1. Aykut P, Kahveci G. The effect of conjoint behavioral consultation on achieving communication skills in children with autism spectrum disorder. Int J Dev Neurosci;2024 (Aug 12)

This study, uniquely designed with tact and mand-modeling procedures presented through the Conjoint Behavioral Consultation (CBC) method, aims to evaluate the effects on the communication skills of preschool children with autism spectrum disorder (ASD) and the impact on disruptive behaviors (tantrums) at home. A pilot study with the families of three participants informed the adaptations for the main study, which was implemented with the families of nine participants. The research was conducted using an Embedded Mixed Methods Design, a distinctive approach that allowed for a comprehensive understanding of the outcomes. The primary research design was a single-subject research model with multiple probes across participants’ designs, ensuring a thorough and individualized assessment. The study was carried out in both home and clinical settings, involving the participation of special education teachers and families. The findings indicate that the tact and mand-modeling procedures presented through the CBC method significantly improved the children’s communication skills and led to substantial reductions in tantrum behaviors. All families indicated that the dependent variables held significant social importance. Significant enhancements were noted in the children’s communication skills and social engagements after the intervention. The CBC intervention was determined to be feasible and feasible for families, with no additional expenses accrued. The long-term suitability and usefulness of the product in many environments increased its societal acceptance. This study revealed that the CBC approach had a favorable and reliable effect on academic and behavioral advancement.

Lien vers le texte intégral (Open Access ou abonnement)

2. Bang P, Andemichael DK, Pieslinger JF, Igelström K. Sensory symptoms associated with autistic traits and anxiety levels in children aged 6-11 years. J Neurodev Disord;2024 (Aug 12);16(1):45.

BACKGROUND: Autism spectrum conditions (ASC) and quantitative autistic traits (QATs) are associated with sensory symptoms, which may contribute to anxiety and adversely affect social and cognitive development. Although sensory symptoms can occur across all senses, the relative roles of specific sensory modalities as contributors to the autistic phenotype and to anxiety are not well understood. The objective of this study was to examine which sensory symptoms were most predictive of high anxiety. METHODS: We recruited 257 female primary caregivers of children aged 6 to 11 years (49% girls) to a questionnaire study comprising parent-report measures for classical QATs (social, communicative, and rigid), autism-related sensorimotor symptoms (visual, auditory, tactile, olfactory, gustatory, vestibular, proprioceptive, and motor), and anxiety symptoms. First, Bayesian stochastic search variable selection (SSVS) was used to identify the most probable sensorimotor predictors of specific QATs as well as diagnosed ASC. Then, the selected predictors were used in another SSVS, using anxiety symptoms as a dependent variable, to identify which of the autism-relevant sensorimotor symptoms were most robustly predictive of anxiety. Finally, the effect sizes of anxiety-related sensory symptoms were estimated with linear regressions. RESULTS: We found that auditory symptoms and motor difficulties were most predictive of ASC diagnosis. Developmental motor difficulties were also strongly related to all individual QATs, whereas auditory symptoms were more selectively predictive of rigid traits. Tactile symptoms robustly predicted social interaction QATs, and proprioceptive symptoms predicted communicative QATs. Anxiety outcomes were most strongly predicted by difficulties with auditory and olfactory processing. CONCLUSIONS: The results support the clinical importance of being alert to complaints about sounds and hearing in neurodevelopmental populations, and that auditory processing difficulties may be evaluated as an early marker of poor mental health in children with and without diagnosed autism. Olfactory processing differences appeared to be an anxiety marker less strongly associated with ASC or QATs, while motor difficulties were highly autism-relevant but not equally strongly associated with anxiety outcomes. We suggest that future studies may focus on the mechanisms and consequences of neurodevelopmental central auditory processing dysfunction and its potential relationship to anxiety disorders.

Lien vers le texte intégral (Open Access ou abonnement)

3. Bedford SA, Lai MC, Lombardo MV, Chakrabarti B, Ruigrok A, Suckling J, Anagnostou E, Lerch JP, Taylor M, Nicolson R, Stelios G, Crosbie J, Schachar R, Kelley E, Jones J, Arnold PD, Courchesne E, Pierce K, Eyler LT, Campbell K, Barnes CC, Seidlitz J, Alexander-Bloch AF, Bullmore ET, Baron-Cohen S, Bethlehem RAI. Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology. Biol Psychiatry;2024 (Aug 9)

BACKGROUND: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Population modelling, often referred to as normative modelling, provides a unified framework for studying age-specific and sex-specific divergences in brain development. METHODS: Here we used population modelling and a large, multi-site neuroimaging dataset (N = 4255 after quality control) to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of average brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). RESULTS: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume, that was localised to the superior temporal cortex, whereas individuals with ADHD showed more global increases in cortical thickness, but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. CONCLUSIONS: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

Lien vers le texte intégral (Open Access ou abonnement)

4. Capelli E, Riva V, D’Alfonso S, Panichi V, Riboldi EM, Borgatti R, Molteni M, Provenzi L. Exploring the impact of parents’ face-mask wearing on dyadic interactions in infants at higher likelihood for autism compared with general population. J Exp Child Psychol;2024 (Aug 12);247:106037.

Since the COVID-19 pandemic, both the public and researchers have raised questions regarding the potential impact of protective face-mask wearing on infants’ development. Nevertheless, limited research has tested infants’ response to protective face-mask wearing adults in real-life interactions and in neurodiverse populations. In addition, scarce attention was given to changes in interactive behavior of adults wearing a protective face-mask. The aims of the current study were (1) to examine differences in 12-month-old infants’ behavioral response to an interactive parent wearing a protective face-mask during face-to-face interaction, (2) to investigate potential differences in infants at higher likelihood for autism (HL-ASD) as compared with general population (GP) counterparts, and (3) to explore significant differences in parents’ behaviors while wearing or not wearing a protective face-mask. A total of 50 mother-infant dyads, consisting of 20 HL-ASD infants (siblings of individuals with autism) and 30 GP infants, participated in a 6-min face-to-face interaction. The interaction was videotaped through teleconferencing and comprised three 2-min episodes: (a) no mask, (b) mask, and (c) post-mask. Infants’ emotionality and gaze direction, as well as mothers’ vocal production and touching behaviors, were coded micro-analytically. Globally, GP infants exhibited more positive emotionality compared with their HL-ASD counterparts. Infants’ negative emotionality and gaze avoidance did not differ statistically across episodes. Both groups of infants displayed a significant increase in looking time toward the caregiver during the mask episode. No statistically significant differences emerged in mothers’ behaviors. These findings suggest that the use of protective face-masks might not negatively affect core dimensions of caregiver-infant interactions in GP and HL-ASD 12-month-old infants.

Lien vers le texte intégral (Open Access ou abonnement)

5. Choi YY, Lee KS, Park SG, Kim YS, Lee J, Sung HK, Kim MH. COVID-19 and Neurodevelopmental Delays in Early Childhood: A Longitudinal Analysis of Developmental Outcomes in Korean Children. J Korean Med Sci;2024 (Aug 12);39(31):e243.

This study employed a longitudinal analysis to evaluate the association between the coronavirus disease 2019 pandemic and neurodevelopment by analyzing over 1.8 million children from the Korean Developmental Screening Test for Infants and Children included in South Korea’s National Health Screening Program. We compared the developmental outcomes in five age groups-9-17 months, 18-29 months, 30-41 months, 42-53 months, and 54-65 months-between the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Significant increases in potential developmental delays were observed during the pandemic in communication, cognitive, social interaction, self-care, and fine motor skills across most age groups. All five age groups experienced notable disruptions in communication and fine motor skills. Children from socioeconomically disadvantaged backgrounds faced higher risks across all domains. These findings highlight the need for targeted interventions and continuous monitoring to support the developmental needs of children affected by pandemic-related disruptions.

Lien vers le texte intégral (Open Access ou abonnement)

6. Constable T, Pilling RF, Woodhouse JM. Testing the Hard to Test: A Pilot Study Examining the Role of Questionnaires in Eliciting Visual Behaviours in Children with Autistic Spectrum Disorder. J Autism Dev Disord;2024 (Aug 12)

PURPOSE: There is a higher prevalence of visual problems in children with Autistic Spectrum Disorder (ASD) compared with the neuro-typical population. Issues relating to visual perception can be evident as atypical visual behaviours (ViBes). The aim of the study was to compare findings of parents and eye health professionals using questionnaires to describe visual function in young children with ASD. MATERIALS AND METHODS: Parents/Caregivers of patients diagnosed with ASD attending routine hospital eye clinics were invited to participate. A questionnaire to draw out presence of ViBes was completed by the parent prior to attending clinic. The clinician independently completed the same questionnaire and undertook a clinical ocular assessment. RESULTS: 32 children were recruited (mean age 7 years, range 4-11). Most caregivers indicated they had noted at least one atypical ViBe (97%, median 5, range 0-8). Parental-reported ViBe8 scores were higher than clinician-reported scores (p = 0.04). The most commonly reported ViBes by both groups related to use of vision at the same time as other senses, and atypical fixation (e.g. looking away during speech or side viewing). There was weak correlation between visual acuity and parental ViBe8 score (rho = 0.364) and no correlation between refractive error and parental ViBe8 score (rho = 0.047). CONCLUSION: Clinicians were likely to under-report atypical visual function compared with parent. Refraction and visual acuity alone do not detect all visual problems in children with ASD. A Visual Behaviour (ViBe) questionnaire offers a structured approach and shared language to allow documentation of functional visual assessment for both parents, carers, and educational professionals. Use of the ViBe questionnaire may promote understanding between caregiver and professional and provide a baseline for visual behaviours.

Lien vers le texte intégral (Open Access ou abonnement)

7. Elgenidy A, Gad EF, Shabaan I, Abdelrhem H, Wassef PG, Elmozugi T, Abdelfattah M, Mousa H, Nasr M, Salah-Eldin M, Altaweel A, Hussein A, Bazzazeh M, Elganainy MA, Ali AM, Ezzat M, Elhoufey A, Alatram AA, Hammour A, Saad K. Examining the association between autism spectrum disorder and atopic eczema: meta-analysis of current evidence. Pediatr Res;2024 (Aug 11)

OBJECTIVES: This study aims to investigate the association between autism spectrum disorder (ASD) and atopic eczema (AE), shedding light on potential associations and underlying mechanisms. METHODS: A comprehensive review of literature was conducted to identify relevant studies published up to August 2023. Various electronic databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched using specific keywords related to ASD and AE. RESULTS: The meta-analysis covered a total of 30 studies. The first analysis included 23 studies with a combined total of 147430 eczema patients in the ASD group and 8895446 eczema patients in non-ASD group. We calculated the risk ratio of eczema in ASD and non-ASD groups, which revealed a significantly higher risk of eczema in patients with ASD (RR 1.34; 95% CI 1.03, 1.76). The second analysis included seven studies with a combined total of 3570449 ASD patients in the AE group and 3253973 in the non-Eczema group. The risk ratio of ASD in the Eczema and Non-Eczema groups showed a significantly increased risk of ASD in patients with eczema (RR 1.67; 95% CI 0.91, 3.06). CONCLUSION: This study underscores the possible link between ASD and atopic eczema, shedding light on their potential association. IMPACT: Our study conducted a meta-analysis on the association between autism spectrum disorder (ASD) and atopic eczema (AE), shedding light on potential associations and underlying mechanisms. The review we conducted covered a total of 30 studies. This study underscores the possible link between ASD and atopic eczema, shedding light on their potential association.

Lien vers le texte intégral (Open Access ou abonnement)

8. Fellowes S. A history of childhood schizophrenia and lessons for autism. Hist Philos Life Sci;2024 (Aug 12);46(3):29.

The diagnosis of childhood schizophrenia was widely employed in the U.S. from the 1930s to the late 1970s. In this paper I will provide a history of the diagnosis. Some of the earliest publications on childhood schizophrenia outlined the notion that childhood schizophrenia had different types. I will outline the development of these types, outlining differing symptoms and causes associated with various types. I outline how different types of childhood schizophrenia were demarcated from one another primarily on age of onset and the type of psychosis which was believed to be present. I will outline how various child psychiatrists viewed the types of childhood schizophrenia posited by other child psychiatrists. I will outline the process of abandoning childhood schizophrenia. I use my history to challenge what I believe are misconceptions about childhood schizophrenia. Also, I will use my history to draw lessons for thinking about modern notions of autism. It shows potential problems around formulating psychiatric diagnoses around causes and how compromises might be needed to prevent those problems. Additionally, childhood schizophrenia shows that psychiatrists could formulate subtypes that are not based upon functioning levels and that we can conceive of subtypes as dynamic whereby someone can change which subtype they exhibit over time.

Lien vers le texte intégral (Open Access ou abonnement)

9. Friedman L, Moser C, Thurman AJ, Taylor JL, Abbeduto L, Klusek J. Description and predictors of self-determination in males and females with fragile X syndrome on the verge of adulthood. J Intellect Disabil Res;2024 (Aug 12)

BACKGROUND: Self-determination refers to setting goals and making decisions regarding one’s own life with support from others as needed. Research on people with intellectual and developmental disabilities has established the importance of self-determination for quality of life outcomes, such as increased independence and life satisfaction. However, self-determination has not been characterised specifically in fragile X syndrome (FXS), the leading inherited cause of intellectual disability. Relative to youth with other forms of intellectual and developmental disabilities, youth with FXS may face exceptional barriers to the development of self-determined behaviour. In addition to intellectual disability, the FXS behavioural profile is characterised by high rates of autism and anxiety that may further limit opportunities for youth with FXS. The heritable nature of the condition can also yield a distinctive family environment, with siblings and parents also living with fragile X or its associated conditions. Considering these unique challenges, the present study examined self-determination in young adult males and females with FXS and explored whether factors such as language skills, adaptive behaviour and autism traits were associated with self-determination capacity and opportunities. METHODS: The present study included 9 females and 36 males with FXS between the ages of 17 and 25 years. Caregivers (mothers or fathers) completed the American Institute for Research Self-Determination Assessment, which is a questionnaire that yields three scores: self-determination capacity, opportunities for self-determination at home and opportunities for self-determination at school. RESULTS: Caregivers endorsed a wide range of self-determination capacity and opportunities, with ratings for opportunities at home and school exceeding ratings of capacity. Better adaptive behaviour skills were associated with more self-determination capacity, and the presence of more autism traits was associated with fewer opportunities at school. CONCLUSIONS: Results from this study contribute to our understanding of avenues to best support young adults with FXS as they transition to adulthood. Our findings also have implications for practice, such that interventions targeting adaptive behaviours and self-determination may be an effective approach for promoting autonomy and independence for young adults with FXS. Additionally, caregivers and educators should continue to provide opportunities to practise self-determination, regardless of their perception of capacity.

Lien vers le texte intégral (Open Access ou abonnement)

10. Gharavi M, Salem K, Adabdokht R, Ghasemi M. Effectiveness of two visual-pedagogical methods for toothbrushing skills in autistic children: A randomized clinical trial. Spec Care Dentist;2024 (Aug 12)

AIM: This study aimed to compare the effectiveness of two visual pedagogy methods, video modeling and educational posters, on improving tooth-brushing autonomy in 10-12-year-old children with mild autism. METHODS: Sixty-four autistic children were randomly assigned to either the video or poster groups using the Rand function in Excel. Toothbrushing skills were divided into five stages: preparation, buccal, occlusal, lingual surfaces, and the end. These five stages comprised a total of 20 steps, with each step scored from 1 (not done at all) to 5 (done independently). The final score was calculated by averaging the scores of the five stages. The FONES method of toothbrushing was used for training. Follow-up assessments were conducted after 1 and 3 months. The data were analyzed using SPSS V26, including t-tests, Mann-Whitney U tests, and repeated-measures ANOVA. RESULTS: After 3 months, there were significant improvements in autonomy scores for both groups, with the video group showing greater benefits (4.37 ± 0.43) compared to the poster group (4.11 ± 0.49) (p = .03), with an effect size of η(2) = .07. CONCLUSION: Both video and poster methods were effective in improving tooth-brushing skills, but video modeling was associated with a higher total autonomy score.

Lien vers le texte intégral (Open Access ou abonnement)

11. Kiing JS, Kang YQ, Mulay KV, Lim TS, Chong SC, Tan MY, Chan YH, Lim AS, Aishworiya R. Screen time and social-emotional skills in preschoolers with developmental, behavioural or emotional issues in Singapore. Ann Acad Med Singap;2024 (Jul 24);53(7):410-419.

INTRODUCTION: This study aimed to determine patterns of screen viewing time (SVT) in preschool children with developmental, behavioural or emotional (DBE) issues, and to identify its relationship with social-emotional development. METHOD: This cross-sectional study involved children aged 0-5 years who were referred to a developmental paediatric clinic for DBE issues. Parents completed a screen time questionnaire, and the Devereux Early Childhood Assessment-Clinical (DECA-C) question-naire which assessed the social-emotional competence of the children. Data were analysed using logistic regression, correlational analyses and tests of comparison. RESULTS: Among 225 children (mean age: 32.4 months), mean daily SVT was 138 minutes. More than half (51.1%) of the children had clinical features of language delay, while 26.6% had features suggestive of autism spectrum disorder. Screen time was first introduced at a mean age of 13.8 months, with 32.4% of children previously experiencing higher SVT. Compared to SVT introduction after 1 year of age, SVT in the first 12 months was primarily to facilitate feeding (P<0.05). Children with higher past SVT had poorer attention, more aggression, and increased behavioural concerns. Children with DBE issues have significantly more screen time than same-aged peers. CONCLUSION: Children with DBE issues are exposed to SVT at a very young age and have significantly more screen time than their peers. It is crucial to guide parents to reduce SVT in early childhood, particularly around mealtimes.

Lien vers le texte intégral (Open Access ou abonnement)

12. Liu M, Jiang X, Zeng X, Guo Y, Zhang T, Fan X, Xu J, Wu Z, Pan D. A protective mechanism of heat inactivation to enhance Levilactobacillus brevis PDD-2 against alcohol-induced chronic liver disease based on proteomic analysis. Food Funct;2024 (Aug 12);15(16):8356-8369.

A proteomics-based analysis of the effect of heat inactivation on the alleviation of alcoholic liver disease (ALD) using Levilactobacillus brevis PDD-2 is presented, aimed at exploring the potential and mechanisms of postbiotic elements prepared through heat inactivation in the treatment of ALD. It was found that L. brevis PDD-2 and its postbiotic (heat-inactivated L. brevis PDD-2) alleviate chronic ALD via the gut-liver axis. In particular, heat-inactivated L. brevis PDD-2 significantly increased the relative abundance of Erysipelotrichaceae and better facilitated the oxidative stress balance in the liver. The tandem mass tag (TMT)-based quantitative proteomics technique analyses revealed that heat-inactivated L. brevis PDD-2 was associated with up-regulated expression levels of proteins related to the redox system, cellular metabolism, amino acid and oligopeptide transport, and surface proteins with immunomodulatory capacity. These findings provide a theoretical basis for developing novel therapeutic strategies and lay a solid foundation for further revealing its exhaustive mechanisms.

Lien vers le texte intégral (Open Access ou abonnement)

13. Makale MT, Nybo C, Blum K, Dennen CA, Elman I, Murphy KT. Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism. J Pers Med;2024 (Aug 12);14(8)

Autism spectrum condition (ASC) is a neurodevelopmental condition that is only partly responsive to prevailing interventions. ASC manifests core challenges in social skills, communication, and sensory function and by repetitive stereotyped behaviors, along with imbalances in the brain’s excitatory (E) and inhibitory (I) signaling. Repetitive transcranial magnetic stimulation (rTMS) has shown promise in ASC and may be a useful addition to applied behavioral analysis (ABA), a gold-standard psychotherapeutic intervention. We report an open-label clinical pilot (initial) study in which ABA-treated ASC persons (n = 123) received our personalized rTMS protocol (PrTMS). PrTMS uses low TMS pulse intensities and continuously updates multiple cortical stimulation locales and stimulation frequencies based on the spectral EEG and psychometrics. No adverse effects developed, and 44% of subjects had ASC scale scores reduced to below diagnostic cutoffs. Importantly, in PrTMS responders, the spectral EEG regression flattened, implying a more balanced E/I ratio. Moreover, with older participants, alpha peak frequency increased, a positive correlate of non-verbal cognition. PrTMS may be an effective ASC intervention, offering improved cognitive function and overall symptomatology. This warrants further research into PrTMS mechanisms and specific types of subjects who may benefit, along with validation of the present results and exploration of broader clinical applicability.

Lien vers le texte intégral (Open Access ou abonnement)

14. Mediane DH, Basu S, Cahill EN, Anastasiades PG. Medial prefrontal cortex circuitry and social behaviour in autism. Neuropharmacology;2024 (Aug 14);260:110101.

Autism spectrum disorder (ASD) has proven to be highly enigmatic due to the diversity of its underlying genetic causes and the huge variability in symptom presentation. Uncovering common phenotypes across people with ASD and pre-clinical models allows us to better understand the influence on brain function of the many different genetic and cellular processes thought to contribute to ASD aetiology. One such feature of ASD is the convergent evidence implicating abnormal functioning of the medial prefrontal cortex (mPFC) across studies. The mPFC is a key part of the ‘social brain’ and may contribute to many of the changes in social behaviour observed in people with ASD. Here we review recent evidence for mPFC involvement in both ASD and social behaviours. We also highlight how pre-clinical mouse models can be used to uncover important cellular and circuit-level mechanisms that may underly atypical social behaviours in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

15. Prescott KE, Mathée-Scott J, Bolt D, Saffran J, Ellis Weismer S. The effect of volatility in linguistic input on prediction behavior in autistic toddlers. Autism Res;2024 (Aug 11)

Domain-general prediction differences have been posited as underlying many aspects of the cognitive-behavioral profile in autism. An interesting potential implication of such differences is hyperplasticity of learning-the idea that autistic individuals may privilege more recent input over the accumulation of prior learning. Because real world language input is highly variable, hyperplasticity could have serious ramifications for language learning. To investigate potential hyperplasticity during a language processing task, we administered an experimental anticipatory eye movement (AEM) task to 2- to 3-year-old autistic children and neurotypical (NT) peers. Autistic children’s change in anticipation from before to after a switch in contingencies did not significantly differ from NT counterparts, failing to support claims of hyperplasticity in the linguistic domain. Analysis of individual differences among autistic children revealed that cognitive ability was associated with prediction of the initial, stable contingencies, but neither age nor receptive language related to task performance. Results are discussed in terms of clinical implications and the broader context of research investigating prediction differences in autism.

Lien vers le texte intégral (Open Access ou abonnement)

16. Starr AL, Fraser HB. A general principle governing neuronal evolution reveals a human-accelerated neuron type potentially underlying the high prevalence of autism in humans. bioRxiv;2024 (Aug 3)

The remarkable ability of a single genome sequence to encode a diverse collection of distinct cell types, including the thousands of cell types found in the mammalian brain, is a key characteristic of multicellular life. While it has been observed that some cell types are far more evolutionarily conserved than others, the factors driving these differences in evolutionary rate remain unknown. Here, we hypothesized that highly abundant neuronal cell types may be under greater selective constraint than rarer neuronal types, leading to variation in their rates of evolution. To test this, we leveraged recently published cross-species single-nucleus RNA-sequencing datasets from three distinct regions of the mammalian neocortex. We found a strikingly consistent relationship where more abundant neuronal subtypes show greater gene expression conservation between species, which replicated across three independent datasets covering >10(6) neurons from six species. Based on this principle, we discovered that the most abundant type of neocortical neurons-layer 2/3 intratelencephalic excitatory neurons-has evolved exceptionally quickly in the human lineage compared to other apes. Surprisingly, this accelerated evolution was accompanied by the dramatic down-regulation of autism-associated genes, which was likely driven by polygenic positive selection specific to the human lineage. In sum, we introduce a general principle governing neuronal evolution and suggest that the exceptionally high prevalence of autism in humans may be a direct result of natural selection for lower expression of a suite of genes that conferred a fitness benefit to our ancestors while also rendering an abundant class of neurons more sensitive to perturbation.

Lien vers le texte intégral (Open Access ou abonnement)

17. Tang B, Zhao J, Zhang C, Qi P, Zheng S, Xu C, Chen M, Ye X. Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder. Dev Neurobiol;2024 (Aug 11)

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T(+) Itpr3(tf)/J (BTBR) mice, a well-established model for autism research. Our investigation unveiled a reduction in parvalbumin-positive (PV(+)) neurons within the AC of BTBR mice. Remarkably, in vivo magnetic resonance spectroscopy studies disclosed an elevation in glutamate (Glu) levels alongside a decrement in γ-aminobutyric acid (GABA) levels in this cortical region. Additionally, transcriptomic analysis of the mouse model facilitated the classification of several ASD-associated genes based on their cellular function and pathways. By comparing autism risk genes with RNA transcriptome sequencing data from the ASD mouse model, we identified the recurrent target gene Scn1a and performed validation. Intriguingly, we uncovered the specific expression of Scn1a in cortical inhibitory neurons. These findings hold significant value for understanding the underlying neural mechanisms of abnormal sensory perception in animal models of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

18. Teerikorpi N, Lasser MC, Wang S, Kostyanovskaya E, Bader E, Sun N, Dea J, Nowakowski TJ, Willsey AJ, Willsey HR. Ciliary biology intersects autism and congenital heart disease. bioRxiv;2024 (Jul 31)

Autism spectrum disorder (ASD) commonly co-occurs with congenital heart disease (CHD), but the molecular mechanisms underlying this comorbidity remain unknown. Given that children with CHD come to clinical attention by the newborn period, understanding which CHD variants carry ASD risk could provide an opportunity to identify and treat individuals at high risk for developing ASD far before the typical age of diagnosis. Therefore, it is critical to delineate the subset of CHD genes most likely to increase the risk of ASD. However, to date there is relatively limited overlap between high confidence ASD and CHD genes, suggesting that alternative strategies for prioritizing CHD genes are necessary. Recent studies have shown that ASD gene perturbations commonly dysregulate neural progenitor cell (NPC) biology. Thus, we hypothesized that CHD genes that disrupt neurogenesis are more likely to carry risk for ASD. Hence, we performed an in vitro pooled CRISPR interference (CRISPRi) screen to identify CHD genes that disrupt NPC biology similarly to ASD genes. Overall, we identified 45 CHD genes that strongly impact proliferation and/or survival of NPCs. Moreover, we observed that a cluster of physically interacting ASD and CHD genes are enriched for ciliary biology. Studying seven of these genes with evidence of shared risk (CEP290, CHD4, KMT2E, NSD1, OFD1, RFX3, TAOK1), we observe that perturbation significantly impacts primary cilia formation in vitro. While in vivo investigation of TAOK1 reveals a previously unappreciated role for the gene in motile cilia formation and heart development, supporting its prediction as a CHD risk gene. Together, our findings highlight a set of CHD risk genes that may carry risk for ASD and underscore the role of cilia in shared ASD and CHD biology.

Lien vers le texte intégral (Open Access ou abonnement)

19. Tepencelik ON, Wei W, Luo M, Cosman P, Dey S. Behavioral Intervention for Adults With Autism on Distribution of Attention in Triadic Conversations: A/B-Tested Pre-Post Study. JMIR Form Res;2024 (Aug 12);8:e55339.

BACKGROUND: Cross-neurotype differences in social communication patterns contribute to high unemployment rates among adults with autism. Adults with autism can be unsuccessful in job searches or terminated from employment due to mismatches between their social attention behaviors and society’s expectations on workplace communication. OBJECTIVE: We propose a behavioral intervention concerning distribution of attention in triadic (three-way) conversations. Specifically, the objective is to determine whether providing personalized feedback to each individual with autism based on an analysis of their attention distribution behavior during an initial conversation session would cause them to modify their orientation behavior in a subsequent conversation session. METHODS: Our system uses an unobtrusive head orientation estimation model to track the focus of attention of each individual. Head orientation sequences from a conversation session are analyzed based on five statistical domains (eg, maximum exclusion duration and average contact duration) representing different types of attention distribution behavior. An intervention is provided to a participant if they exceeded the nonautistic average for that behavior by at least 2 SDs. The intervention uses data analysis and video modeling along with a constructive discussion about the targeted behaviors. Twenty-four individuals with autism with no intellectual disabilities participated in the study. The participants were divided into test and control groups of 12 participants each. RESULTS: Based on their attention distribution behavior in the initial conversation session, 11 of the 12 participants in the test group received an intervention in at least one domain. Of the 11 participants who received the intervention, 10 showed improvement in at least one domain on which they received feedback. Independent t tests for larger test groups (df>15) confirmed that the group improvements are statistically significant compared with the corresponding controls (P<.05). Crawford-Howell t tests confirmed that 78% of the interventions resulted in significant improvements when compared individually against corresponding controls (P<.05). Additional t tests comparing the first conversation sessions of the test and control groups and comparing the first and second conversation sessions of the control group resulted in nonsignificant differences, pointing to the intervention being the main effect behind the behavioral changes displayed by the test group, as opposed to confounding effects or group differences. CONCLUSIONS: Our proposed behavioral intervention offers a useful framework for practicing social attention behavior in multiparty conversations that are common in social and professional settings.

Lien vers le texte intégral (Open Access ou abonnement)

20. Yang Y, Tang D, Wang Z, Liu Y, Chen F, Jie B, Ni T, Xu C, Li J, Wang C. Identification of high-functioning autism spectrum disorders based on gray-white matter functional network connectivity. J Psychiatr Res;2024 (Aug 6);178:107-113.

In the field of autism spectrum disorder (ASD), research on functional connectivity between gray matter and white matter remains under-researched. To address this gap, this study innovatively introduced a nested cross-validation method that integrates gray-white matter functional connectivity with an F-Score algorithm. This method calculates the correlation based on signals extracted from functional magnetic resonance imaging data using gray matter and white matter brain region templates. After applying the method to a New York University Langone Medical Center dataset consisting of 55 individuals with high-functioning ASD and 52 healthy subjects, we achieved a classification accuracy of 72.94%. This study found abnormal functional connectivity, primarily involving the left anterior prefrontal cortex and right superior corona radiata, left retrosplenial cortex and left superior corona radiata, as well as the left ventral anterior cingulate cortex and body of corpus callosum. Besides, we discovered that these abnormal connections are closely related to social impairment and restrictive and repetitive behaviors in ASD. In conclusion, this study provides a gray-white matter functional connectivity perspective for the diagnosis and understanding of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

21. Zhang X, Grove J, Gu Y, Buus CK, Nielsen LK, Neufeld SAS, Koko M, Malawsky DS, Wade E, Verhoef E, Gui A, Hegemann L, Geschwind DH, Wray NR, Havdahl A, Ronald A, St Pourcain B, Robinson EB, Bourgeron T, Baron-Cohen S, Børglum AD, Martin HC, Warrier V. An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles. medRxiv;2024 (Aug 2)

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h(2) (SNP) = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (r(g) = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

Lien vers le texte intégral (Open Access ou abonnement)