1. Cashin A, Kersten M, Howie V, Pracilio A, Morphet J, Griffin K, Trollor JN, Wilson NJ. The Experience of Facilitating Inclusive Research Advisory Groups With Parents and People With Intellectual Disability and/or Autism Spectrum Disorder. ANS Advances in nursing science. 2023.

There is little nursing research about process issues in conducting inclusive project advisory groups of people with autism and/or intellectual disability or those who are parents/carers of this cohort. Through a descriptive qualitative design, this article aims to analyze the processes, challenges, and solutions when facilitating these groups for a nursing project in Australia. Reflexive thematic analysis was utilized to analyze field notes and meeting minutes. Results highlight the need for a defined, robust communication process between researchers and advisory groups, skilled facilitators, and careful planning of when in the life of the project the groups can contribute meaningfully. This project offers a proposed framework for the valuable contribution of lived experiences from research advisory groups.

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2. Chen J, Engelhard M, Henao R, Berchuck S, Eichner B, Perrin EM, Sapiro G, Dawson G. Enhancing early autism prediction based on electronic records using clinical narratives. Journal of biomedical informatics. 2023: 104390.

Recent work has shown that predictive models can be applied to structured electronic health record (EHR) data to stratify autism likelihood from an early age (<1 year). Integrating clinical narratives (or notes) with structured data has been shown to improve prediction performance in other clinical applications, but the added predictive value of this information in early autism prediction has not yet been explored. In this study, we aimed to enhance the performance of early autism prediction by using both structured EHR data and clinical narratives. We built models based on structured data and clinical narratives separately, and then an ensemble model that integrated both sources of data. We assessed the predictive value of these models from Duke University Health System over a 14-year span to evaluate ensemble models predicting later autism diagnosis (by age 4 years) from data collected from ages 30 to 360 days. Our sample included 11,750 children above by age 3 years (385 meeting autism diagnostic criteria). The ensemble model for autism prediction showed superior performance and at age 30 days achieved 46.8% sensitivity (95% confidence interval, CI: 22.0%, 52.9%), 28.0% positive predictive value (PPV) at high (90%) specificity (CI: 2.0%, 33.1%), and AUC(4) (with at least 4-year follow-up for controls) reaching 0.769 (CI: 0.715, 0.811). Prediction by 360 days achieved 44.5% sensitivity (CI: 23.6%, 62.9%), and 13.7% PPV at high (90%) specificity (CI: 9.6%, 18.9%), and AUC(4) reaching 0.797 (CI: 0.746, 0.840). Results show that incorporating clinical narratives in early autism prediction achieved promising accuracy by age 30 days, outperforming models based on structured data only. Furthermore, findings suggest that additional features learned from clinician narratives might be hypothesis generating for understanding early development in autism.

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3. Corona LL, Wagner L, Hooper M, Weitlauf A, Foster TE, Hine J, Miceli A, Nicholson A, Stone C, Vehorn A, Warren Z. A Randomized Trial of the Accuracy of Novel Telehealth Instruments for the Assessment of Autism in Toddlers. Journal of autism and developmental disorders. 2023: 1-12.

PURPOSE: Telemedicine approaches to autism (ASD) assessment have become increasingly common, yet few validated tools exist for this purpose. This study presents results from a clinical trial investigating two approaches to tele-assessment for ASD in toddlers. METHODS: 144 children (29% female) between 17 and 36 months of age (mean = 2.5 years, SD = 0.33 years) completed tele-assessment using either the TELE-ASD-PEDS (TAP) or an experimental remote administration of the Screening Tool for Autism in Toddlers (STAT). All children then completed traditional in-person assessment with a blinded clinician, using the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3), and Autism Diagnostic Observation Schedule (ADOS-2). Both tele-assessment and in-person assessment included a clinical interview with caregivers. RESULTS: Results indicated diagnostic agreement for 92% of participants. Children diagnosed with ASD following in-person assessment who were missed by tele-assessment (n = 8) had lower scores on tele- and in-person ASD assessment tools. Children inaccurately identified as having ASD by tele-assessment (n = 3) were younger than other children and had higher developmental and adaptive behavior scores than children accurately diagnosed with ASD by tele-assessment. Diagnostic certainty was highest for children correctly identified as having ASD via tele-assessment. Clinicians and caregivers reported satisfaction with tele-assessment procedures. CONCLUSION: This work provides additional support for the use of tele-assessment for identification of ASD in toddlers, with both clinicians and families reporting broad acceptability. Continued development and refinement of tele-assessment procedures is recommended to optimize this approach for the needs of varying clinicians, families, and circumstances.

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4. Cucinotta F, Lintas C, Tomaiuolo P, Baccarin M, Picinelli C, Castronovo P, Sacco R, Piras IS, Turriziani L, Ricciardello A, Scattoni ML, Persico AM. Diagnostic yield and clinical impact of chromosomal microarray analysis in autism spectrum disorder. Molecular genetics & genomic medicine. 2023: e2182.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high heritability estimates and recurrence rates; its genetic underpinnings are very heterogeneous and include variable combinations of common and rare variants. Array-comparative genomic hybridization (aCGH) offers significant sensitivity for the identification of copy number variants (CNVs), which can act as susceptibility or causal factors for ASD. METHODS: The aim of this study was to evaluate both diagnostic yield and clinical impact of aCGH in 329 ASD patients of Italian descent. RESULTS: Pathogenic/likely pathogenic CNVs were identified in 50/329 (15.2%) patients, whereas 89/329 (27.1%) carry variants of uncertain significance. The 10 most enriched gene sets identified by Gene Ontology Enrichment Analysis are primarily involved in neuronal function and synaptic connectivity. In 13/50 (26.0%) patients with pathogenic/likely pathogenic CNVs, the outcome of array-CGH led to the request of 25 additional medical exams which would not have otherwise been prescribed, mainly including brain MRI, EEG, EKG, and/or cardiac ultrasound. A positive outcome was obtained in 12/25 (48.0%) of these additional tests. CONCLUSIONS: This study confirms the satisfactory diagnostic yield of aCGH, underscoring its potential for better, more in-depth care of children with autism when genetic results are analyzed also with a focus on patient management.

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5. De Asis-Cruz J, Limperopoulos C. Harnessing the Power of Advanced Fetal Neuroimaging to Understand In Utero Footprints for Later Neuropsychiatric Disorders. Biological psychiatry. 2023; 93(10): 867-79.

Adverse intrauterine events may profoundly impact fetal risk for future adult diseases. The mechanisms underlying this increased vulnerability are complex and remain poorly understood. Contemporary advances in fetal magnetic resonance imaging (MRI) have provided clinicians and scientists with unprecedented access to in vivo human fetal brain development to begin to identify emerging endophenotypes of neuropsychiatric disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, and schizophrenia. In this review, we discuss salient findings of normal fetal neurodevelopment from studies using advanced, multimodal MRI that have provided unparalleled characterization of in utero prenatal brain morphology, metabolism, microstructure, and functional connectivity. We appraise the clinical utility of these normative data in identifying high-risk fetuses before birth. We highlight available studies that have investigated the predictive validity of advanced prenatal brain MRI findings and long-term neurodevelopmental outcomes. We then discuss how ex utero quantitative MRI findings can inform in utero investigations toward the pursuit of early biomarkers of risk. Lastly, we explore future opportunities to advance our understanding of the prenatal origins of neuropsychiatric disorders using precision fetal imaging.

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6. Dyson A, Ryan M, Garg S, Evans DG, Baines RA. A Targeted, Low-Throughput Compound Screen in a Drosophila Model of Neurofibromatosis Type 1 Identifies Simvastatin and BMS-204352 as Potential Therapies for Autism Spectrum Disorder (ASD). eNeuro. 2023; 10(5).

Autism spectrum disorder (ASD) is a common neurodevelopmental condition for which there are no pharmacological therapies that effectively target its core symptomatology. Animal models of syndromic forms of ASD, such as neurofibromatosis type 1, may be of use in screening for such treatments. Drosophila larvae lacking Nf1 expression exhibit tactile hypersensitivity following mechanical stimulation, proposed to mirror the sensory sensitivity issues comprising part of the ASD diagnostic criteria. Such behavior is associated with synaptic dysfunction at the neuromuscular junction (NMJ). Both phenotypes may thus provide tractable outputs with which to screen for potential ASD therapies. In this study, we demonstrate that, while loss of Nf1 expression within the embryo is sufficient to impair NMJ synaptic transmission in the larva, constitutive Nf1 knock-down is required to induce tactile hypersensitivity, suggesting that a compound must be administered throughout development to rescue this behavior. With such a feeding regime, we identify two compounds from a targeted, low-throughput screen that significantly and consistently reduce, but do not fully rescue, tactile hypersensitivity in Nf1(P1) larvae. These are the HMG CoA-reductase inhibitor simvastatin, and the BK(Ca) channel activator BMS-204352. At the NMJ, both compounds induce a significant reduction in the enhanced spontaneous transmission frequency of Nf1(P1) larvae, though again not to the level of vehicle-treated controls. However, both compounds fully rescue the increased quantal size of Nf1(P1) mutants, with simvastatin also fully rescuing their reduced quantal content. Thus, the further study of both compounds as potential ASD interventions is warranted.

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7. Kang LJ, Huang HH, Wu YT, Chen CL. Initial evaluation of an environment-based intervention for participation of autistic children: a randomized controlled trial. Disability and rehabilitation. 2023: 1-11.

PURPOSE: To evaluate the efficacy of environment-based intervention on participation outcomes and parent efficacy in autistic children. MATERIALS AND METHODS: Twenty-one autistic children 6-10 years old and their parents were randomized to environment-based intervention (n = 11) or usual care (n = 10). The environment-based intervention targets individualized participation goals in leisure and community activities through changing environment and activity demands. The study outcomes were Canadian Occupational Performance Measure (COPM), Goal attainment scaling (GAS), and Parent Empowerment and Efficacy Measure (PEEM). Assessments included baseline, 12 weeks (post-test), and 24 weeks (follow-up). Mixed ANOVAs were used to examine within-group and between-group effects in outcome variables. RESULTS: The COPM performance and satisfaction scores and GAS T-scores increased after environment-based intervention from baseline to 12 weeks and 24 weeks (p < 0.001) but did not significantly differ from usual care. The medium to large effect sizes of COPM performance and GAS T-scores favored the environment-based intervention. For the PEEM scores, no significant differences were found. CONCLUSIONS: Environment-based intervention may support school-age autistic children to participate in self-chosen activities over time. The intervention effects on participation goals and parent efficacy, however, were inconclusive and need further research. Environmental barriers are important attributes to participation restriction in autistic children.Interventions focusing on modifying the task and environment is viable in supporting the participation of autistic children.The environment-based intervention appears to improve the participation goals in leisure and community-based activities over time.The environment-focused strategies may include providing social support, enabling access to a sensory-friendly environment, finding inclusive programs, adapting task demands, and managing routines. eng.

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8. Liu J, Chen L, Chang H, Rudoler J, Belal Ai-Zughoul A, Kang JB, Abrams DA, Menon V. Replicable patterns of memory impairments in children with autism and their links to hyperconnected brain circuits. Biological psychiatry Cognitive neuroscience and neuroimaging. 2023.

BACKGROUND: Memory impairments have profound implications for social communication and educational outcomes in children with autism spectrum disorder (ASD). However, the precise nature of memory dysfunction in children with ASD and the underlying neural circuit mechanisms remain poorly understood. The default mode network (DMN) is a brain network that is associated with memory and cognitive function, and DMN dysfunction is among the most replicable and robust brain signatures of ASD. METHODS: We employed a comprehensive battery of standardized episodic memory assessments and functional circuit analyses in 8-12-year-old 25 children with ASD and 29 matched typically developing controls. RESULTS: Memory performance was reduced in children with ASD, compared to controls. General and face memory emerged as distinct dimensions of memory difficulties in ASD. Importantly, findings of diminished episodic memory in children with ASD were replicated in two independent data sets. Analysis of intrinsic functional circuits associated with the DMN revealed that general and face memory deficits were associated with distinct, hyperconnected circuits: aberrant hippocampal connectivity predicted diminished general memory while aberrant posterior cingulate cortex connectivity predicted diminished face memory. Notably, aberrant hippocampal-posterior cingulate cortex circuitry was a common feature of diminished general and face memory in ASD. CONCLUSIONS: Results represent a comprehensive appraisal of episodic memory function in children with ASD and identify extensive and replicable patterns of memory reductions in children with ASD that are linked to dysfunction of distinct DMN-related circuits. Findings highlight a role for DMN dysfunction in ASD that extends beyond face memory to general memory function.

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9. Lob K, Hou T, Chu TC, Ibrahim N, Bartolini L, Nie DA. Clinical features and drug-resistance in pediatric epilepsy with co-occurring autism: A retrospective comparative cohort study. Epilepsy & behavior : E&B. 2023; 143: 109228.

OBJECTIVE: We conducted a retrospective comparative cohort study to determine the phenotypic and real-world management differences in children with epilepsy and co-occurring autism as compared to those without autism. METHODS: Clinical variables, EEG, brain MRI, genetic results, medical and non-medical treatment were compared between 156 children with both epilepsy and autism, 156 randomly selected and 156 demographically matched children with epilepsy only. Logistic regression analyses were conducted to determine predictors of drug-resistant epilepsy (DRE). RESULTS: As compared to the’matched’ cohort, more patients with autism had generalized motor seizures although not statistically significant after Benjamini-Hochberg correction (54.5%, vs 42.3%, p = .0314); they had a lower rate of electroclinical syndromes (12.8%, vs 30.1%, p = .0002). There were more incidental MRI findings but less positive MRI findings to explain their epilepsy in children with autism (26.3%, vs 13.8% and 14.3%, vs 34.2%, respectively; p = .0003). In addition, LEV, LTG, and VPA were the most common ASMs prescribed to children with autism, as opposed to LEV, OXC, and LTG in children without autism. No difference in the major EEG abnormalities was observed. Although the rates of DRE were similar (24.8%, vs 26.6%, p = .7203), we identified two clinical and five electrographic correlates with DRE in children with both epilepsy and autism and a final prediction modeling of DRE that included EEG ictal findings, focal onset seizures, generalized motor seizures, abnormal EEG background, age of epilepsy onset, and history of SE, which were distinct from those in children without autism. SIGNIFICANCE: Our study indicates that detailed seizure history and EEG findings are the most important evaluation and prediction tools for the development of DRE in children with epilepsy and co-occurring autism. Further studies of epilepsy in specific autism subgroups based on their etiology and clinical severity are warranted.

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10. Manzar S. Maternal infection, prenatal antibiotics, and risk of autism in the offspring. Paediatric and perinatal epidemiology. 2023.

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11. Marcone R, Borghese V. Parental stress and support perception in southern Italy’s households with intellectual disabilities and/or autistic spectrum disorder before and during the COVID-19 pandemic. Research in developmental disabilities. 2023; 138: 104537.

The stress experienced by parents of persons with Intellectual Disability (ID) and Autism Spectrum Disorder (ASD) is higher than that of parents of neurotypical children (TD). An important protective factor is the perception of the support received within the family and the social network. The emergency of the COVID-19 pandemic had a negative impact on the health of people with ASD/ID and their families. The aim of the study was to describe the levels of parental stress and anxiety before and during the lockdown in southern Italy’s families with ASD/ID persons and analyze how the levels of support perceived by these families. 106 parents, the ages of 23 and 74 years (M = 45; SD = 9), from southern Italy responded to an online battery of questionnaires measuring parental stress, anxiety, perception of support and attendance at school activities and rehabilitation centers, before and during lockdown. In addition, descriptive, Chi-Square, MANOVA, ANOVAs, and correlational analyses were conducted. The results showed that during the lockdown, attendance at therapies and extra-moenia activities and participation in school activities drastically dropped. During lockdown, parents felt inadequate. The parental stress and anxiety were moderate, but the perception of support dropped significantly.

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12. Miller JG, Sharifi R, Piccirilli A, Li R, Lee CH, Bartholomay KL, Jordan TL, Marzelli MJ, Bruno JL, Lightbody AA, Reiss AL. Social gaze behavior and hyperarousal in young females with fragile X syndrome: A within-person approach. Development and psychopathology. 2023: 1-12.

Children with fragile X syndrome (FXS) often avoid eye contact, a behavior that is potentially related to hyperarousal. Prior studies, however, have focused on between-person associations rather than coupling of within-person changes in gaze behaviors and arousal. In addition, there is debate about whether prompts to maintain eye contact are beneficial for individuals with FXS. In a study of young females (ages 6-16), we used eye tracking to assess gaze behavior and pupil dilation during social interactions in a group with FXS (n = 32) and a developmentally similar comparison group (n = 23). Participants engaged in semi-structured conversations with a female examiner during blocks with and without verbal prompts to maintain eye contact. We identified a social-behavioral and psychophysiological profile that is specific to females with FXS; this group exhibited lower mean levels of eye contact, significantly increased mean pupil dilation during conversations that included prompts to maintain eye contact, and showed stronger positive coupling between eye contact and pupil dilation. Our findings strengthen support for the perspective that gaze aversion in FXS reflects negative reinforcement of social avoidance behavior. We also found that behavioral skills training may improve eye contact, but maintaining eye contact appears to be physiologically taxing for females with FXS.

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13. Morel C, Martinez Sanchez I, Cherifi Y, Chartrel N, Diaz Heijtz R. Perturbation of maternal gut microbiota in mice during a critical perinatal window influences early neurobehavioral outcomes in offspring. Neuropharmacology. 2023; 229: 109479.

The gut microbiota is increasingly recognized as a key environmental factor that shapes host development and physiology, including neural circuits formation and function. Concurrently, there has been growing concern that early-life antibiotic exposure may alter brain developmental trajectories, increasing the risk for neurodevelopmental disorders such as autism spectrum disorder (ASD). Here, we assessed whether perturbation of the maternal gut microbiota in mice during a narrow critical perinatal window (last week of pregnancy and first three postnatal days), induced by exposure to a commonly used broad-spectrum oral antibiotic (ampicillin), influences offspring neurobehavioral outcomes relevant to ASD. Our results demonstrate that neonatal offspring from antibiotic-treated dams display an altered pattern of ultrasonic communication, which was more pronounced in males. Moreover, juvenile male, but not female, offspring from antibiotic-treated dams showed reduced social motivation and social interaction, as well as context-dependent anxiety-like behavior. However, no changes were observed in locomotor or exploratory activity. This behavioral phenotype of exposed juvenile males was associated with reduced gene expression of the oxytocin receptor (OXTR) and several tight-junction proteins in the prefrontal cortex, a key region involved in the regulation of social and emotional behaviors, as well as a mild inflammatory response in the colon. Further, juvenile offspring from exposed dams also showed distinct alterations in several gut bacterial species, including, Lactobacillus murinus, and Parabacteroides goldsteinii. Overall, this study highlights the importance of the maternal microbiome in early-life, and how its perturbation by a widely used antibiotic could contribute to atypical social and emotional development of offspring in a sex-dependent manner.

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14. Noel JP, Angelaki DE. A theory of autism bringing across levels of description. Trends in cognitive sciences. 2023.

Autism impacts a wide range of behaviors and neural functions. As such, theories of autism spectrum disorder (ASD) are numerous and span different levels of description, from neurocognitive to molecular. We propose how existent behavioral, computational, algorithmic, and neural accounts of ASD may relate to one another. Specifically, we argue that ASD may be cast as a disorder of causal inference (computational level). This computation relies on marginalization, which is thought to be subserved by divisive normalization (algorithmic level). In turn, divisive normalization may be impaired by excitatory-to-inhibitory imbalances (neural implementation level). We also discuss ASD within similar frameworks, those of predictive coding and circular inference. Together, we hope to motivate work unifying the different accounts of ASD.

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15. Xu J, Zhang YJ, Gonzalez E, Dohlman TH, Gaier ED. Eye Swelling and Decreased Vision in a Patient With Autism. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2023; 43(2): e63.

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16. Zahedi E, Sadr SS, Sanaeierad A, Roghani M. Valproate-induced murine autism spectrum disorder is associated with dysfunction of amygdala parvalbumin interneurons and downregulation of AMPK/SIRT1/PGC1α signaling. Metabolic brain disease. 2023.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that is characterized by difficulty in social behavior and restricted behaviors. Also, in ASD, several accompanying disorders such as anxiety are observed. Considering the important role of amygdala in the pathophysiology of ASD, the present study focused on the neuronal changes and it possible signaling pathway in amygdala. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p, on embryonic day 12.5), amount of ROS, MMP, caspase-3 activity, AMPK, SIRT1 and PGC1α proteins, and parvalbumin interneurons in the amygdala were assessed following evaluation of ASD and anxiety-like behaviors. Amygdala analysis revealed ROS accumulation and decreased MMP in autistic rats. In addition, caspase-3 activation elevated and immunoreactivity for parvalbumin interneurons decreased. These were accompanied by anxiety and autistic-like behaviors in open field test, elevated zero maze and U-Shaped 2 Choice Field maze. Also, our data showed that in the valproate group, protein levels of AMPK, SIRT1 and PGC1α reduced. Collectively, our results indicate that prenatal exposure to valproate leads to anxiety and autistic-like behaviors, partly through its targeting amygdala parvalbumin interneurons dysfunction and this might be affected by disturbed AMPK/SIRT1/PGC1α signaling pathway.

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