discuss a potential use of the M50 latency in indicating « target engagement » acutely with administration of a GABA-B agonist, potentially distinguishing « responders » from « non-responders » with the implication of optimizing inclusion for clinical trials of such agents. Implications for future application, including potential evaluation of infants with genetic risk factors, are discussed. As such, the broad scope of potential of a representative candidate biological marker, the M50 latency, is introduced along with potential future applications.This paper outlines a strategy for understanding brain dysfunction in individuals with intellectual and developmental disabilities (IDD). It is proposed that a multimodal approach (collection of brain structure, chemistry, and neuronal functional data) will identify IDD subpopulations who share a common disease pathway, and thus identify individuals with IDD who might ultimately benefit from specific treatments. After briefly demonstrating the need and potential for scope, examples from studies examining brain function and structure in children with autism spectrum disorder (ASD) illustrate how measures of brain neuronal function (from magnetoencephalography, MEG), brain structure (from magnetic resonance imaging, MRI, especially diffusion MRI), and brain chemistry (MR spectroscopy) can help us better understand the heterogeneity in ASD and form the basis of multivariate biological markers (biomarkers) useable to define clinical subpopulations. Similar approaches can be applied to understand brain dysfunction in neurodevelopmental disorders (NDD) in general. In large part, this paper represents our endeavors as part of the CHOP/Penn NICHD-funded intellectual and developmental disabilities research center (IDDRC) over the past decade.

Lien vers le texte intégral (Open Access ou abonnement)

16. Salim S, Banu A, Alwa A, Gowda SBM, Mohammad F. The gut-microbiota-brain axis in autism: what Drosophila models can offer?. Journal of neurodevelopmental disorders. 2021; 13(1): 37.

The idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Shilpa O, Anupama KP, Antony A, Gurushankara HP. Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster. Molecular neurobiology. 2021; 58(12): 6378-93.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis.Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner.Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

Lien vers le texte intégral (Open Access ou abonnement)

18. Shiota Y, Matsudaira I, Takeuchi H, Ono C, Tomita H, Kawashima R, Taki Y. The influence of NRXN1 on systemizing and the brain structure in healthy adults. Brain imaging and behavior. 2022; 16(2): 692-701.

Certain behavioral characteristics of autism spectrum disorder can be found in otherwise healthy people. Individuals with difficulties in social adaptation may have subclinical autistic traits; however, effective biomarkers of these traits have not yet been established. There is a dire need for objective indices of these traits that combine behavior, brain images, and genetic information. In this study, we examined the association among a single nucleotide polymorphism of NRXN1 (rs858932; C/G), autistic traits, and brain structure in 311 healthy adults. We found that carriers of minor alleles (carriers of the G-allele) had significantly higher systemizing scores than major-allele (C-allele) homozygotes. Furthermore, the regional white matter volume in the right anterior limb of the internal capsule was significantly greater in carriers of the G-allele than in C-allele homozygotes. To the best of our knowledge, this is the first report of NRXN1 rs858932 being involved in systemizing and the brain structure of healthy adults. Our findings provide insight into the effects of genetics on autistic traits and their respective neural substrates.

Lien vers le texte intégral (Open Access ou abonnement)

19. Svancara AM, Kana R, Bednarz H, Sherrod G, Visscher K, McManus B, Stavrinos D. Time-to-Collision Estimations in Young Drivers with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Journal of autism and developmental disorders. 2021.

Individuals with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) may exhibit driving difficulties due to cognitive impairments such as time perception difficulties, a construct related to the perception of time-to-collision (TTC). This study examined the timing abilities of drivers with ASD and ADHD. Sixty participants (n(ADHD) = 20, n(ASD) = 20, n(TD) = 20) completed a time reproduction task and a TTC estimation task in a driving simulator. Results indicated drivers with ASD were less precise in time reproduction across all time intervals and over-reproduced time at shorter intervals. Drivers with ASD produced larger TTC estimates when driving at a faster speed compared to typically developing drivers. Drivers with ASD, but not ADHD, appear to present difficulties in time estimation abilities.

Lien vers le texte intégral (Open Access ou abonnement)

20. Tan DW, Gilani SZ, Boutrus M, Alvares GA, Whitehouse AJO, Mian A, Suter D, Maybery MT. Facial asymmetry in parents of children on the autism spectrum. Autism research : official journal of the International Society for Autism Research. 2021; 14(11): 2260-9.

Greater facial asymmetry has been consistently found in children with autism spectrum disorder (ASD) relative to children without ASD. There is substantial evidence that both facial structure and the recurrence of ASD diagnosis are highly heritable within a nuclear family. Furthermore, sub-clinical levels of autistic-like behavioural characteristics have also been reported in first-degree relatives of individuals with ASD, commonly known as the ‘broad autism phenotype’. Therefore, the aim of the current study was to examine whether a broad autism phenotype expresses as facial asymmetry among 192 biological parents of autistic individuals (134 mothers) compared to those of 163 age-matched adults without a family history of ASD (113 females). Using dense surface-modelling techniques on three dimensional facial images, we found evidence for greater facial asymmetry in parents of autistic individuals compared to age-matched adults in the comparison group (p = 0.046, d = 0.21 [0.002, 0.42]). Considering previous findings and the current results, we conclude that facial asymmetry expressed in the facial morphology of autistic children may be related to heritability factors. LAY ABSTRACT: In a previous study, we showed that autistic children presented with greater facial asymmetry than non-autistic children. In the current study, we examined the amount of facial asymmetry shown on three-dimensional facial images of 192 parents of autistic children compared to a control group consisting of 163 similarly aged adults with no known history of autism. Although parents did show greater levels of facial asymmetry than those in the control group, this effect is statistically small. We concluded that the facial asymmetry previously found in autistic children may be related to genetic factors.

Lien vers le texte intégral (Open Access ou abonnement)

21. Watanabe S, Kurotani T, Oga T, Noguchi J, Isoda R, Nakagami A, Sakai K, Nakagaki K, Sumida K, Hoshino K, Saito K, Miyawaki I, Sekiguchi M, Wada K, Minamimoto T, Ichinohe N. Functional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease. Nature communications. 2021; 12(1): 5388.

Autism spectrum disorder (ASD) is a multifactorial disorder with characteristic synaptic and gene expression changes. Early intervention during childhood is thought to benefit prognosis. Here, we examined the changes in cortical synaptogenesis, synaptic function, and gene expression from birth to the juvenile stage in a marmoset model of ASD induced by valproic acid (VPA) treatment. Early postnatally, synaptogenesis was reduced in this model, while juvenile-age VPA-treated marmosets showed increased synaptogenesis, similar to observations in human tissue. During infancy, synaptic plasticity transiently increased and was associated with altered vocalization. Synaptogenesis-related genes were downregulated early postnatally. At three months of age, the differentially expressed genes were associated with circuit remodeling, similar to the expression changes observed in humans. In summary, we provide a functional and molecular characterization of a non-human primate model of ASD, highlighting its similarity to features observed in human ASD.

Lien vers le texte intégral (Open Access ou abonnement)

22. Yalçintepe S, Görker I, Demir S, Atli E, Atli E, Tozkir H, Süt N, Özen Y, Eker D, Mail Ç, Güler HS, Zhuri D, Gurkan H. Investigation the Relationship of Autism Spectrum Disorder and FOXP2, GRIN2B, KATNAL2, GABRA4 Genes. Noro psikiyatri arsivi. 2021; 58(3): 171-5.

INTRODUCTION: Autism spectrum disorder is a genetically and phenotypically heterogeneous group. Genetic studies carried out to date have suggested that both common and rare genetic variants play a role in the etiology of this disorder. In our study, we aimed to investigate the effect of FOXP2, GRIN2B, KATNAL2 and GABRA4 gene variants in the pathogenesis of autism spectrum disorder. METHOD: In our prospectively planned study, all exons and exon-intron junctions of FOXP2, GRIN2B, KATNAL2 and GABRA4 genes were screened by next generation sequencing analysis in 96 patients who diagnosed with autism spectrum disorder. RESULTS: In our study, the average age was 10.1 and the male/female ratio was 75/21. Pathogenic or likely pathogenic variants were not detected in FOXP2, GRIN2B, KATNAL2 and GABRA4 genes, however, 69 intronic variants of unknown clinical significance were detected in 50 cases (52%). Among those, 26 were in the GABRA4 gene, 22 in the FOXP2 gene, 13 in the KATNAL2 gene, and 8 in the GRIN2B gene. Twenty three of these 69 variants were novel that were not previously reported in the literature. CONCLUSION: In our study, we could not identify a relationship between the autism spectrum disorder and FOXP2, GRIN2B, KATNAL2 and GABRA4 genes. Identifying genetic risk factors that play a role in the etiopathogenesis of autism spectrum disorder will contribute significantly to understanding the molecular mechanisms of the disease and the development of new treatment strategies. In this context, comprehensive molecular genetic studies such as whole exome or whole genome sequencing are required with higher number of cases in different populations.

Lien vers le texte intégral (Open Access ou abonnement)