Autism Research最新文献

The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980–2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5.

While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and nongenetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity.

Autistic children, as well as their primary caregivers (e.g., parents), experience greater health disparities when compared with the general population. Despite this reality, there has been relatively little priority placed on promoting positive trajectories of health in either of these underserved populations. The primary purpose of this study was to examine the impact of participation in a 12-month, longitudinal health promotion program designed for both autistic children and their parent. A total of 27 families participated in the intervention, including 29 autistic children (83% male, M = 8.28 ± 3.60 years) and 27 parents (93% female, M = 40.04 ± 7.95). Families attended in-person health promotion programming for 90 min per week. Children and parents were evaluated at four time points across the program, including baseline (0-months), 4-months, 8-months, and 12-months. Children were measured on fundamental motor competence, physical fitness, body composition, and proxy-reported physical activity. Parents were measured on body composition, physical fitness, and self-reported physical activity. Significant improvements were observed for autistic children in motor competence (p < 0.001) and grip strength (p = 0.006), and for parents in body mass index (p = 0.004) and aerobic capacity (p = 0.003) across the 12-month intervention. Differing trajectories of improvement were noted between urban- and suburban-dwelling families on multiple outcomes. The knowledge acquired from this research may offer initial support for the need to bolster opportunities for accessible and ongoing health promotion programs for both autistic children and their parents.

Autistic individuals exhibit differences in their use and understanding of nonverbal communication; however, individual patterns of nonverbal strengths and challenges vary significantly. This heterogeneity can complicate the diagnostic and screening processes and can result in delayed or missed diagnoses. In this study, we characterize various profiles of nonverbal communication skills among 215 pre-verbal children with autism (M_age = 36.27 months, range = 18–70) and explore how these profiles are related to screening outcomes, diagnostic certainty, and developmental and behavioral features. We conducted a latent class analysis of nine items assessing nonverbal communication skills from the Toddler Module and Module 1 of the Autism Diagnostic Observation Schedule, 2nd Edition. Five nonverbal profiles were identified that differentiated children based on the form, function, and frequency of their nonverbal communication skills. Furthermore, screening outcomes and clinician certainty in autism diagnosis varied by nonverbal profile. False negative screening outcomes based on parent report were highest for children who used a range of nonverbal skills but with limited frequency or consistency. Clinicians, on the other hand, tended to have high certainty in an autism diagnosis for children with this profile, and instead rated their lowest certainty in diagnosing children who demonstrated consistent integration of eye contact with their nonverbal communication. The profiles identified in this study could be clinically useful in helping to identify children at highest likelihood of being overlooked during the screening or diagnostic processes, providing an opportunity to improve early identification and intervention for autism.

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease-modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting-motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short-intracortical inhibition, a marker of GABAa-mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379).

Sex heterogeneity has been frequently reported in autism spectrum disorders (ASD) and has been linked to static differences in brain function. However, given the complexity of ASD and diagnosis-by-sex interactions, dynamic characteristics of brain activity and functional connectivity may provide important information for distinguishing ASD phenotypes between females and males. The aim of this study was to explore sex heterogeneity of functional networks in the ASD brain from a dynamic perspective. Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were analyzed in 128 ASD subjects (64 males/64 females) and 128 typically developing control (TC) subjects (64 males/64 females). A sliding-window approach was adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic functional connectivity (dFC) to characterize time-varying brain activity and functional connectivity respectively. We then examined the sex-related changes in ASD using two-way analysis of variance. Significant diagnosis-by-sex interaction effects were identified in the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and left precuneus in the dALFF analysis. Furthermore, there were significant diagnosis-by-sex interaction effects of dFC variance between the left ACC/mPFC and right ACC, left postcentral gyrus, left precuneus, right middle temporal gyrus and left inferior frontal gyrus, triangular part. These findings reveal the sex heterogeneity in brain activity and functional connectivity in ASD from a dynamic perspective, and provide new evidence for further exploring sex heterogeneity in ASD.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2 weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3 weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders.

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.

This study aims to assess the prevalence of Autism Spectrum Disorder (ASD) and its treatment. The study population was children aged 3–17 years with information on current ASD from National Survey of Children's Health, 2016–2022. Analysis of treatment was also conducted within the population of children with a current ASD diagnosis. A multivariate log-binomial regression model was used to assess the change of current ASD prevalence and ASD treatment by two study period (prior to COVID-19 pandemic: 2016–2019; during COVID-19 pandemic: 2020–22) and sociodemographic information. Compared to the current ASD at 2.5% in 2016, it increased to 3.6% in 2022. The treatment has decreased from 70.5% in 2016 to 61.6% in 2022 for any treatment and from 27.2% in 2016 to 20.4% in 2022 for medication treatment. Compared to children from 2016–2019, children from the following group were more likely to have ASD diagnosis during the pandemic (2020–2022), including those aged 3–5 years (aPR = 1.66, 95%CI 1.29–2.13), non-Hispanic white children, children from family with above national family income, and those with private insurance. However, medication treatment almost halved during the pandemic for non-Hispanic black children (aPR = 0.49, 95%CI 0.26–0.93) and children born overseas. In conclusion, higher prevalence of ASD might indicate a better awareness of ASD. The reduction in treatment correlates to the health service disruption caused by the pandemic, highlighting the needs of policy efforts to improve treatment for ASD.

Transitive inference (TI) has a long history in the study of human development. There have, however, few pediatric studies that report clinical diagnoses have tested trial-and-error TI learning, in which participants infer item relations, rather than evaluate them explicitly from verbal descriptions. Children aged 8–10 underwent a battery of clinical assessments and received a range of diagnoses, potentially including autism spectrum disorder (ASD), attention-deficit hyperactive disorder (ADHD), anxiety disorders (AD), specific learning disorders (SLD), and/or communication disorders (CD). Participants also performed a trial-and-error learning task that tested for TI. Response accuracy and reaction time were assessed using a statistical model that controlled for diagnostic comorbidity at the group level. Participants in all diagnostic categories showed evidence of TI. However, a model comparison analysis suggested that those diagnosed with ASD succeeded in a qualitatively different way, responding more slowly to each choice and improving faster across trials than their non-ASD counterparts. Additionally, TI performance was not associated with IQ. Overall, our data suggest that superficially similar performance levels between ASD and non-ASD participants may have resulted from a difference in the speed-accuracy tradeoff made by each group. Our work provides a preliminary profile of the impact of various clinical diagnoses on TI performance in young children. Of these, an ASD diagnosis resulted in the largest difference in task strategy.

Children with autism spectrum disorder (ASD) show impairments in response inhibition, especially in socio-emotional contexts. A single aerobic exercise session has the potential to temporarily reduce such impairments as findings from neurotypical children support acute benefits of this exercise type for inhibitory control and emotion recognition. In children with ASD, we therefore aimed to investigate the effects of an aerobic exercise bout on response inhibition in an emotional Go/NoGo task and gaze fixation as possible mechanism underlying changes in performance. Using a cross-over design, 29 patients completed a 20-min aerobic exercise bout at moderate intensity on a cycling ergometer and a control condition in a randomized order. An emotional Go/NoGo task was administered before and after both experimental conditions. Eye-tracking was performed during the cognitive task to assess the duration of gaze fixation of eyes and mouth parts of faces expressing happy or sad emotions. The results support no beneficial effect of exercise on performance on the emotional Go/NoGo task. Instead, patients showed a greater decrease in accuracy on Go trials displaying happy faces in the exercise compared to the control condition. This change was associated with a more pronounced decrease in the fixation duration of the eyes for faces expressing either happy or sad emotions. In conclusion, while a single session of moderately intense aerobic exercise does not affect response inhibition, it temporarily aggravates ASD-specific deficits in the processing of and response to facial emotions.