Children with visual impairment (VI) are at risk of autism spectrum disorder (ASD); however standard observational diagnostic assessments are not validated for this population. The primary objective of the study is to validate a modified version of the Autism Diagnostic Observation Schedule (ADOS-2®, Module 3), for children with VI. A cross-sectional observational study was undertaken with 100 (mean 5½ years, SD 10.44 months, range 4-7 years; 59 (59%) males) children with congenital disorders of the peripheral visual system with moderate/severe-profound VI. As the primary objective, 83 (83%) who were \'verbally fluent\' were assessed with the modified ADOS-2® (Module 3). Their scores were investigated for reliability, construct and criterion validity against expert clinician formulation and parent-rated social and communication questionnaires (Social Responsiveness Scale-2, SRS-2; Children\'s Communication Checklist-2). The secondary objective with the total sample was to report on frequency and distribution of ASD ratings in this VI population. The modified ADOS-2® (Module 3) was found to have strong internal coherence and construct validity (two factor model) and inter-rater reliability. A new VI diagnostic algorithm was established which showed high sensitivity and specificity against clinician formulation. Using the best cut-off threshold for \'High Risk for ASD\', strong concurrent criterion validity was found according to parent-rated scores on the SRS-2. The modified ADOS-2® (Module 3) was shown to have promising reliability and validity in establishing children at \'High Risk of ASD\' in this vulnerable population. Elevated rates of ASD were found across the sample, in line with previous estimates.

Mothers with asthma or atopy have a higher likelihood of having autistic children, with maternal immune activation in pregnancy implicated as a mechanism. This study aimed to determine, in a prospective cohort of mothers with asthma and their infants, whether inflammatory gene expression in pregnancy is associated with likelihood of future autism. Mothers with asthma were recruited to the Breathing for Life Trial. RNA was extracted from blood samples collected at mid-pregnancy. 300 ng total RNA was hybridized with the nCounter Human Inflammation gene expression panel (Nanostring Technologies, 249 inflammation-related genes). Parents completed the First Year Inventory (FYI) at 12-month follow-up, which assessed an infant\'s likelihood for autism across 2 behavioural domains: social communication and sensory regulation. A total score ≥19.2 indicated increased likelihood for future autism. Inflammatory gene expression was profiled from 24 mothers: four infants scored in the high autism likelihood range; 20 scored in the low autism likelihood range. Six inflammatory genes were differentially expressed and significantly up-regulated in the high autism likelihood group: CYSLTR2, NOX1, C1QA, CXCL10, C8A, IL23R. mRNA count significantly correlated with social communication FYI score for CYSLTR2 (Pearson r = 0.46, p = 0.024) and CXCL10 (r = 0.43, p = 0.036) and with sensory regulation score for ALOX5 (r = -0.43, p = 0.038) and MAFK (r = -0.46, p = 0.022). In this proof-of-concept study, inflammatory gene expression during pregnancy in mothers with asthma was associated with an infant\'s likelihood of future autism as well as scores relating to social communication and sensory regulation.

Parent-mediated, naturalistic developmental behavioral interventions (NDBIs) are a promising approach for supporting social communication development in young autistic children. This study examined the effect of telehealth delivery of a parent-mediated NDBI, Project ImPACT, on children\'s expressive language ability using a randomized control trial with intent-to-treat analysis. Sixty-four young autistic children and their primary caregiver were matched on age and developmental quotient and randomly assigned to receive 6 months of therapist-assisted Project ImPACT (i.e., telehealth coaching), self-directed Project ImPACT, or an active control. Parent-child interactions were recorded at intake and immediately post-treatment, and the children\'s expressive language skills were assessed at intake and a 9-month follow-up using standardized measures. Although there was no total effect of treatment group assignment on child outcomes, a serial mediation analysis revealed that therapist-assisted ImPACT had an indirect effect on children\'s expressive language ability at follow-up through their parents\' use of the intervention strategies and their intentional communication immediately post-treatment. Findings support Project ImPACT\'s program theory and highlight the importance of coaching in achieving positive outcomes when delivered via telehealth.

Although affective irritability is a common and concerning problem for autistic youth, limited research has examined relations among core autism characteristics and irritability. Therefore, this study investigated potential associations among types of restricted/repetitive behaviors (RRBs) and social communication challenges and irritability in autistic children and adolescents. Participants were 107 autistic youth recruited from a university-based autism clinical research program. Two hierarchical multiple regressions were conducted with Affective Reactivity Index as the dependent variable. Covariates were entered at step 1, followed by the independent variables of interest at step 2. For the first model, independent variables of interest were Repetitive Behavior Scale-Revised subscales: stereotyped behavior, self-injurious behavior, compulsive behavior, ritualistic behavior, sameness behavior, and restricted behavior. For the second model, independent variables of interest were Social Responsiveness Scale, Second Edition subscales: social awareness, social cognitive, social communication, and social motivation. Irritability was significantly associated with several categories of RRBs (i.e., insistence on sameness, stereotypic behavior, and restricted interests/activities). Nonetheless, irritability was not associated with categories of social communication and interaction challenges in autistic youth. Results from this study indicated differing associations between core autism characteristics and affective irritability. Findings highlight the importance of differentiating types of restricted, repetitive behaviors and social communication and interaction challenges in conceptualizing mental health concerns in autistic youth.

Recognizing conspecifics is vitally important for differentiating kin, mates, offspring and social threats.1 Although often reliant upon chemical or visual cues, individual recognition across the animal kingdom is also facilitated by unique acoustic signatures in vocalizations.2-4 However, amongst the large Muroidea superfamily of rodents that encompasses laboratory species amenable to neurobiological studies, there is scant behavioral evidence for individual vocal recognition despite individual acoustic variation.5-10 Playback studies have found evidence for coarse communicative functions like mate attraction and territorial defense, but limited finer ability to discriminate known individuals\' vocalizations.11-17 Such a capacity would be adaptive for species that form lifelong pair bonds requiring partner identification across timescales, distances and sensory modalities, so to improve the chance of finding individual vocal recognition in a Muroid rodent, we investigated vocal communication in the prairie vole (Microtus ochrogaster) - one of the few socially monogamous mammals.18 We found that the ultrasonic vocalizations of adult prairie voles can communicate individual identity. Even though the vocalizations of individual males change after cohabitating with a female to form a bond, acoustic variation across individuals is greater than within an individual so that vocalizations of different males in a common context are identifiable above chance. Critically, females behaviorally discriminate their partner\'s vocalizations over a stranger\'s, even if emitted to another stimulus female. These results establish the acoustic and behavioral foundation for individual vocal recognition in prairie voles, where neurobiological tools19-22 enable future studies revealing its causal neural mechanisms.

BACKGROUND: Children with Down syndrome (DS) often need support building language, socialization, and regulation, yet few receive behavioral intervention for this. The Joint Attention, Symbolic Play, Engagement and Regulation (JASPER) intervention holds promise as a clinician-caregiver-mediated approach.
OBJECTIVE: The aims of this pilot study were to (1) describe the behavioral phenotype of children with DS (2) quantify change in child engagement following JASPER receipt, (3) measure caregiver adoption of JASPER strategies, and (4) generate hypotheses and directions for future research.
METHODS: Sixteen toddlers with DS and their caregivers enrolled in the study. Dyads were randomly assigned to one of two conditions: immediate intervention or waitlist control. During the COVID-19 pandemic, intervention was delivered remotely.
RESULTS: Caregivers learned to implement JASPER strategies and pilot data suggest improvements in joint engagement and regulation during play. Case series data show individual heterogeneity of intervention response. Remote intervention delivery may be associated with greater participant retention.
CONCLUSIONS: JASPER may be a viable treatment option to improve joint engagement and emotion regulation in young children with DS. Parents appear receptive to learning and implementing JASPER strategies at home. Remote JASPER delivery may improve participation in research or treatment programs.

Emerging research suggests that music and rhythm-based interventions offer promising avenues for facilitating functional outcomes for autistic individuals. Evidence suggests that many individuals with ASD have music processing and production abilities similar to those of neurotypical peers. These individual strengths in music processing and production may be used within music therapy with a competence-based treatment approach. We provide an updated perspective of how music and rhythm-based interventions promote sensory and motor regulation, and how rhythm and music may then impact motor, social, and communicative skills. We discuss how music can engage and motivate individuals, and can be used intentionally to promote skill acquisition through both structured and flexible therapeutic applications. Overall, we illustrate the potential of music and rhythm as valuable tools in addressing skill development in individuals on the autism spectrum.

Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.

OBJECTIVE: In the context of developmental trajectories, the association between adaptive functioning and core autism symptomatology remains unclear. The current study examines the associations of adaptive behavior with autism symptom sub-domains and with different facets of symptom expression.
METHODS: Participants include 36 children with a recent diagnosis of autism (33 males; mean age = 56.4 months; SD = 9 months). Families were recruited in the context of the Pediatric Autism Research Cohort (PARC) project. Parents filled out questionnaires at two time points, six months apart, regarding their child\'s autism symptoms and adaptive functioning. The longitudinal relationship between adaptive functioning and autism symptoms was investigated using Mixed Linear Model analyses: one assessing the relationship between general symptom levels and adaptive functioning, and another examining the associations between symptom frequency and impact with adaptive functioning. We conducted Pearson correlation tests at both time points to assess the associations between symptom sub-domains and adaptive functioning.
RESULTS: Findings showed that higher autism symptoms associated with lower adaptive behavior skills, and that this association remained stable over time. Autism impact scores did not significantly relate to adaptive skills, as opposed to frequency scores. Associations between adaptive functioning and autism symptom sub-domains strengthened over time.
CONCLUSIONS: These findings suggest that adaptive functioning is associated with parent-report autism symptomatology, and that this association changes and, on average, becomes stronger over time. Findings may indicate that frequency and impact of symptoms have differential roles in the development of adaptive skills and are worthy of further exploration.

COVID-19 required many research teams to shift from in-person to remote assessments, which posed both procedural and theoretical challenges. While research has explored the utility of remote assessments for autism diagnosis from the perspective of families and clinicians, less is known about their application in clinical trials. This paper describes the development of a remote research assessment protocol for a randomized clinical trial focusing on the implementation of reciprocal imitation teaching (RIT) with toddlers in Part C early intervention. This project spans two phases. For Phase 1, our team developed and documented a series of steps utilizing user-centered design (UCD) strategies (e.g., recruiting potential users, creating a prototype, engaging in iterative development) for the purpose of redesigning an assessment protocol for a remote environment. For Phase 2, we examined preliminary outcomes of the redesign process. Primary end users (assessors) rated post-redesign usability and acceptability, while acceptability was examined using attrition data from secondary end users (family participants). Preliminary fidelity of implementation was also examined. The iterative redesign process allowed the research team to refine aspects of the assessment that ultimately led to promising preliminary ratings of usability, acceptability, and feasibility, as well as high fidelity. Preliminary data suggest that the redesigned assessment appears to be an acceptable, feasible, and usable tool for autism clinical trial research and that assessors can use it with fidelity. Further research is needed to examine the reliability and validity of the assessment, as well as implementation characteristics on a larger scale.