Autism Research最新文献

The autistic community is a large, growing, and heterogeneous population, and there is a need for improved methods to describe their diverse needs. Measures of adaptive functioning collected through public health surveillance may provide valuable information on functioning and support needs at a population level. We aimed to use adaptive behavior and cognitive scores abstracted from health and educational records to describe trends over time in the population prevalence of autism by adaptive level and co-occurrence of intellectual disability (ID). Using data from the Autism and Developmental Disabilities Monitoring Network, years 2000 to 2016, we estimated the prevalence of autism per 1000 8-year-old children by four levels of adaptive challenges (moderate to profound, mild, borderline, or none) and by co-occurrence of ID. The prevalence of autism with mild, borderline, or no significant adaptive challenges increased between 2000 and 2016, from 5.1 per 1000 (95% confidence interval [CI]: 4.6–5.5) to 17.6 (95% CI: 17.1–18.1) while the prevalence of autism with moderate to profound challenges decreased slightly, from 1.5 (95% CI: 1.2–1.7) to 1.2 (95% CI: 1.1–1.4). The prevalence increase was greater for autism without co-occurring ID than for autism with co-occurring ID. The increase in autism prevalence between 2000 and 2016 was confined to autism with milder phenotypes. This trend could indicate improved identification of milder forms of autism over time. It is possible that increased access to therapies that improve intellectual and adaptive functioning of children diagnosed with autism also contributed to the trends.

Neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), have heterogeneous behavioral phenotypes and substantial symptom overlap. Identifying transdiagnostic subgroups may help clarify this heterogeneity. This study aimed to identify behavior-based subgroups of children with NDD and explore links between gastrointestinal (GI) symptoms and behavioral symptoms. Using data from the Province of Ontario Neurodevelopmental Disorders (POND) network, we applied a heterogeneous mixture model (HMM) to behavioral data from 1716 participants, including typically developing (TD, n = 210), ASD (n = 747), and ADHD (n = 759) and identified six distinct clusters. Five of the clusters included individuals with TD, ADHD, and ASD diagnoses. The remaining cluster exhibited the most severe behavior phenotype and was exclusively ADHD and ASD participants. Notably, GI symptoms were significantly more prevalent in the cluster with the most severe behavioral profile (χ² (5) = 64.4, p < 0.0001), which is comparable to previous reports linking GI symptoms to more severe clinical symptoms in NDD. These findings emphasize the importance of considering behavioral dimensions over diagnostic labels to identify NDD subgroups. Further research that focuses on signaling pathways of the gut-brain axis will help understand the biological mechanisms that contribute to individual differences in behavioral profiles in NDDs.

Auditory hypersensitivity is a prominent symptom in Fragile X syndrome (FXS), the most prevalent monogenic cause of autism and intellectual disability. FXS arises through the loss of the protein encoded by the FMR1 (Fragile X Messenger Ribonucleoprotein 1) gene, FMRP, required for normal neural circuit excitability. In the brainstem, FMRP is necessary for normal development of acoustic reactivity, and its loss has been implicated in audiogenic seizures (AGS) in Fmr1 knockout (KO) mice, modeling auditory hypersensitivity and seizures in FXS patients. The present study investigated the correlation between auditory brainstem function and behavioral expression of AGS at the early (postnatal day P20, infancy) and late (P32, juvenile) stages of auditory development in Fmr1 KO mice compared with wildtype (WT) mice, and in both females and males. We tested responsiveness to pure tones of select auditory pathway elements through auditory brainstem responses, and neural synchronization to amplitude envelopes of modulated acoustic stimuli through auditory steady-state responses. AGS behavior was categorized for severity during 5-min exposure to loud sound. Expression of the immediate early gene cFos was quantified as a marker for neuronal activity in the inferior colliculus. During infancy, more severe AGS expression in Fmr1 KO mice compared with WT mice was accompanied by increased responsiveness to acoustic stimuli at the level of the superior olivary complex and inferior colliculus, and stronger neural synchronicity in subcortical auditory neurons. Fmr1 KO mice also had higher cFos positive cell counts in the inferior colliculus after exposure to loud sound. With age, both AGS susceptibility and exaggerated acoustic stimulus-evoked activity in the Fmr1 KO mice subsided. Intriguingly, Fmr1 KO mice displayed an altered developmental profile in both the threshold and amplitude of auditory brainstem response. Our findings support evidence that AGS activity relies upon hyperexcitability in the auditory system, including in the lower brainstem, possibly due to disturbed auditory maturation. Hyper-synchronization to modulated sounds in subcortical auditory neurons seemed to predict AGS severity. The developmental trajectory of the auditory hyperresponsiveness and hypersynchrony suggests a transient processing alteration underlying heightened AGS susceptibility in Fmr1 KO mice. A better understanding of FXS-related circuit and behavioral symptoms of auditory processing across development provides the potential to identify therapeutic strategies to achieve auditory function recovery in FXS.

At least 50% of autistic people experience clinically relevant anxiety symptoms. However, reasons for elevated rates of anxiety in autism remain poorly understood and there is a high unmet need for novel and adapted therapies for anxiety that are accessible to autistic people. This study aimed to establish the feasibility of a novel app-based anxiety management tool (“Molehill Mountain”) that has been developed with, and adapted for, autistic people. A single-centre, single-arm feasibility study design was employed, whereby autistic people (≥ 16 years) with mild-to-severe symptoms of anxiety were recruited to a 13-week intervention period (King's College London, UK; clinicaltrials.gov identifier NCT05302167). Of 123 prospective participants screened, 100 (81%) participants aged 16–74 years (n = 69 female) were enrolled within approximately 15 months. n = 76 (76%) completed an anxiety measure at ~15 weeks (Generalized Anxiety Disorder—7 Item Scale; GAD-7). Most adhered to the full intervention duration: 65% (n = 47), with most using the app weekly (1–6 days per week; 58%). 73% of participants agreed that they found the app easy to use overall and that an app is a good format for offering anxiety support to autistic people. There was a significant reduction in self-reported anxiety symptom severity with mean difference 2.88 (95% CI 1.88, 3.89; p < 0.001; Cohen's d = 0.45). We found that an autism-adapted app-based anxiety management tool is acceptable to the community and associated with reduced anxiety symptom severity in autistic adults, on average. Following optimization to further enhance usability, the efficacy of the Molehill Mountain app for reducing anxiety must now be tested under randomized controlled conditions in a full-scale clinical trial.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication deficits, repetitive behaviors, and sensory abnormalities. Sodium valproate (VPA) exposure during embryonic development is a well-established preclinical model for ASD, leading to increased oxidative stress in the developing brain, including lipid peroxidation, which affects cell proliferation and organization. This study aimed to investigate the potential therapeutic effects of cannabidiol (CBD) and risperidone (RISP) in reversing ASD-like behaviors and associated neurobiological alterations induced by embryonic VPA exposure in a zebrafish model. Zebrafish embryos were exposed to 125 μM VPA for 2 days post-fertilization (dpf). At 3–4 dpf, embryos were treated with 0.06 μM CBD or 1 μM RISP. Behavioral assays were conducted to assess hyperlocomotion and aggressive behavior. At 7 dpf, lipid peroxidation levels were measured, and expression of glial fibrillary acidic protein (GFAP) and calcium/calmodulin (CaM) were analyzed to evaluate neurobiological changes. VPA exposure resulted in increased hyperlocomotion and aggression. CBD treatment effectively reversed these behaviors, while RISP showed limited efficacy. Additionally, CBD reduced lipid peroxidation and restored anandamide levels, whereas RISP did not exhibit these effects. CBD also normalized GFAP and CaM expression, indicating restoration of glial function and excitatory/inhibitory balance. CBD demonstrated a better efficacy and safety profile compared to RISP in reversing ASD-like behaviors and associated neurobiological alterations in the zebrafish model. These findings suggest that CBD may offer a safer and more effective therapeutic alternative for managing ASD-related symptoms.

Autistic adults have increased risks of trauma, suicide, and poor mental health compared to non-autistic adults, with 1 in 4 autistic adults attempting suicide. We administered an anonymized, self-report survey to 424 autistic and 345 non-autistic adults through a convenience sampling framework. Binomial logistic regression models identified whether trauma and autism diagnosis were related to (i) self-harm, (ii) suicide attempts, (iii) suicide plans, (iv) a mental health condition that impacts daily life, and (v) substance use to cope. Heatmaps were generated to identify traumas that frequently co-occur with psychological distress and SRB. After accounting for trauma and demographic differences, autism remained a significant predictor of all outcomes, except whether individuals used substances to cope (OR: 0.78, 95% CI: 0.54–1.12, p = 0.18). Autistic people were more likely to report self-harm (OR: 2.71, 95% CI: 1.85–4.00, p < 0.01), suicide attempts (OR: 2.45, 95% CI: 1.65–3.68, p < 0.01), suicide plans (OR: 2.00, 95% CI: 1.41–2.83, p < 0.01), and experiencing a mental health condition that impacts daily life (OR: 3.58, 95% CI: 2.42–5.33, p < 0.01) than non-autistic people. Among autistic people, childhood victimization co-occurred with a mental health condition that impacts daily life, self-harm, and suicide plans most frequently. This study provides evidence of complex relationships between autism, trauma, self-harm, suicide attempts, suicide plans, and a mental health condition that impacts daily life. Focusing on the prevention of trauma, coping strategies, and recovery from traumatic events through safeguarding and support may be critical tools for suicide prevention among autistic people.