Pubmed du 10/09/25
1. Grumbach P, Kasper J, Hipp JF, Forsyth A, Valk SL, Muthukumaraswamy S, Eickhoff SB, Schilbach L, Dukart J. Local activity alterations in individuals with autism correlate with neurotransmitter properties and ketamine-induced brain changes. Nat Commun;2025 (Sep 9);16(1):8248.
Autism is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition ratio is discussed as a pathomechanism but in-vivo evidence of disturbed neurotransmission underlying functional alterations remains scarce. We compare local resting-state brain activity and neurotransmitter co-localizations between autism (N = 405, N = 395) and neurotypical controls (N = 473, N = 474) in two independent cohorts and correlate them with excitation-inhibition changes induced by glutamatergic (ketamine) and GABAergic (midazolam) medication. Autistic individuals exhibit consistent reductions in local activity, particularly in default mode network regions. The whole-brain differences spatially overlap with glutamatergic and GABAergic, as well as dopaminergic and cholinergic neurotransmission. Functional changes induced by NMDA-antagonist ketamine resemble the spatial pattern observed in autism. Our findings suggest that consistent local activity alterations in autism reflect widespread disruptions in neurotransmission and may be resembled by pharmacological modulation of the excitation-inhibition balance. These findings advance understanding of the neurophysiological basis of autism. Trial registration number: ACTRN12616000281493.
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2. Lee EY, Cho S, Ju R, Kim H, Choi TY, Yoo JH, Joung YS. Development of a Social Communication Intervention Mobile App for Adolescents With Autism Spectrum Disorder and Social Communication Disorder: Protocol for a Pilot Randomized Clinical Trial. JMIR Res Protoc;2025 (Sep 9);14:e66419.
BACKGROUND: Autism spectrum disorder (ASD) and social communication disorder (SCD) are neurodevelopmental disorders characterized by deficits in social communication that hinder social adaptation, with limited pharmacological options for therapy owing to the absence of identified biomarkers. Individuals with ASD or SCD require lifelong interventions tailored to their development stages. However, most existing interventions primarily focus on early childhood, leaving adolescents relatively underserved. Moreover, timely access to interventions is often limited by geographic and economic barriers as specialized clinics and therapists tend to be concentrated in major urban areas. OBJECTIVE: This pilot randomized clinical trial aimed to evaluate the initial safety and efficacy of NDTx-01, a digital therapeutic (DTx) for adolescents with ASD or SCD. NDTx-01 was designed to overcome the accessibility limitations by integrating cognitive behavioral therapy principles, story-based interventions, and gamification elements. METHODS: We introduce a protocol for a multicenter, prospective, assessor-blinded pilot randomized clinical trial involving children and adolescents aged 10 to 18 years diagnosed with ASD or SCD. Participant enrollment was conducted at 3 major medical hospitals. Enrolled participants were randomly assigned to either the intervention group (NDTx-01 and treatment as usual [TAU]) or the control group (TAU only). TAU included medications and therapeutic services. Participants were instructed to use the app approximately 10 minutes per day, 5 days a week. To evaluate the efficacy of NDTx-01, standardized tools were administered, including the Korean version of the Vineland Adaptive Behavior Scales, Second Edition (K-VABS-II); the Social Responsiveness Scale, Second Edition; Clinical Global Impressions-Severity (CGI-S); Clinical Global Impressions-Improvement (CGI-I); the Social Communication Questionnaire; and the Korean version of the Stress Index for Parents of Adolescents. Assessments were conducted in weeks 0, 1, 2, 4, and 6, except for K-VABS-II, CGI-S, and CGI-I, which were administered only in weeks 0, 4, and 6. Statistical analyses were conducted using the SAS software. Between-group differences were assessed using independent 2-tailed 2-sample t tests or Wilcoxon rank sum tests. Within-group changes were evaluated using paired t tests or Wilcoxon signed rank tests. RESULTS: From August 2024 to December 2024, a total of 42 individuals were screened, 39 (93%) participants who met the inclusion criteria were enrolled, and 1 participant withdrew consent; the remaining participants completed the study. The pilot randomized clinical trial was successfully completed, and the results were published in April 2025. As of 2025, we are conducting a confirmatory clinical trial at 5 major hospitals across South Korea. CONCLUSIONS: The results of this pilot clinical trial provided important insights into the initial safety and efficacy of DTx as interventions for adolescents with ASD and SCD. Both groups demonstrated statistically significant improvements in adaptive skills and socialization. TRIAL REGISTRATION: Clinical Research Information Service KCT0009140; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=26713. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/66419.
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3. Scherer N, Kuper H. Urgent need for services to support children with and at risk of developmental disabilities in low- and middle-income countries. Dev Med Child Neurol;2025 (Sep 9)
