1. Ahn YA, Moffitt JM, Tao Y, Custode S, Parlade M, Beaumont A, Cardona S, Hale M, Durocher J, Alessandri M, Shyu ML, Perry LK, Messinger DS. Objective Measurement of Social Gaze and Smile Behaviors in Children with Suspected Autism Spectrum Disorder During Administration of the Autism Diagnostic Observation Schedule, 2nd Edition. Journal of autism and developmental disorders. 2023.

Best practice for the assessment of autism spectrum disorder (ASD) symptom severity relies on clinician ratings of the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2), but the association of these ratings with objective measures of children’s social gaze and smiling is unknown. Sixty-six preschool-age children (49 boys, M = 39.97 months, SD = 10.58) with suspected ASD (61 confirmed ASD) were administered the ADOS-2 and provided social affect calibrated severity scores (SA CSS). Children’s social gaze and smiling during the ADOS-2, captured with a camera contained in eyeglasses worn by the examiner and parent, were obtained via a computer vision processing pipeline. Children who gazed more at their parents (p = .04) and whose gaze at their parents involved more smiling (p = .02) received lower social affect severity scores, indicating fewer social affect symptoms, adjusted R(2) = .15, p = .003.

Lien vers le texte intégral (Open Access ou abonnement)

2. Amat AZ, Adiani D, Tauseef M, Breen M, Hunt S, Swanson A, Weitlauf AS, Warren ZE, Sarkar N. Design of a Desktop Virtual Reality-based Collaborative Activities Simulator (ViRCAS) to Support Teamwork in Workplace Settings for Autistic Adults. IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society. 2023; Pp.

Autistic adults possess many skills sought by employers, but may be at a disadvantage in the workplace if social-communication differences negatively impact teamwork. We present a novel collaborative virtual reality (VR)-based activities simulator, called ViRCAS, that allows autistic and neurotypical adults to work together in a shared virtual space, offering the chance to practice teamwork and assess progress. ViRCAS has three main contributions: 1) a new collaborative teamwork skills practice platform; 2) a stakeholder-driven collaborative task set with embedded collaboration strategies; and 3) a framework for multimodal data analysis to assess skills. Our feasibility study with 12 participant pairs showed preliminary acceptance of ViRCAS, a positive impact of the collaborative tasks on supported teamwork skills practice for autistic and neurotypical individuals, and promising potential to quantitatively assess collaboration through multimodal data analysis. The current work paves the way for longitudinal studies that will assess whether the collaborative teamwork skill practice that ViRCAS provides also contributes towards improved task performance.

Lien vers le texte intégral (Open Access ou abonnement)

3. Anggadiredja K, Fisheri Kurniati N, Kasai A, Hashimoto H. Decreased Expression of EP3 Receptor mRNA in the Brain of Mouse Model of Autism Spectrum Disorder. MicroRNA (Shariqah, United Arab Emirates). 2023.

BACKGROUND: Accumulating evidence has implicated the role of neuroinflammation in the pathology of autism spectrum disorder (ASD), a neurodevelopmental disorder. OBJECTIVES: To investigate the expression of prostaglandin EP3 (EP3) receptor mRNA in the brain of ASD mice model. METHODS: Pregnant mice were injected with valproic acid (VPA) 500 mg/kg intraperitoneally at 12.5 d gestation. The offspring were tested at the age of 5-6 weeks old for their social interaction behavior. Each mouse was assessed for prostaglandin EP3 receptor expression in the prefrontal cortical, hippocampal and cerebellar areas one day after the behavioral test. RESULTS: Compared to the naive, mice born to dams treated with VPA demonstrated a significantly shorter duration of sniffing behavior, a model of social interaction. Results further showed that the expression of EP3 receptor mRNA was significantly lower in all three brain regions of the mice born to VPA-treated dams. CONCLUSION: The present study provides further evidence of the relevance of the arachidonic acid cascade as an essential part of neuroinflammation in the pathology of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

4. Apte M, Kumar A. Correlation of mutated gene and signalling pathways in ASD. IBRO neuroscience reports. 2023; 14: 384-92.

Autism is a complicated spectrum of neurodevelopmental illnesses characterized by repetitive and constrained behaviors and interests, as well as social interaction and communication difficulties that are first shown in infancy. More than 18 million Indians, according to the National Health Portal of India, and 1 in 160 children worldwide, according to the WHO, are diagnosed with autism spectrum disorders. This review aims to discuss the complex genetic architecture that underlies autism and summarizes the role of proteins likely to play in the development of autism. We also consider how genetic mutations can affect convergent signaling pathways and hinder the development of brain circuitry and the role of cognition development and theory of mind with Cognition-behavior therapy benefits in autism.

Lien vers le texte intégral (Open Access ou abonnement)

5. Asif M, Martiniano H, Lamurias A, Kausar S, Couto FM. DGH-GO: dissecting the genetic heterogeneity of complex diseases using gene ontology. BMC bioinformatics. 2023; 24(1): 171.

BACKGROUND: Complex diseases such as neurodevelopmental disorders (NDDs) exhibit multiple etiologies. The multi-etiological nature of complex-diseases emerges from distinct but functionally similar group of genes. Different diseases sharing genes of such groups show related clinical outcomes that further restrict our understanding of disease mechanisms, thus, limiting the applications of personalized medicine approaches to complex genetic disorders. RESULTS: Here, we present an interactive and user-friendly application, called DGH-GO. DGH-GO allows biologists to dissect the genetic heterogeneity of complex diseases by stratifying the putative disease-causing genes into clusters that may contribute to distinct disease outcome development. It can also be used to study the shared etiology of complex-diseases. DGH-GO creates a semantic similarity matrix for the input genes by using Gene Ontology (GO). The resultant matrix can be visualized in 2D plots using different dimension reduction methods (T-SNE, Principal component analysis, umap and Principal coordinate analysis). In the next step, clusters of functionally similar genes are identified from genes functional similarities assessed through GO. This is achieved by employing four different clustering methods (K-means, Hierarchical, Fuzzy and PAM). The user may change the clustering parameters and explore their effect on stratification immediately. DGH-GO was applied to genes disrupted by rare genetic variants in Autism Spectrum Disorder (ASD) patients. The analysis confirmed the multi-etiological nature of ASD by identifying four clusters of genes that were enriched for distinct biological mechanisms and clinical outcome. In the second case study, the analysis of genes shared by different NDDs showed that genes causing multiple disorders tend to aggregate in similar clusters, indicating a possible shared etiology. CONCLUSION: DGH-GO is a user-friendly application that allows biologists to study the multi-etiological nature of complex diseases by dissecting their genetic heterogeneity. In summary, functional similarities, dimension reduction and clustering methods, coupled with interactive visualization and control over analysis allows biologists to explore and analyze their datasets without requiring expert knowledge on these methods. The source code of proposed application is available at https://github.com/Muh-Asif/DGH-GO.

Lien vers le texte intégral (Open Access ou abonnement)

6. Bonete S, Molinero C, Ruisanchez D. Emotional Dysfunction and Interoceptive Challenges in Adults with Autism Spectrum Disorders. Behavioral sciences (Basel, Switzerland). 2023; 13(4).

People with autism spectrum disorder (ASD) frequently show impaired sensory processing in different senses, including the interoceptive system. Recent findings suggest that interoception is a fundamental component of emotional experience and that impaired interoception is associated with alexithymia. This study aims to explore the association and interrelation between interoceptive confusion, alexithymia, and the capacity for emotional regulation among a sample of 33 adults with ASD compared to a control group of 35 adults with neurotypical development and its mutual impact. The participants answered a series of questionnaires addressing these three variables. The results showed (1) significant differences between the groups in all dimensions, with dysfunctional emotional regulation, impaired interoception, and alexithymia in the ASD group, (2) significant correlations between interoceptive confusion, emotional clarity, and alexithymia in the ASD group but only positive correlations between interoceptive confusion and alexithymia in the CG, and (3) that emotional clarity, alexithymia, and autism explain 61% of the variance in interoceptive confusion. These results are in line with previous studies and suggest that training interoceptive ability may enhance emotional clarity and reduce alexithymia among those diagnosed with ASD, with significant implications in the planning of treatment.

Lien vers le texte intégral (Open Access ou abonnement)

7. Carter EW, Lanchak ER, Guest L, McMillan ED, Taylor JL, Fleming LP, Dao A. Family Perspectives on the Complexities of Pursuing Integrated Employment for Adults With Intellectual and Developmental Disabilities. American journal on intellectual and developmental disabilities. 2023; 128(3): 219-36.

The road to employment is not often easy for individuals with intellectual and developmental disabilities (IDD). Families know firsthand the complexities and challenges of obtaining employment for their members with extensive support needs. The purpose of this qualitative study was to identify the critical barriers they encounter in this important pursuit. We interviewed 60 parents (and other caregivers) whose family members with intellectual disability and/or autism had sought and/or obtained paid work. The difficulties they described were extensive and multifaceted. Specifically, participants identified 64 different barriers attributed to six primary areas: individuals, families, schools, service systems, workplaces, and communities. Their unique insights amplify the need for new approaches for promoting integrated employment. We offer recommendations for research and practice aimed at better understanding and ameliorating barriers to meaningful work for adults with IDD.

Lien vers le texte intégral (Open Access ou abonnement)

8. Chakrabarti B. Autism in India: Time for a national programme. The Indian journal of medical research. 2023.

Lien vers le texte intégral (Open Access ou abonnement)

9. Dembo RS, Hong J, DaWalt LS, Berry-Kravis EM, Mailick MR. Health Effects of Sleep Quality in Premutation Carrier Mothers of Individuals With Fragile X Syndrome. American journal on intellectual and developmental disabilities. 2023; 128(3): 254-68.

Sleep plays an integral role in supporting well-being, and sleep difficulties are common in mothers of individuals with developmental disabilities, including fragile X syndrome (FXS). This study assessed whether the effects of sleep quality on physical health and depression are exacerbated by genetic risk factors (CGG repeats) in FMR1 premutation carrier mothers of individuals with FXS. Poor sleep quality predicted a greater number of physical health conditions for mothers with CGG repeats in the mid-premutation range (90-110 repeats), but not for those in the lower (< 90 repeats) or higher (> 110 repeats) ends of the range. A significant association between poor sleep quality and maternal depressive symptoms was also observed, but there was no evidence that this effect varied by level of genetic vulnerability. This research extends our understanding of individual differences in the effects of sleep quality among mothers of individuals with FXS.

Lien vers le texte intégral (Open Access ou abonnement)

10. Dong L, Wang Y, Wang X, Luo T, Zhou Q, Zhao G, Li B, Xia L, Xia K, Li J. Interactions of genetic risks for autism and the broad autism phenotypes. Frontiers in psychiatry. 2023; 14: 1110080.

BACKGROUND: Common polygenic risk and de novo variants (DNVs) capture a small proportion of autism spectrum disorder (ASD) liability, and ASD phenotypic heterogeneity remains difficult to explain. Integrating multiple genetic factors contribute to clarifying the risk and clinical presentation of ASD. METHODS: In our study, we investigated the individual and combined effects of polygenic risk, damaging DNVs (including those in ASD risk genes), and sex among 2,591 ASD simplex families in the Simons Simplex Collection. We also explored the interactions among these factors, along with the broad autism phenotypes of ASD probands and their unaffected siblings. Finally, we combined the effects of polygenic risk, damaging DNVs in ASD risk genes, and sex to explain the total liability of ASD phenotypic spectrum. RESULTS: Our findings revealed that both polygenic risk and damaging DNVs contribute to an increased risk for ASD, with females exhibiting higher genetic burdens than males. ASD probands that carry damaging DNVs in ASD risk genes showed reduced polygenic risk. The effects of polygenic risk and damaging DNVs on autism broad phenotypes were inconsistent; probands with higher polygenic risk exhibited improvement in some behaviors, such as adaptive/cognitive behaviors, while those with damaging DNVs exhibited more severe phenotypes. Siblings with higher polygenic risk and damaging DNVs tended to have higher scores on broader autism phenotypes. Females exhibited more severe cognitive and behavioral problems compared to males among both ASD probands and siblings. The combination of polygenic risk, damaging DNVs in ASD risk genes, and sex explained 1-4% of the total liability of adaptive/cognitive behavior measurements. CONCLUSION: Our study revealed that the risk for ASD and the autism broad phenotypes likely arises from a combination of common polygenic risk, damaging DNVs (including those in ASD risk genes), and sex.

Lien vers le texte intégral (Open Access ou abonnement)

11. Feinberg JI, Schrott R, Ladd-Acosta C, Newschaffer CJ, Hertz-Picciotto I, Croen LA, Daniele Fallin M, Feinberg AP, Volk HE. Epigenetic changes in sperm are associated with paternal and child quantitative autistic traits in an autism-enriched cohort. Molecular psychiatry. 2023.

There is a need to consider paternal contributions to autism spectrum disorder (ASD) more strongly. Autism etiology is complex, and heritability is not explained by genetics alone. Understanding paternal gametic epigenetic contributions to autism could help fill this knowledge gap. In the present study, we explored whether paternal autistic traits, and the sperm epigenome, were associated with autistic traits in children at 36 months enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is a pregnancy cohort that recruited and enrolled pregnant women in the first half of pregnancy who already had a child with ASD. After maternal enrollment, EARLI fathers were approached and asked to provide a semen specimen. Participants were included in the present study if they had genotyping, sperm methylation data, and Social Responsiveness Scale (SRS) score data available. Using the CHARM array, we performed genome-scale methylation analyses on DNA from semen samples contributed by EARLI fathers. The SRS-a 65-item questionnaire measuring social communication deficits on a quantitative scale-was used to evaluate autistic traits in EARLI fathers (n = 45) and children (n = 31). We identified 94 significant child SRS-associated differentially methylated regions (DMRs), and 14 significant paternal SRS-associated DMRs (fwer p < 0.05). Many child SRS-associated DMRs were annotated to genes implicated in ASD and neurodevelopment. Six DMRs overlapped across the two outcomes (fwer p < 0.1), and, 16 DMRs overlapped with previous child autistic trait findings at 12 months of age (fwer p < 0.05). Child SRS-associated DMRs contained CpG sites independently found to be differentially methylated in postmortem brains of individuals with and without autism. These findings suggest paternal germline methylation is associated with autistic traits in 3-year-old offspring. These prospective results for autism-associated traits, in a cohort with a family history of ASD, highlight the potential importance of sperm epigenetic mechanisms in autism.

Lien vers le texte intégral (Open Access ou abonnement)

12. Friedman S, Noble R, Archer S, Gibson J, Hughes C. Respite and connection: Autistic adults’ reflections upon nature and well-being during the Covid-19 pandemic. Autism : the international journal of research and practice. 2023: 13623613231166462.

The Covid-19 pandemic and associated lockdowns provided opportunities to spend time in nature, with many people reporting that this benefitted their well-being. However, existing research from the pandemic period has focused on the way general populations experienced nature; less is known about how autistic people used nature to support their well-being during the pandemic. We created a survey that invited autistic adults living in the United Kingdom to reply to text box questions. A total of 127 people responded to our survey; we analysed their responses using a method called reflexive thematic analysis and developed themes based on patterns among all the responses. We developed two themes: respite in nature and connecting amid widespread disconnection. For some autistic adults during the pandemic, nature provided physical distance from others or from crowded homes, which helped them reduce their stress. In addition, some participants felt more psychologically connected to nature itself during the pandemic, while for others, nature served as a way of connecting with others during a potentially isolating time. These findings are important for autistic people and their families and carers who may want to seek out nature-based activities to support well-being in the wake of the pandemic.

Lien vers le texte intégral (Open Access ou abonnement)

13. Gao S, Wang X, Su Y. Examining whether adults with autism spectrum disorder encounter multiple problems in theory of mind: a study based on meta-analysis. Psychonomic bulletin & review. 2023.

Theory of mind (ToM) represents a complex ability, while persons with autism spectrum disorder (ASD) encounter difficulties in the processing of ToM. The present ToM-focused studies on adults with ASD report inconsistent results, possibly owing to the differences between tasks. For instance, different ToM-related tasks involve different cognitive abilities, but the development of these cognitive abilities is different among adults with ASD, thereby leading to different behaviors by the same individual with ASD in different tasks. Therefore, it is of vital significance to explore the potential reasons for inconsistencies in the existing studies based on the task classification perspective. Hence, this study primarily reviews the existing ToM tasks used in studies on adults with ASD; afterward, based on the forms and characteristics of the task, the current ToM tasks are classified into four categories-reading comprehension, perceptual scene comprehension, comprehensive scene comprehension , and self-other processing. Subsequently, a meta-analysis is undertaken to determine the difference in each ToM task category between the ASD group and the typically developing (TD) group. As a result, 110 research papers (including 3,205 adults with ASD and 3,675 TD adults) that fulfilled the stated criteria are examined in this study. The study findings suggest that adults with ASD demonstrate worse performance in terms of all four ToM task categories as compared to TD adults. Furthermore, compared with tasks of self-other processing and perceptual scene comprehension, adults with ASD perform worse in reading comprehension and comprehensive scene comprehension. This shows that the differences between tasks may exert a potential influence on the study results. Future studies should focus on different abilities involved in ToM processing and the choice of ToM tasks, in order to elucidate the critical problems of ToM in adults with ASD.

Lien vers le texte intégral (Open Access ou abonnement)

14. Girard D, Courchesne V, Cimon-Paquet C, Jacques C, Soulières I. Visual abilities and exploration behaviors as predictors of intelligence in autistic children from preschool to school age. Autism : the international journal of research and practice. 2023: 13623613231166189.

At the time of diagnosis, parents of autistic children frequently wonder what the future holds for their children in terms of intellectual development. It remains however difficult to answer this question at such a young age. Indeed, while early precursors of intelligence are well known for children following a typical development, these precursors remain to be identified for autistic children. Some theoretical models of intelligence suggest that perceptual abilities or behaviors, as seen early in autistic cognitive development, could be early indicators of intelligence. However, research examining the relation between early perceptual predictors and autistic intelligence over time is needed. This article is the first to consider a variety of early perceptual abilities and behaviors as precursors/predictors of intelligence at school age in autistic children. We showed that better performance in perceptual tasks at preschool age predicted better intellectual abilities measured later in autistic children. Importantly, our sample of autistic children represented the whole spectrum, including children with few to no spoken words, who are an important proportion of autistic preschoolers. While early perceptual abilities and behaviors may not substitute for a formal intellectual assessment, our results support that these indices may help estimate later intellectual level in autistic children. Perceptual abilities have the advantage to be easy to observe at preschool age and seem to fit the cognitive style of autistic children. Assessment methods could probably gain from including and focusing more on the perceptual strengths of autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

15. Justus SA, Mirjalili S, Powell PS, Duarte A. Neural reinstatement of context memory in adults with autism spectrum disorder. Cerebral cortex (New York, NY : 1991). 2023.

Autism spectrum disorder (ASD) is associated with episodic memory impairment. However, episodic memories include a variety of contextual details, and it is difficult to solely rely on behavioral data to assess how specifically (i.e. event-specific reinstatement) an event is remembered. We applied encoding-retrieval representational similarity (ERS) analysis to EEG data to assess event-specific ERS for object-context associations in a sample of 34 adults (17 with, 17 without ASD). Participants studied objects presented alongside 2 contextual features: scene/color, and attention was directed toward one object-context relationship. At retrieval, memory was assessed for the object and both contexts. Behavioral results revealed no group differences in item or context memory performance. ERS results revealed group temporal differences in reinstatement. Results may indicate differences in both encoding (i.e. fewer perceptual details) and retrieval (i.e. ineffectively skipping through memory fragments) in ASD and should be further investigated in studies modulating the perceptual detail required for memory decisions. Results highlight the utility of ERS as a methodology used to evaluate episodic reinstatement even in the absence of behavioral differences in memory performance.

Lien vers le texte intégral (Open Access ou abonnement)

16. Kasten K, Jacoby N, Ahissar M. Poor synchronization yet adequate tempo-keeping in adults with autism. Autism research : official journal of the International Society for Autism Research. 2023.

Sensorimotor synchronization to external events is fundamental to social interactions. Adults with autism spectrum condition (ASC) have difficulty with synchronization, manifested in both social and non-social situations, such as paced finger-tapping tasks, where participants synchronize their taps to metronome beats. What limits ASC’s synchronization is a matter of debate, especially whether it stems from reduced online correction of synchronization error (the « slow update » account) or from noisy internal representations (the « elevated internal noise » account). To test these opposing theories, we administered a synchronization-continuation tapping task, with and without tempo changes. Participants were asked to synchronize with the metronome and continue the tempo when it stopped. Since continuation is based only on internal representations, the slow update hypothesis predicts no difficulty, whereas the elevated noise hypothesis predicts similar or enhanced difficulties. Additionally, tempo changes were introduced, to assess whether adequate updating of internal representations to external changes is possible when given a longer temporal window for updating. We found that the ability to keep the metronome’s tempo after it stopped did not differ between ASC and typically developing (TD) individuals. Importantly, when given a longer period to adapt to external changes, keeping a modified tempo was also similar in ASC. These results suggest that synchronization difficulties in ASC stem from slow update rather than elevated internal noise.

Lien vers le texte intégral (Open Access ou abonnement)

17. Kourtesis P, Kouklari EC, Roussos P, Mantas V, Papanikolaou K, Skaloumbakas C, Pehlivanidis A. Virtual Reality Training of Social Skills in Adults with Autism Spectrum Disorder: An Examination of Acceptability, Usability, User Experience, Social Skills, and Executive Functions. Behavioral sciences (Basel, Switzerland). 2023; 13(4).

Poor social skills in autism spectrum disorder (ASD) are associated with reduced independence in daily life. Current interventions for improving the social skills of individuals with ASD fail to represent the complexity of real-life social settings and situations. Virtual reality (VR) may facilitate social skills training in social environments and situations similar to those in real life; however, more research is needed to elucidate aspects such as the acceptability, usability, and user experience of VR systems in ASD. Twenty-five participants with ASD attended a neuropsychological evaluation and three sessions of VR social skills training, which incorporated five social scenarios with three difficulty levels. Participants reported high acceptability, system usability, and user experience. Significant correlations were observed between performance in social scenarios, self-reports, and executive functions. Working memory and planning ability were significant predictors of the functionality level in ASD and the VR system’s perceived usability, respectively. Yet, performance in social scenarios was the best predictor of usability, acceptability, and functionality level. Planning ability substantially predicted performance in social scenarios, suggesting an implication in social skills. Immersive VR social skills training in individuals with ASD appears to be an appropriate service, but an errorless approach that is adaptive to the individual’s needs should be preferred.

Lien vers le texte intégral (Open Access ou abonnement)

18. Larson EA. 5Minutes4Myself: Development of a Wellness Program for Caregivers of Children with Autism. Canadian journal of occupational therapy Revue canadienne d’ergotherapie. 2023: 84174231172036.

Background. Many caregivers of autistic children experience increased stress, and diminished health often due to the caregiving demands. Purpose. The project aim was to design a feasible and sustainable wellness program tailored to these caregivers’ lives. Methods. In this collaborative research-informed project, participants (N = 28) were mostly female, white, and well-educated. In focus groups, we delineated lifestyle issues, then designed, delivered and assessed an initial program with one cohort; and repeated this process with a second group. Findings. Focus group data were transcribed then coded qualitatively to inform following steps. Data analysis identified lifestyle issues key to program design, desired program elements, and after program delivery, affirmed elements and recommended changes. The team used meta-inferences to guide program revisions after each cohort. Implications. Caregivers viewed resulting 5Minutes4Myself program as filling a significant service gap; its hybrid design used in-person coaching and a habit-building app with mindfulness content to support lifestyle change.

Lien vers le texte intégral (Open Access ou abonnement)

19. Lyu Y, Song F, Zhang K, Gao M, Ma J, Wang D, Wan Y, Liu Y, Gai Z. [Clinical characteristics and genetic analysis of two children with Autosomal dominant mental retardation type 21 due to variants of CTCF gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2023; 40(5): 543-6.

OBJECTIVE: To explore the clinical and genetic characteristics of two children with developmental delay. METHODS: Two children who had presented at the Children’s Hospital Affiliated to Shandong University on August 18, 2021 were enrolled as the study subjects. Clinical and laboratory examination, chromosomal karyotyping and high-throughput sequencing were carried out for both children. RESULTS: Both children had a 46,XX karyotype. High-throughput sequencing showed that they have respectively carried a c.489delG (p.Q165Rfs*14) and a c.1157_1158delAT (p.Y386Cfs*22) frameshifting variant of the CTCF gene, both had a de novo origin and were unreported previously. CONCLUSION: The CTCF gene variants probably underlay the development delay in the two children. Above discovery has enriched the mutational spectrum of the CTCF gene and has important implications for revealing the genotype-phenotype correlation for similar patients.

Lien vers le texte intégral (Open Access ou abonnement)

20. Mendes SL, Pinaya WHL, Pan PM, Jackowski AP, Bressan RA, Sato JR. Generalizability of 3D CNN models for age estimation in diverse youth populations using structural MRI. Scientific reports. 2023; 13(1): 6886.

Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models’ performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value < 0.001) within and between datasets. In addition, most models showed a moderate to high correlation in age estimation. The results, including the models' brain regions of interest (ROI), were analyzed and discussed in light of the youth neurodevelopmental structural changes. Among other interesting discoveries, we found that less confounded training datasets produce models with higher generalization capacity.

Lien vers le texte intégral (Open Access ou abonnement)

21. Munz M, Bharioke A, Kosche G, Moreno-Juan V, Brignall A, Rodrigues TM, Graff-Meyer A, Ulmer T, Haeuselmann S, Pavlinic D, Ledergerber N, Gross-Scherf B, Rózsa B, Krol J, Picelli S, Cowan CS, Roska B. Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex. Cell. 2023; 186(9): 1930-49.e31.

Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that mouse embryonic Rbp4-Cre cortical neurons, transcriptomically closest to layer 5 pyramidal neurons, display two phases of circuit assembly in vivo. At E14.5, they form a multi-layered circuit motif, composed of only embryonic near-projecting-type neurons. By E17.5, this transitions to a second motif involving all three embryonic types, analogous to the three adult layer 5 types. In vivo patch clamp recordings and two-photon calcium imaging of embryonic Rbp4-Cre neurons reveal active somas and neurites, tetrodotoxin-sensitive voltage-gated conductances, and functional glutamatergic synapses, from E14.5 onwards. Embryonic Rbp4-Cre neurons strongly express autism-associated genes and perturbing these genes interferes with the switch between the two motifs. Hence, pyramidal neurons form active, transient, multi-layered pyramidal-to-pyramidal circuits at the inception of neocortex, and studying these circuits could yield insights into the etiology of autism.

Lien vers le texte intégral (Open Access ou abonnement)

22. Oberman LM, Leonard H, Downs J, Cianfaglione R, Stahlhut M, Larsen JL, Madden KV, Kaufmann WE. Rett Syndrome Behaviour Questionnaire in Children and Adults With Rett Syndrome: Psychometric Characterization and Revised Factor Structure. American journal on intellectual and developmental disabilities. 2023; 128(3): 237-53.

Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with multiple neurobehavioral abnormalities. The Rett Syndrome Behaviour Questionnaire (RSBQ) was developed for pediatric RTT observational studies. Because its application has expanded to adult and interventional studies, we evaluated the RSBQ’s psychometric properties in six pediatric (n = 323) and five adult (n = 309) datasets. Total and General Mood subscale scores had good reliability. Clinical severity had no influence on RSBQ scores. Exploratory and confirmatory factor analyses yielded 6 pediatric and 7 adult clinically relevant and psychometrically strong factors including the original Breathing Problems and Fear/Anxiety subscales and the novel Emotional and Disruptive Behavior subscale composed of items from the original General Mood and Nighttime Behaviours subscales. The present findings support additional evaluations and improvements of an important RTT behavioral measure.

Lien vers le texte intégral (Open Access ou abonnement)

23. Rimmer C, Dahary H, Quintin EM. Links between musical beat perception and phonological skills for autistic children. Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence. 2023: 1-20.

Exploring non-linguistic predictors of phonological awareness, such as musical beat perception, is valuable for children who present with language difficulties and diverse support needs. Studies on the musical abilities of children on the autism spectrum show that they have average or above-average musical production and auditory processing abilities. This study aimed to explore the relationship between musical beat perception and phonological awareness skills of children on the autism spectrum with a wide range of cognitive abilities. A total of 21 autistic children between the ages of 6 to 11 years old (M = 8.9, SD = 1.5) with full scale IQs ranging from 52 to 105 (M = 74, SD = 16) completed a beat perception and a phonological awareness task. Results revealed that phonological awareness and beat perception are positively correlated for children on the autism spectrum. Findings lend support to the potential use of beat and rhythm perception as a screening tool for early literacy skills, specifically for phonological awareness, for children with diverse support needs as an alternative to traditional verbal tasks that tend to underestimate the potential of children on the autism spectrum.

Lien vers le texte intégral (Open Access ou abonnement)

24. Saga T, Tanaka H, Matsuda Y, Morimoto T, Uratani M, Okazaki K, Fujimoto Y, Nakamura S. Automatic evaluation-feedback system for automated social skills training. Scientific reports. 2023; 13(1): 6856.

Social skills training (SST), which is a rehabilitation program for improving daily interpersonal communication, has been used for more than 40 years. Although such training’s demand is increasing, its accessibility is limited due to the lack of experienced trainers. To tackle this issue, automated SST systems have been studied for years. An evaluation-feedback pipeline of social skills is a crucial component of an SST system. Unfortunately, research that considers both the evaluation and feedback parts of automation remains insufficient. In this paper, we collected and analyzed the characteristics of a human-human SST dataset that consisted of 19 healthy controls, 15 schizophreniacs, 16 autism spectrum disorder (ASD) participants, and 276 sessions with score labels of six clinical measures. From our analysis of this dataset, we developed an automated SST evaluation-feedback system under the supervision of professional, experienced SST trainers. We identified their preferred or most acceptable feedback methods by running a user-study on the following conditions: with/without recorded video of the role-plays of users and different amounts of positive and corrective feedback. We confirmed a reasonable performance of our social-skill-score estimation models as our system’s evaluation part with a maximum Spearman’s correlation coefficient of 0.68. For the feedback part, our user-study concluded that people understood more about what aspects they need to improve by watching recorded videos of their own performance. In terms of the amount of feedback, participants most preferred a 2-positive/1-corrective format. Since the average amount of feedback preferred by the participants nearly equaled that from experienced trainers in human-human SSTs, our result suggests the practical future possibilities of an automated evaluation-feedback system that complements SSTs done by professional trainers.

Lien vers le texte intégral (Open Access ou abonnement)

25. Santos S, Martins B, Sereno J, Martins J, Castelo-Branco M, Gonçalves J. Neurobehavioral sex-related differences in Nf1(+/-) mice: female show a « camouflaging »-type behavior. Biology of sex differences. 2023; 14(1): 24.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). This condition has been associated with an increase of gamma-aminobutyric acid (GABA) neurotransmission and, consequently, an excitation/inhibition imbalance associated with autistic-like behavior in both human and animal models. Here, we explored the influence of biological sex in the GABAergic system and behavioral alterations induced by the Nf1(+/-) mutation in a murine model. METHODS: Juvenile male and female Nf1(+/-) mice and their wild-type (WT) littermates were used. Hippocampus size was assessed by conventional toluidine blue staining and structural magnetic resonance imaging (MRI). Hippocampal GABA and glutamate levels were determined by magnetic resonance spectroscopy (MRS), which was complemented by western blot for the GABA(A) receptor. Behavioral evaluation of on anxiety, memory, social communication, and repetitive behavior was performed. RESULTS: We found that juvenile female Nf1(+/-) mice exhibited increased hippocampal GABA levels. Moreover, mutant female displays a more prominent anxious-like behavior together with better memory performance and social behavior. On the other hand, juvenile Nf1(+/-) male mice showed increased hippocampal volume and thickness, with a decrease in GABA(A) receptor levels. We observed that mutant males had higher tendency for repetitive behavior. CONCLUSIONS: Our results suggested a sexually dimorphic impact of Nf1(+/-) mutation in hippocampal neurochemistry, and autistic-like behaviors. For the first time, we identified a « camouflaging »-type behavior in females of an animal model of ASD, which masked their autistic traits. Accordingly, like observed in human disorder, in this animal model of ASD, females show larger anxiety levels but better executive functions and production of normative social patterns, together with an imbalance of inhibition/excitation ratio. Contrary, males have more externalizing disorders, such as hyperactivity and repetitive behaviors, with memory deficits. The ability of females to camouflage their autistic traits creates a phenotypic evaluation challenge that mimics the diagnosis difficulty observed in humans. Thus, we propose the study of the Nf1(+/-) mouse model to better understand the sexual dimorphisms of ASD phenotypes and to create better diagnostic tools.

Lien vers le texte intégral (Open Access ou abonnement)

26. Schroeder K, Rosselló J, Torrades TR, Hinzen W. Linguistic markers of autism spectrum conditions in narratives: A comprehensive analysis. Autism & developmental language impairments. 2023; 8: 23969415231168557.

Background & Aims: Narratives are regularly elicited as part of standardized assessments for autism spectrum conditions (ASC) such as the ADOS, but have rarely been utilized as linguistic data in their own right. We here aimed for a specific and comprehensive quantitative linguistic profile of such narratives across nominal, verbal, and clausal domains of grammatical organization, and error patterns. Methods: We manually transcribed and annotated narratives elicited from the ADOS from a sample of bilingual autistic Spanish-Catalan children (n = 18), matched with typically developing controls (n = 18) on vocabulary-based verbal IQ. Results: Results revealed fewer relative clauses and more frequent errors in referential specificity and non-relational content-word choice in ASC. Frequent error types are also discussed qualitatively. Conclusions & Implications: These findings, based on more finegrained linguistically defined variables, help to disentangle previous inconsistencies in the literature, and to better situate language changes in the spectrum of neurocognitive changes in this population.

Lien vers le texte intégral (Open Access ou abonnement)

27. Tomas V, Hsu S, Kingsnorth S, Anagnostou E, Kirsh B, Lindsay S. Development and Usability Testing of a Web-Based Workplace Disability Disclosure Decision Aid Tool for Autistic Youth and Young Adults: Qualitative Co-design Study. JMIR formative research. 2023; 7: e44354.

BACKGROUND: Deciding whether and how to disclose one’s autism at work is complex, especially for autistic youth and young adults who are newly entering the labor market and still learning important decision-making and self-determination skills. Autistic youth and young adults may benefit from tools to support disclosure processes at work; however, to our knowledge, no evidence-based, theoretically grounded tool exists specifically for this population. There is also limited guidance on how to pursue the development of such a tool in collaboration with knowledge users. OBJECTIVE: This study aimed to co-design a prototype of a disclosure decision aid tool with and for Canadian autistic youth and young adults, explore the perceived usability of the prototype (usefulness, satisfaction, and ease of use) and make necessary revisions, and outline the process used to achieve the aforementioned objectives. METHODS: Taking a patient-oriented research approach, we engaged 4 autistic youths and young adults as collaborators on this project. Prototype development was guided by co-design principles and strategies, and tool content was informed by a previous needs assessment led by our team, the autistic collaborators’ lived experiences, considering intersectionality, research on knowledge translation (KT) tool development, and recommendations from the International Patient Decision Aid Standards. We co-designed a web-based PDF prototype. To assess perceived usability and experiences with the prototype, we conducted 4 participatory design and focus group Zoom (Zoom Video Communications) sessions with 19 Canadian autistic youths and young adults aged 16 to 29 (mean 22.8, SD 4.1) years. We analyzed the data using a combined conventional (inductive) and modified framework method (deductive) analysis to map the data onto usability indicators (usefulness, satisfaction, and ease of use). Grounded in participants’ feedback, considering factors of feasibility and availability of resources, and ensuring tool fidelity, we revised the prototype. RESULTS: We developed 4 categories pertaining to the perceived usability of and participant experiences with the prototype: past disclosure experiences, prototype information and activities, prototype design and structure, and overall usability. Participant feedback was favorable and indicative of the tool’s potential impact and usability. The usability indicator requiring the most attention was ease of use, which was prioritized when revising the prototype. Our findings highlight the importance of engaging knowledge users throughout the entire prototype co-design and testing processes; incorporating co-design strategies and principles; and having content informed by relevant theories, evidence, and knowledge users’ experiences. CONCLUSIONS: We outline an innovative co-design process that other researchers, clinicians, and KT practitioners may consider when developing KT tools. We also developed a novel, evidence-based, and theoretically informed web-based disclosure decision aid tool that may help autistic youth and young adults navigate disclosure processes and improve their transitional outcomes as they enter the workforce.

Lien vers le texte intégral (Open Access ou abonnement)

28. Wallace-Watkin C, Sigafoos J, Woods L, Waddington H. Parent reported barriers and facilitators to support services for autistic children in Aotearoa New Zealand. Autism : the international journal of research and practice. 2023: 13623613231168240.

Parents might have problems in getting support services for their autistic child due to certain barriers. However, there might also be things that can ease or facilitate parents’ access to support services. In this study, New Zealand parents were asked about their experiences in getting support services for their autistic child. We also looked at differences in reported barriers and facilitators based on several demographic factors with a focus on family level of financial resourcing. A total of 173 parents completed a survey. The results suggested that parents experienced several barriers, particularly related to service pathways. Facilitators were also experienced, predominantly related to providers. Financial resourcing predicted the number of parent-reported barriers. Both lower level of family financial resourcing and having a non-binary child predicted parents’ rating of the extent of barriers. Child age and level of speech were predictors for reports of experiencing a higher number of facilitators, with parents of younger children or of non-speaking autistic children reporting a greater number of facilitators. We discuss how these results may be useful to support service delivery and identify areas for future research.

Lien vers le texte intégral (Open Access ou abonnement)

29. Wang L, Li S, Wang C. Using Pivotal Response Treatment to Improve Language Functions of Autistic Children in Special Schools: A Randomized Controlled Trial. Journal of autism and developmental disorders. 2023: 1-13.

Language difficulties exert profound negative effects on the cognitive and social development of autistic children. Pivotal Response Treatment (PRT) is a promising intervention for improving social communication in autistic children, but there is a lack of a comprehensive examination of language functions. This study aimed to investigate the effectiveness of PRT in promoting the primary language functions (requesting, labeling, repeating, responding) defined by (Skinner, B. F. (1957). Verbal behavior. Martino Publishing.) theory of verbal behavior in autistic children. Thirty autistic children were randomly divided into the PRT group (M(age) = 6.20, SD(age) = 1.21) and control group (M(age) = 6.07, SD(age) = 1.49). The PRT group were provided with an 8-week training of the PRT motivation component in addition to treatment as usual (TAU) in their schools, whereas the control group only received TAU. Parents of the PRT group were also trained to practice the PRT motivation procedures at home. The PRT group demonstrated greater improvements in all four measured language functions compared to the control group. The improvement in language functions in the PRT group was generalized and maintained at the follow-up assessment. In addition, the PRT intervention enhanced untargeted social and communicative functioning, cognition, motor skills, imitation, and adaptive behaviors in the autistic children. In conclusion, language intervention using the motivation component of PRT is effective in promoting language functions as well as widespread untargeted cognitive and social functions in autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

30. Yu G, Xu M, Chen Y, Ke H. 25(OH)Vitamin D and autism spectrum disorder: genetic overlap and causality. Genes & nutrition. 2023; 18(1): 8.

OBJECTIVE: To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD). METHODS: Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits. A bidirectional Mendelian randomization (MR) analysis was applied to investigate whether there is a causal relationship between 25(OH)D and ASD. RESULTS: The linkage disequilibrium score regression (LDSC) showed a negative genetic correlation between 25(OH)D and ASD (r(g) = – 0.227, P < 0.05), and PLACO analysis identified 20 independent pleiotropic loci matched to 24 pleiotropic genes, of which the function reveals an underlying mechanism on 25(OH)D and ASD. In Mendelian randomization analysis, the inverse variance-weighted (IVW) method with OR = 0.941 (0.796, 1.112) and p < 0.474 did not show a causal relationship between 25(OH)D and ASD, while, in the reverse Mendelian randomization analysis, IVW method showed OR = 1.042 (0.930, 1.169), indicating no causal relationship either. CONCLUSION: This study provides evidence for a shared genetic overlap between 25(OH)D and ASD. Bidirectional MR analysis also did not show a definite causal relationship between 25(OH)D and ASD.

Lien vers le texte intégral (Open Access ou abonnement)