1. Carrier Screening Programs for Cystic Fibrosis, Fragile X Syndrome, Hemoglobinopathies and Thalassemia, and Spinal Muscular Atrophy: A Health Technology Assessment. Ont Health Technol Assess Ser;2023;23(4):1-398.

BACKGROUND: We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of carrier screening programs for cystic fibrosis (CF), fragile X syndrome (FXS), hemoglobinopathies and thalassemia, and spinal muscular atrophy (SMA) in people who are considering a pregnancy or who are pregnant. We also evaluated the budget impact of publicly funding carrier screening programs, and patient preferences and values. METHODS: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias tool and the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted cost-effectiveness analyses comparing preconception or prenatal carrier screening programs to no screening. We considered four carrier screening strategies: 1) universal screening with standard panels; 2) universal screening with a hypothetical expanded panel; 3) risk-based screening with standard panels; and 4) risk-based screening with a hypothetical expanded panel. We also estimated the 5-year budget impact of publicly funding preconception or prenatal carrier screening programs for the given conditions in Ontario. To contextualize the potential value of carrier screening, we spoke with 22 people who had sought out carrier screening. RESULTS: We included 107 studies in the clinical evidence review. Carrier screening for CF, hemoglobinopathies and thalassemia, FXS, and SMA likely results in the identification of couples with an increased chance of having an affected pregnancy (GRADE: Moderate). Screening likely impacts reproductive decision-making (GRADE: Moderate) and may result in lower anxiety among pregnant people, although the evidence is uncertain (GRADE: Very low).We included 21 studies in the economic evidence review, but none of the study findings were directly applicable to the Ontario context. Our cost-effectiveness analyses showed that in the short term, preconception or prenatal carrier screening programs identified more at-risk pregnancies (i.e., couples that tested positive) and provided more reproductive choice options compared with no screening, but were associated with higher costs. While all screening strategies had similar values for health outcomes, when comparing all strategies together, universal screening with standard panels was the most cost-effective strategy for both preconception and prenatal periods. The incremental cost-effectiveness ratios (ICERs) of universal screening with standard panels compared with no screening in the preconception period were $29,106 per additional at-risk pregnancy detected and $367,731 per affected birth averted; the corresponding ICERs in the prenatal period were about $29,759 per additional at-risk pregnancy detected and $431,807 per affected birth averted.We estimated that publicly funding a universal carrier screening program in the preconception period over the next 5 years would require between $208 million and $491 million. Publicly funding a risk-based screening program in the preconception period over the next 5 years would require between $1.3 million and $2.7 million. Publicly funding a universal carrier screening program in the prenatal period over the next 5 years would require between $128 million and $305 million. Publicly funding a risk-based screening program in the prenatal period over the next 5 years would require between $0.8 million and $1.7 million. Accounting for treatment costs of the screened health conditions resulted in a decrease in the budget impact of universally provided carrier screening programs or cost savings for risk-based programs.Participants value the perceived potential positive impact of carrier screening programs such as medical benefits from early detection and treatment, information for reproductive decision-making, and the social benefit of awareness and preparation. There was a strong preference expressed for thorough, timely, unbiased information to allow for informed reproductive decision-making. CONCLUSIONS: Carrier screening for CF, FXS, hemoglobinopathies and thalassemia, and SMA is effective at identifying at-risk couples, and test results may impact preconception and reproductive decision-making.The cost-effectiveness and budget impact of carrier screening programs are uncertain for Ontario. Over the short term, carrier screening programs are associated with higher costs, and also higher chances of detecting at-risk pregnancies compared with no screening. The 5-year budget impact of publicly funding universal carrier screening programs is larger than that of risk-based programs. However, accounting for treatment costs of the screened health conditions results in a decrease in the total additional costs for universal carrier screening programs or in cost savings for risk-based programs.The people we spoke with who had sought out carrier screening valued the potential medical benefits of early detection and treatment, particularly the support and preparation for having a child with a potential genetic condition.

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2. Alon-Tirosh M, Meir N. Use of social network sites among adolescents with autism spectrum disorder: a qualitative study. Front Psychol;2023;14:1192475.

BACKGROUND: Social network sites (SNS) have become an integral part of the daily lives of billions of users, including adolescents with autism spectrum disorder (ASD). There is a seeming contrast between ASD, characterized by social communication difficulties, and SNS use, requiring social skills. However, few studies examine these adolescents’ personal and subjective experiences on and their self-reports regarding the benefits and difficulties of using them. METHODS: This study examines the communication strategies of adolescents with ASD in using SNS, through semi-structured in-depth interviews with 10 adolescents diagnosed with ASD. RESULTS: Findings are on three main aspects: reasons for using SNS, actual SNS use, and social characteristics of ASD as expressed through SNS engagement. CONCLUSION: The main finding is that SNS use among adolescents with ASD exposes their deficiencies in communication despite providing emotional support. This study highlights the importance of guiding SNS use by adolescents with ASD.

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3. Angel L, Ailey SH, Delaney KR, Mohr L. Presentation of Depressive Symptoms in Autism Spectrum Disorders. West J Nurs Res;2023 (Sep);45(9):854-861.

BACKGROUND: Depressive disorders are frequently mis- and underdiagnosed in individuals with autism spectrum disorders (ASD). OBJECTIVE: Our objective was to identify and synthesize current knowledge regarding (1) the presentation of depressive symptoms and (2) the use of self-reports in assessing depressive symptoms in individuals with ASD and comparisons between self-reported and observer-reported symptoms. A scoping review was conducted to capture the full range of literature on the topic and to identify research gaps. METHODS: Articles were identified through a search of academic literature and screened for relevance to the aims of the review. RESULTS: In addition to typical depression symptoms, individuals with ASD may demonstrate atypical symptoms such as changes in autistic symptoms, self-injurious behavior, and psychomotor changes. Moreover, the review revealed a bias toward observer-reports of symptoms. Self-reports frequently were not included or were ascribed less weight than observer-reports. Self-reports typically differed from reports given by parents or other caregivers, but a consistent pattern in these differences has not been established. CONCLUSIONS: Further research on the use of self-reports in assessing depressive symptoms in individuals with ASD is needed. Self-reports may provide information not obtainable through observer-reports, and integrating both self- and observer-reports in psychiatric evaluations may produce more comprehensive and accurate assessments.

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4. Anning KL, Langley K, Hobson C, Van Goozen SHM. Dimensional associations between executive function processes and symptoms of ADHD, ASD, oppositional defiance and anxiety in young school-referred children. Cortex;2023 (Jul 10);167:132-147.

Executive function (EF) difficulties are implicated in Neurodevelopmental Disorders (NDDs), such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). Because NDDs are highly comorbid and frequently co-occur with additional clinical problems, it is unclear how specific EF problems are associated with symptoms of ASD and ADHD, whilst accounting for co-occurring anxiety or oppositional defiance disorder (ODD) symptoms. The current study utilised a large sample of young children (n = 438, aged 4-8) referred to Cardiff University’s Neurodevelopment Assessment Unit (NDAU) by teachers for cognitive and/or socio-emotional problems. As part of the referral process, the teachers completed the Strengths and Difficulties Questionnaire (SDQ), which revealed that most children displayed moderate to high hyperactivity (86%) and prosocial (73%) problems, as well as high levels of symptoms in other clinical domains (41% emotional, 61% conduct and 68% peer problems). Children completed tasks to assess episodic memory, cognitive inhibition, cognitive flexibility and visuomotor control, whilst parents completed questionnaires to measure symptoms of ASD, ADHD, anxiety and ODD. Dimensional analyses showed that poorer cognitive inhibition and visuospatial episodic memory were significantly associated with ADHD symptoms, whereas cognitive flexibility was negatively associated with ODD symptoms. Having more ASD symptoms was associated with fewer cognitive inhibition problems, whereas anxiety was associated with better cognitive flexibility. Our approach to assessment and analysis shows that specific cognitive processes are associated with distinct neurodevelopmental and clinical symptoms, which is ultimately relevant to early identification of and intervention for young children at risk of cognitive and/or socio-emotional problems.

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5. Baker A, Tomchek SD, Little LM, Wallisch A, Dean E. Interventions to Support Participation in Basic and Instrumental Activities of Daily Living for Autistic Children and Adolescents (2013-2021). Am J Occup Ther;2023 (Mar 1);77(Suppl 1)

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association’s Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from the systematic review on interventions to support participation in basic and instrumental activities of daily living by autistic1 children and adolescents (birth to 18 yr).

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6. Barbaro J, Winata T, Gilbert M, Nair R, Khan F, Lucien A, Islam R, Masi A, Diaz AM, Dissanayake C, Karlov L, Descallar J, Eastwood J, Hasan I, Jalaludin B, Kohlhoff J, Liaw ST, Lingam R, Ong N, Tam CWM, Woolfenden S, Eapen V. General practitioners’ perspectives regarding early developmental surveillance for autism within the australian primary healthcare setting: a qualitative study. BMC Prim Care;2023 (Aug 10);24(1):159.

BACKGROUND: Significant challenges remain in the early identification of child developmental disabilities in the community. Implementing supports and services early in the life course has been shown to promote positive developmental outcomes for children at high likelihood of developmental disabilities, including autism. As part of a cluster randomised controlled trial, this study seeks to examine and compare the perspectives and experiences of Australian general practitioners (GPs) in relation to a digital developmental surveillance program for autism and usual care pathway, in general practice clinics. METHODS: A qualitative research methodology with semi-structured interviews and thematic inductive analysis underpinned by grounded theory was utilised. All GPs from South Western Sydney (NSW) and Melbourne (Victoria) who participated in the main program (« GP Surveillance for Autism ») were invited to the interview. GPs who provided consent were interviewed either over online or in-person meeting. Interviews were audio-recorded, transcribed, and coded using NVivo12 software. Inductive interpretive approach was adopted and data were analysed thematically. RESULTS: Twenty-three GPs across the two sites (NSW: n = 11; Victoria: n = 12) agreed to be interviewed; data saturation had reached following this number of participants. Inductive thematic coding and analysis yielded eight major themes and highlighted common enablers such as the role of GPs in early identification and subsequent supports, enhanced communication between clinicians/professionals, relationship-building with patients, and having standardised screening tools. Specific facilitators to the feasibility and acceptability of a digital screening program for the early identification of developmental disabilities, including the early signs of autism, and encouraging research and education for GPs. However, several practical and socioeconomic barriers were identified, in addition to limited knowledge and uptake of child developmental screening tools as well as COVID-19 lockdown impacts. Common and specific recommendations involve supporting GPs in developmental/paediatrics training, streamlined screening process, and funding and resources in the primary healthcare services. CONCLUSIONS: The study highlighted the need for practice and policy changes, including further training of GPs alongside sufficient time to complete developmental checks and appropriate financial remuneration through a Medicare billing item. Further research is needed on implementation and scale up of a national surveillance program for early identification of developmental disabilities, including autism.

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7. Church MJ, Mangen KH, Stiede JT, Spencer SD, Storch EA. The role of between-session homework in cognitive-behavioral therapy for comorbid obsessive-compulsive disorder and autism: A case vignette. J Clin Psychol;2023 (Aug 10)

OBJECTIVE: Cognitive-behavioral therapy (CBT), which includes a decided emphasis on exposure and response/ritual prevention (ERP) and between-session practice of treatment principles, has consistently demonstrated efficacy for the treatment of obsessive-compulsive disorder (OCD) and is a gold standard, recommended first-line treatment. CBT with ERP has been successfully adapted to fit the needs of autistic individuals with OCD. The present article provides a brief overview of CBT for OCD and outlines special considerations and adaptations needed when working with patients with OCD and comorbid autism, with an emphasis on the importance of between-session homework. METHOD: A case vignette is presented. RESULTS: This case study illustrates the role of homework in the exposure-based treatment of an adult autistic individual with comorbid OCD. CONCLUSION: Implications of this case vignette are discussed, and recommendations are offered for clinicians working with autistic individuals with OCD, especially in regard to bolstering completion of between-session ERP homework.

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8. Gao N, Liu Z, Wang H, Shen C, Dong Z, Cui W, Xiong WC, Mei L. Deficiency of Cullin 3, a protein encoded by a schizophrenia and autism risk gene, impairs behaviors by enhancing the excitability of ventral tegmental area (VTA) DA neurons. J Neurosci;2023 (Aug 8)

The dopaminergic neuromodulator system is fundamental to brain functions. Abnormal dopamine (DA) pathway is implicated in psychiatric disorders including schizophrenia (SZ) and autism spectrum disorder (ASD). Mutations in Cullin 3 (CUL3), a core component of the Cullin-RING ubiquitin E3 ligase complex, have been associated with SZ and ASD. However, little is known about the function and mechanism of CUL3 in the DA system. Here, we show that CUL3 is critical for the function of DA neurons and DA-relevant behaviors in male mice. CUL3-deficient mice exhibited hyperactive locomotion, deficits in working memory and sensorimotor gating, and increased sensitivity to psychostimulants. In addition, enhanced DA signaling and elevated excitability of the ventral tegmental area (VTA) DA neurons were observed in CUL3-deficient animals. Behavioral impairments were attenuated by dopamine D2 receptor antagonist haloperidol and chemogenetic inhibition of DA neurons. Furthermore, we identified HCN2, a hyperpolarization-activated and cyclic nucleotide-gated channel, as a potential target of CUL3 in DA neurons. Our study indicates that CUL3 controls DA neuronal activity by maintaining ion channel homeostasis and provides insight into the role of CUL3 in the pathogenesis of psychiatric disorders.Significance StatementThis study provides evidence that Cullin 3, a core component of the Cullin-RING ubiquitin E3 ligase complex that has been associated with ASD and SZ, controls the excitability of DA neurons in mice. Its DA-specific heterozygous deficiency increased spontaneous locomotion, impaired working memory and sensorimotor gating, and elevated response to psychostimulants. We showed that CUL3 deficiency increased the excitability of VTA DA neurons, and inhibiting D2 receptor or DA neuronal activity attenuated behavioral deficits of CUL3-deficient mice. We found HCN2, a hyperpolarization-activated channel, as a target of CUL3 in DA neurons. Our findings reveal CUL3’s role in DA neurons and offer insights into the pathogenic mechanisms of ASD and SZ.

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9. Hawthorne K, Loveall SJ. The Effects of Syntactic, Semantic, and Pragmatic Prominence on Pronoun Interpretation in Adults With Intellectual and Developmental Disabilities. J Speech Lang Hear Res;2023 (Aug 10):1-16.

PURPOSE: Pronouns are referentially ambiguous: For example, « she » could refer to any female. Nonetheless, errors in pronoun interpretation rarely occur for adults with typical development (TD) due to several strategies implicitly shared between the talker and listener. The purpose of this study was to test the impacts of syntactic, semantic, and prosodic prominence on pronoun interpretation for adults with intellectual and developmental disabilities (IDD) and TD. METHOD: Adults with IDD (n = 28) and TD (n = 27) listened to ministories involving a pronoun with two potential antecedents that varied in syntactic, semantic, and pragmatic prominence. Subject/first-mentioned antecedents are more syntactically prominent than object antecedents. Semantic prominence was manipulated via verb transitivity: Subjects are more semantically prominent when the verb is highly transitive (e.g., « hit » vs. « see, » a low-transitivity verb for which the subject is merely experiencing the action). Pragmatic prominence was manipulated by placing prosodic focus on one of the two potential antecedents. Eye gaze to images representing the potential antecedents was tracked as a measure of online processing. Responses to a follow-up pronoun interpretation question were also recorded. RESULTS: Adults with TD used syntactic, semantic, and-in early processing-pragmatic prominence when interpreting ambiguous pronouns. Adults with IDD were sensitive to syntactic prominence but to a significantly lesser extent than their peers with TD. CONCLUSIONS: Pronouns are an integral part of everyday conversation, and when the conversational partners do not share common strategies to link ambiguous pronouns with their antecedents, misunderstandings will occur. Results show that adults with IDD only weakly share pronoun interpretation strategies with adults with TD, suggesting that pronouns may be an important focus for intervention for this population. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23875809.

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10. Jirikowic T, Ideishi R, Bendixen R, Pfeiffer B, Smythe R, Benevides T. Interventions for Social Participation for Autistic Adults (2013-2020). Am J Occup Ther;2023 (Mar 1);77(Suppl 1)

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association’s Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings on social participation interventions and participation outcomes for autistic1 adults.

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11. Jourdon A, Wu F, Mariani J, Capauto D, Norton S, Tomasini L, Amiri A, Suvakov M, Schreiner JD, Jang Y, Panda A, Nguyen CK, Cummings EM, Han G, Powell K, Szekely A, McPartland JC, Pelphrey K, Chawarska K, Ventola P, Abyzov A, Vaccarino FM. Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nat Neurosci;2023 (Aug 10)

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.

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12. Le Roy Olivos C, Núñez Farías A, López Espejo M, Coelho Medeiros E, Gálvez Fuenzalida A, Fuentes López E, Riquelme Pérez A. Impact of the COVID-19 pandemic on the eating behaviors of children and adolescents with autism spectrum disorder. Arch Argent Pediatr;2023 (Aug 10):e202202982.

Introduction. Children with autism spectrum disorder (ASD) have difficulties adapting to stressful situations, such as the COVID-19 pandemic. Objective. To assess the impact of the first year of the pandemic on feeding difficulties in children with ASD. Population and methods. The caregivers of children and adolescents with non-syndromic ASD (age: 2-18 years) from a neurodevelopment unit were invited to participate. Participants completed a questionnaire and the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) online before and during the first year of the pandemic. A priority score (product between the average frequency and the problem) for each BPFAS item was estimated. Results. Among the caregivers, 56.6% (86/152) completed the survey (mother: 74.4%); children’s median age was 6.3 years (p25-p75: 4.7-8.2); 80.2% of children were males; 58.1% continued with their therapy during the pandemic; and 61.6% had behavioral problems before the pandemic. During the first year of the pandemic, children had greater behavioral problems (34.9%) and feeding difficulties (61.6%); however, 31.4% of caregivers referred improvements in feeding. There were no significant differences in the BPFAS scores before and during the pandemic. The following items obtained the highest priority scores: gets up from table during meal, does not try new food, does not eat vegetables, does not eat fruits. Conclusions. A high frequency of feeding difficulties was noted during the first year of the pandemic. No differences were observed in feeding characteristics before and during the pandemic.

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13. Li C, Li T, Chen Y, Zhang C, Ning M, Qin R, Li L, Wang X, Chen L. Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity. Autism Res;2023 (Aug 10)

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.

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14. Lin F, Huang W, Lu S, Li J. Cerebral blood flow measured by diffuse correlation spectroscopy in children with autism spectrum disorder. J Biophotonics;2023 (Aug 10):e202300151.

Diffuse correlation spectroscopy (DCS) was used to measure resting-state cerebral blood flow (CBF) in temporal lobes of children with autism spectrum disorder (ASD) and typically developing (TD) children. Twenty-two children with ASD and 34 age-matched TD children were recruited to participate in the experiment. DCS signals were recorded with 3 long source-detector (SD) channels (SD distance = 22.0 mm) and 1 short SD channel (SD distance = 10.5 mm) from each side of the temporal lobe. Significant difference in CBF between left and right hemispheres was observed in ASD group, but not in TD group. With the degree of CBF lateralization as a discrimination feature, a leave-one-out ROC curve was plotted with the area-under-curve (AUC) value of 0.731 ± 0.010, indicating children with ASD could be discriminated from TD children. This suggested CBF lateralization in temporal lobes measured with DCS might serve as a discriminative feature for ASD.

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15. Marquis SN, McGrail KM, Lunsky Y, Baumbusch J. The Use of Medically Required Dental Services by Youth with Intellectual/Developmental Disabilities in British Columbia, Canada. J Can Dent Assoc;2023 (Jul);89:n7.

INTRODUCTION: The literature indicates that youth with intellectual/developmental disabilities (IDD), such as Down syndrome or autism, have poor oral health. A number of factors influence their oral health, including the use of medically required dental treatments. METHODS: This paper describes the first use of population-level administrative health data to examine the use of medically required dental services by youth with IDD compared with youth without IDD in Canada. RESULTS: Youth with IDD had 4-9 times the odds of a medically required dental treatment compared with youth without IDD. Odds varied with age and type of IDD. CONCLUSIONS: Youth with IDD used medically required dental services to a greater extent than youth without IDD. Use of medically required dental treatments by youth with IDD declined with age; this may indicate greater difficulty accessing services when youth transition from pediatric to adult services. These findings provide baseline information on the use of medically required dental treatments and can contribute to future assessments of dental services for youth with IDD.

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16. Molinaro G, Bowles JE, Croom K, Gonzalez D, Mirjafary S, Birnbaum S, Razak KA, Gibson JR, Huber KM. Female specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and Estrogen Receptor α. bioRxiv;2023 (Aug 10)

Autism manifests differently in males and females and the brain mechanisms that mediate these sex-dependent differences are unknown. Here, we demonstrate that deletion of the ASD-risk gene, Pten, in neocortical pyramidal neurons ( (NSE) Pten KO) results in robust hyperexcitability of local neocortical circuits in female, but not male, mice, observed as prolonged, spontaneous persistent activity states (UP states). Circuit hyperexcitability in females is mediated by enhanced signaling of metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) to ERK and de novo protein synthesis. In support of this idea, Pten deleted cortical neurons have a female-specific increase in mGluR5 levels and mGluR5-driven protein synthesis rates, mGluR5-ERα complexes are elevated in female cortex and genetic reduction of ERα in Pten KO cortical neurons rescues circuit excitability, protein synthesis rates and enhanced neuron size selectively in females. Abnormal timing and hyperexcitability of neocortical circuits in female (NSE) Pten KO mice are associated with deficits in temporal processing of sensory stimuli and social behaviors as well as mGluR5-dependent seizures. Female-specific cortical hyperexcitability and mGluR5-dependent seizures are also observed in a human disease relevant mouse model, germline Pten +/-mice. Our results reveal molecular mechanisms by which sex and a high impact ASD-risk gene interact to affect brain function and behavior.

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17. Perna J, Bellato A, Ganapathy PS, Solmi M, Zampieri A, Faraone SV, Cortese S. Correction: Association between autism spectrum disorder (ASD) and vision problems. A systematic review and meta-analysis. Mol Psychiatry;2023 (Aug 9)

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18. Pomè A, Tyralla S, Zimmermann E. Altered oculomotor flexibility is linked to high autistic traits. Sci Rep;2023 (Aug 10);13(1):13032.

Autism is a multifaced disorder comprising sensory abnormalities and a general inflexibility in the motor domain. The sensorimotor system is continuously challenged to answer whether motion-contingent errors result from own movements or whether they are due to external motion. Disturbances in this decision could lead to the perception of motion when there is none and to an inflexibility with regard to motor learning. Here, we test the hypothesis that altered processing of gaze-contingent sensations are responsible for both the motor inflexibility and the sensory overload in autism. We measured motor flexibility by testing how strong participants adapted in a classical saccade adaptation task. We asked healthy participants, scored for autistic traits, to make saccades to a target that was displaced either in inward or in outward direction during saccade execution. The amount of saccade adaptation, that requires to shift the internal target representation, varied with the autistic symptom severity. The higher participants scored for autistic traits, the less they adapted. In order to test for visual stability, we asked participants to localize the position of the saccade target after they completed their saccade. We found the often-reported saccade-induced mis-localization in low Autistic Quotient (AQ) participants. However, we also found mislocalization in high AQ participants despite the absence of saccade adaptation. Our data suggest that high autistic traits are associated with an oculomotor inflexibility that might produce altered processing of trans-saccadic vision which might increase the perceptual overstimulation that is experienced in autism spectrum disorders (ASD).

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19. Qin T, Wang Z, Li X, Zhang S. Selective Attentional Networks Deficits in Parents of Children With Autism Spectrum Disorder: Evidence From Attention Network Test. Psychiatry Investig;2023 (Aug);20(8):721-729.

OBJECTIVE: We primarily aimed to investigate the attention network function among parents of children with autism spectrum disorder (ASD) using the Attention Network Test (ANT). The secondary objective was to observe whether the three attention networks of all participants were related to each other. METHODS: We included 28 parents of children with ASD and 28 well-matched parents of typically developing children. All participants underwent the neuropsychological assessment and ANT test. The three distinct attention networks, including alerting, orienting, and executive control, were also measured. RESULTS: Compared with controls, parents of children with ASD showed less-efficient alerting and executive control network (all p<0.05), but not orienting network (p=0.74). No significant correlation was found between the alerting, orienting, and executive control network for either group. CONCLUSION: Our findings showed that parents of children with ASD had deficits in alerting and executive control attention functions. The deficits are indications of a broad autism phenotype.

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20. Ratcliff K, Hilton CL, Fingerhut PE, Jin Y, Hong I. Relationship between Emotional Support for Parents and Autistic Children’s Participation in Social and Physical Activities. Occup Ther Health Care;2023 (Aug 10):1-15.

The purpose of this study was to determine if parents receiving emotional support is positively correlated with children’s participation in physical and social activities and if such a correlation exists between parental emotional support in children labeled as autistic. Data were drawn from 30,501 children aged 6 to 17 years in the 2020 National Survey of Children’s Health database and analyzed using a retrospective cross-sectional approach based on multivariate linear regression models. Results showed parental emotional support was statistically significantly correlated with children’s physical and social activity in the total sample but was not significant for the emotional support of parents with autistic children. The findings suggest that other issues must be considered as contributing factors for parents of autistic children in relation to social and physical activity participation.

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21. Sysoeva O, Maximenko V, Kuc A, Voinova V, Martynova O, Hramov A. Abnormal spectral and scale-free properties of resting-state EEG in girls with Rett syndrome. Sci Rep;2023 (Aug 9);13(1):12932.

Spontaneous EEG contains important information about neuronal network properties that is valuable for understanding different neurological and psychiatric conditions. Rett syndrome (RTT) is a rare neurodevelopmental disorder, caused by mutation in the MECP2 gene. RTT is characterized by severe motor impairments that prevent adequate assessment of cognitive functions. Here we probe EEG parameters obtained in no visual input condition from a 28-channels system in 23 patients with Rett Syndrome and 38 their typically developing peers aged 3-17 years old. Confirming previous results, RTT showed a fronto-central theta power (4-6.25 Hz) increase that correlates with a progression of the disease. Alpha power (6.75-11.75 Hz) across multiple regions was, on the contrary, decreased in RTT, also corresponding to general background slowing reported previously. Among novel results we found an increase in gamma power (31-39.5 Hz) across frontal, central and temporal electrodes, suggesting elevated excitation/inhibition ratio. Long-range temporal correlation measured by detrended fluctuation analysis within 6-13 Hz was also increased, pointing to a more predictable oscillation pattern in RTT. Overall measured EEG parameters allow to differentiate groups with high accuracy, ROC AUC value of 0.92 ± 0.08, indicating clinical relevance.

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22. Taipale J. Caught on the surface: Tustin on autistic experience. Front Psychol;2023;14:1243310.

According to Frances Tustin, the core of autism is found in sensory modifications-and tactile modifications in particular. Tustin argues that sensory experiences may become self-absorbed to such an extent that the sensory environment experientially flattens into a two-dimensional « feel, » which complicates the individual’s relations with the external environment and other people. Focusing on these fundamental modifications and their experiential consequences, the article introduces Tustin’s main insight in terms of collapse of intentional depth, suggesting that this collapse concerns not only concrete spatial depth, but symbolic and intersubjective depth as well. By so doing, the article illustrates how Tustin’s ideas render intelligible certain commonly recognized features of autism, such as « deficits in the ability to initiate and to sustain reciprocal social interaction and social communication » and « restricted, repetitive, and inflexible patterns of behavior, interests or activities » (ICD-11).

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23. Washington P, Wall DP. A Review of and Roadmap for Data Science and Machine Learning for the Neuropsychiatric Phenotype of Autism. Annu Rev Biomed Data Sci;2023 (Aug 10);6:211-228.

Autism spectrum disorder (autism) is a neurodevelopmental delay that affects at least 1 in 44 children. Like many neurological disorder phenotypes, the diagnostic features are observable, can be tracked over time, and can be managed or even eliminated through proper therapy and treatments. However, there are major bottlenecks in the diagnostic, therapeutic, and longitudinal tracking pipelines for autism and related neurodevelopmental delays, creating an opportunity for novel data science solutions to augment and transform existing workflows and provide increased access to services for affected families. Several efforts previously conducted by a multitude of research labs have spawned great progress toward improved digital diagnostics and digital therapies for children with autism. We review the literature on digital health methods for autism behavior quantification and beneficial therapies using data science. We describe both case-control studies and classification systems for digital phenotyping. We then discuss digital diagnostics and therapeutics that integrate machine learning models of autism-related behaviors, including the factors that must be addressed for translational use. Finally, we describe ongoing challenges and potential opportunities for the field of autism data science. Given the heterogeneous nature of autism and the complexities of the relevant behaviors, this review contains insights that are relevant to neurological behavior analysis and digital psychiatry more broadly.

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