Autism Research最新文献

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.

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.

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.

Preliminary evidence indicates potential benefit of providing caregiver-mediated intervention, prior to diagnosis, for infants at elevated familial likelihood for autism and related developmental delays including language delay (EL-A). However, delivering such interventions online and in low-resource settings like India has not been reported. This study aimed to evaluate the feasibility and acceptability of delivering a novel manualized caregiver-mediated early support program, the “LiL' STEPS,” online in India, for EL-A infants. LiL' STEPS stands for Language development & Intervention Lab's (LiL') Supporting Early social-communication and language by Promoting caregiver Sensitive responsiveness (STEPS). The program comprised 14 sessions with a focus on social-communication and language, conducted over 12-weeks using demonstration and video feedback. Families of 36 EL-A infants aged 9 to 15-months participated in this feasibility randomized controlled trial (RCT). Families were randomized in a 2:1 ratio (n = 24 LiL' STEPS and n = 12 care as usual groups). Information on feasibility and acceptability was collated following a mixed methods approach from caregiver interviews, fidelity forms, session notes, and study register. Findings indicated the LiL' STEPS study trial as feasible and acceptable with recruitment rate of 4 per month, 100% willingness for randomization, 8.3% attrition, and 3.03% loss of blinding. Interventionist and caregiver fidelity was maintained above 80%. Despite challenges like interruptions during sessions, 100% families found the program acceptable and satisfactory, 86% said they would recommend the program to others, and 71% preferred online modality. Caregivers' perspectives on beneficial components and experience attending the program have been described. Accordingly, recommendations for future definitive RCTs have been presented.

The high co-occurrence of autism and eating disorders is well established, including for those with Avoidant Restrictive Food Intake Disorder (ARFID). It is therefore important to consider autism and identify possible autism when people present to eating disorder services to ascertain whether further assessment is indicated, to support clinical formulation and to make appropriate adaptations during interventions. This paper explores the utility of a validated autism screening measure, the AQ-10, in a population of children and adolescents who presented to an outpatient eating disorders clinic for an assessment of possible ARFID. Over 19 months, 335 young people were assessed and 246 families with children aged between 4 and 17 years completed one of three versions of the AQ-10 (Child, Adolescent, and Adult), as part of a battery of routinely administered pre-assessment questionnaires. Results indicated that 80.2% (n = 69) of those with an existing autism diagnosis scored above clinical threshold of ≥6 (M = 7.2, SD = 1.9), 43.9% (n = 43) of those queried to be autistic scored above clinical threshold (M = 5.2, SD = 2.5), and 6.5% (n = 4) of non-autistic individuals scored above clinical threshold (M = 2.8, SD = 1.8). Additionally, the AQ-10 satisfactorily discriminated between those with a known autism diagnosis and those who are not autistic across all age groups and sex. We conclude that the AQ-10, alongside a comprehensive clinical assessment and clinical judgment, is a useful screening tool that can support clinicians to identify appropriate onward referrals for autism assessments, aid clinical formulation, and consider appropriate adaptations and reasonable adjustments during ARFID interventions.

Some autistic children acquire foreign languages from exposure to screens. Such unexpected bilingualism (UB) is therefore not driven by social interaction, rather, language acquisition appears to rely on less socially mediated learning and other cognitive processes. We hypothesize that UB children may rely on other cues, such as acoustic cues, of the linguistic input. Previous research indicates enhanced pitch processing in some autistic children, often associated with language delays and difficulties in forming stable phonological categories due to sensitivity to subtle linguistic variations. We propose that repetitive screen-based input simplifies linguistic complexity, allowing focus on individual cues. This study hypothesizes that autistic UB children exhibit superior pitch discrimination compared with both autistic and non-autistic peers. From a sample of 46 autistic French-speaking children aged 9 to 16, 12 were considered as UB. These children, along with 45 non-autistic children, participated in a two-alternative forced-choice pitch discrimination task. They listened to pairs of pure tones, 50% of which differed by 3% (easy), 2% (medium), or 1% (hard). A stringent comparison of performance revealed that only the autistic UB group performed above chance for tone pairs that differed, across all conditions. This group demonstrated superior pitch discrimination relative to autistic and non-autistic peers. This study establishes the phenomenon of UB in autism and provides evidence for enhanced pitch discrimination in this group. Acute perception of auditory information, combined with repeated language content, may facilitate UB children's focus on phonetic features, and help acquire a language with no communicative support or motivation.

Theory of Mind has long been studied as a core weakness in autism spectrum disorder due to its relationship with social reciprocity, while bilingualism has been shown to compensate for autistic individuals' mentalizing weaknesses. However, our knowledge of the Theory of Mind developmental trajectories of bilingual and monolingual autistic children, as well as of the factors related to Theory of Mind development in autism spectrum disorder is still limited. The current study has examined first- and second-order Theory of Mind skills in 21 monolingual and 21 bilingual autistic children longitudinally across three time points, specifically at ages 6, 9, and 12, and also investigated associations between Theory of Mind trajectories and trajectories of the children's language, intelligence and executive function skills. The results reveal that bilingual autistic children outperformed their monolingual peers in second-order Theory of Mind at ages 9 and 12, and that intelligence and, especially, expressive vocabulary skills played a pivotal role in advancing bilingual autistic children's second-order Theory of Mind development. On the other hand, monolingual autistic children only managed to capitalize on their language and intelligence resources at age 12. The findings highlight the importance of investigating bilingualism effects on autistic children's advanced cognitive abilities longitudinally.

Although the developmental process of linguistic register—the appropriate manner of speech as determined by the listener and social situation—has been gradually clarified in typically developing (TD) children, research on the mechanism and developmental process of register acquisition in atypically developing children are insufficient. This study compared the developmental process of understanding linguistic register among TD children, autistic children, and those with Williams syndrome (WS), and examined the contributions of social cognition and motivation to the acquisition of linguistic register. Two experiments were designed to assess the recognition of which linguistic register to use when communicating with different listeners and of the listener's feelings according to the speakers' use of register. The results revealed that the process of understanding register-listener associations was nearly identical among all groups of children and their understanding improved with age. Conversely, their understanding of the effect of register selection on the listener's feelings varied. Importantly, as TD children mature, they become aware that adult listeners may feel negatively when spoken to in an inappropriate register, whereas autistic children and those with WS do not exhibit the same awareness. Thus, our results suggest that atypical social cognition and motivation do not disturb the understanding of register-listener associations. However, social cognition and motivation play important roles in understanding the effect of register selection on the listener's feelings. These findings provide a significant contribution to clarifying the mechanism of linguistic register acquisition.