Pubmed du 10/10/25
1. Black MH, Segers J, Moormann E, Torell S, Ingard C, Bölte S. A qualitative study of risk and resilience for positive life outcomes in neurodivergence using the WHO ICF. Sci Rep. 2025; 15(1): 35285.
Resilience is a dynamic process involving the interaction of multi-systemic individual and environmental factors that operate to protect against adversity and promote positive personal outcomes. Resilience is a topic of interest among groups who commonly experience adversity. Yet, it has received limited attention in the context of neurodivergence (e.g., autism and Attention Deficit Hyperactivity Disorder). This study is part of a larger project investigating the bio-psycho-social factors contributing to resilience in neurodivergence using the World Health Organization’s International Classification of Functioning (ICF). Interviews and focus groups were conducted with 69 neurodivergent individuals and/or their loved ones to explore the factors they believe influence risk and resilience for positive life outcomes and well-being. A deductive qualitative content analysis was employed to extract meaningful concepts from the interviews, which we then quantified by linking concepts to the ICF. A range of bio-psycho-social factors contributing to risk and resilience were identified, particularly in the ICF’s activity, participation, and environmental domains. Key factors included the immediate family, friends, and community members, as well as recreation and leisure, higher-level cognitive functions, and empowerment. Findings, while preliminary, highlight the need to look beyond individual factors alone, emphasizing the variable and context-dependent nature of resilience in neurodivergence.
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2. Haque MS, Islam MM, Khan AH, Akter N, Hossain KMA. Efficacy of physiotherapy with occupational and speech therapy for improving physical & behavioral status among children with autism spectrum disorder (ASD): an assessor blinded randomized clinical trial. BMC Pediatr. 2025; 25(1): 798.
BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by physical, communication, and behavioral challenges that often require comprehensive interventions. This study aimed to evaluate the combined efficacy of physiotherapy, occupational and speech therapies in improving physical and behavioral outcomes among children with ASD. MATERIALS AND METHODS: This assessor-blinded randomized clinical trial was conducted at Proyash (Institute of Special Education), Jashore, Bangladesh, involving seventy children with ASD. Outcomes were assessed using the modified SF-36 for physical status and GARS-3 for behavioral status at baseline and after six weeks of intervention. Data were analyzed using SPSS version 25.0, with descriptive statistics (median and IQR) and inferential tests (Mann-Whitney U and Wilcoxon signed-rank), maintaining a 95% confidence level. RESULTS: The average age of participants was 10.66 ± 3.28 years in Group A and 9.17 ± 2.83 years in Group B. Group A had a higher BMI of 21.86 ± 7.96 kg/m² compared to 19.53 ± 4.85 kg/m² in Group B. Post-intervention analysis revealed significant improvements in both physical and behavioral outcomes. Between-group comparisons yielded p-values < 0.01 for both measures. Within-group analysis showed significant improvements in Group A (p < 0.01), whereas changes in Group B were not statistically significant. CONCLUSION: The combined rehabilitation program demonstrated significant improvements in physical and behavioral outcomes and showing greater effectiveness overall. These findings emphasize the importance of customized rehabilitation approaches in enhancing both physical and behavioral health, particularly when tailored to specific participant profiles. TRIAL REGISTRATION: CTRI/2024/07/070209 (Prospectively Registered).
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3. Ilyka D, Jiang Y, Begum-Ali J, Mason L, Gui A, Gliga T, Lloyd-Fox S, Jones E, Charman T, Johnson MH. Mutual gaze and later social attention development in infants at typical and elevated familial likelihood for ASD and/or ADHD. Early Hum Dev. 2025; 211: 106398.
Atypical social attention is a feature of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), yet this has not yet been studied during toy-free naturalistic parent-infant interactions in infants at elevated likelihood of developing ADHD (EL-ADHD). We coded mutual gaze from caregiver-infant free-play videos recorded at 4-7 months in infants with typical likelihood (TL; n = 37), elevated likelihood of ASD (EL-ASD; n = 55), ADHD (EL-ADHD; n = 13) or both (EL-ASD + ADHD; n = 13). Face-orienting responses were measured using an eye tracking face pop-out task at 8-12 months, and ASD research diagnosis was established at 36 months. Results showed that EL groups engaged in more mutual gaze than TL peers, revealing a broad alteration in dyadic attention across neurodevelopmental likelihood. However, mutual-gaze duration did not differentiate infants who were later given an ASD diagnosis at age 3 years (n = 14). Furthermore, only in the EL-ASD group greater early mutual gaze predicted reduced subsequent orienting to faces. This association was mainly driven by those diagnosed with ASD at age 3, potentially indicating an ASD-specific developmental pathway. These findings highlight the value of naturalistic paradigms for probing early social attention and the need for larger, jointly analysed EL-ASD and EL-ADHD cohorts to refine neurodevelopmental models of typical and atypical infant social attention.
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4. Liang SF, Ming Y, Huang HT, Lo RY, Chompoopong S, Chen CC, Liu IY. Activation of GABA transmission by clonazepam reverses the autistic-like phenotypes of the Cav3.2 knockout mice. Neurotherapeutics. 2025: e00761.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits, accompanied by restricted and repetitive behaviors. ASD is a lifelong condition that causes a heavy medical and societal burden. To date, there are no disease-modifying, mechanism-targeted treatments approved for core ASD symptoms. In human studies, loss-of-function mutations in the CACNA1H gene, which encodes the T type Cav3.2 calcium channel, have been associated with ASD. However, animal and molecular studies investigating the underlying mechanism in ASD patients with CACNA1H mutations are lacking. In this study, we performed a series of behavioral assays to phenotype the Cav3.2 systemic knockout (Cav3.2KO) mice. The Cav3.2KO mice exhibited ASD-like behaviors, including impaired social novelty, increased self-grooming behavior, and deficits in recognition and retrieval of fear memory. Notably, enhancing γ-aminobutyric acid (GABA) signaling via administration a low-dose of clonazepam (CLZ) rescued these behavioral impairments in the Cav3.2KO mice. Furthermore, we found that the intrinsic GABA level was significantly reduced in the frontal cortex of Cav3.2KO mice, suggesting that GABA transmission was impaired in the Cav3.2KO mice. Together, our findings suggest that loss-of-function in the Cav3.2 channel contributes to ASD-like phenotypes through disrupted GABAergic signaling and that pharmacological enhancement of GABAergic signaling may offer a potential therapeutic approach for individuals with ASD carrying the CACNA1H mutations.
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5. Procopiou G, Jackson PJM, di Mascio D, Auer JL, Andriollo P, Pysz-Hosey I, Mantaj J, Rahman KM, Fox KR, Thurston DE. Synthesis, SAR, and biophysical mechanism of action of cyclopropabenzindole-pyridinobenzodiazepine (CBI-PDD) guanine-adenine DNA cross-linking agents. Eur J Med Chem. 2025; 301: 118196.
This study investigates the Structure-Activity Relationship (SAR) and biophysical mechanism of action of a series of novel Cyclopropabenzindole-Pyridinobenzodiazepine (CBI-PDD) agents designed to alkylate adenine and guanine bases in the DNA minor groove. A library of 18 analogs was synthesized using a modular approach to vary linker length, rigidity and the CBI and PDD core structures. Structural modifications included alkyl, aromatic, heteroaromatic and sterically constrained linkers, as well as prodrug variants. Several compounds demonstrated potent in vitro cytotoxicity, with lead analogs achieving IC(50) values in the low picomolar range across multiple human tumor cell lines. Control compounds with inactivated electrophilic groups in either or both pharmacophores showed markedly reduced activity, confirming the necessity of dual alkylation for optimal cytotoxic potency. Fluorescence-based thermal denaturation (ΔT(m) up to 34 °C) and gel-based assays were used to assess DNA binding and provide mechanistic insights into the DNA sequence requirements for mono-alkylation and interstrand cross-linking. The study also includes a scalable synthesis of a linker-payload construct suitable for Antibody-Drug Conjugate (ADC) applications based on these agents. Overall, these findings support the use of CBI-PDDs as a promising class of sequence-selective DNA cross-linking agents for targeted cancer therapies.
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6. Zhao MM, Hashimoto K, Yang JJ. Early-life microbiota dysbiosis as a link between Autism Spectrum Disorder and Parkinson’s Disease. Mol Psychiatry. 2025.
