Pubmed du 10/07/25
1. Amalia R, Indreswari H, Widiastuti AA. Universal or contextual? Rethinking brain structure-function links in autism through cross-cultural lenses. Brain Imaging Behav;2025 (Jul 10)
Lien vers le texte intégral (Open Access ou abonnement)
2. Choi H, Ju HJ, Sung C. Meta-Analysis of Soft Skills Interventions for Transition-Age Autistic Individuals. Autism Res;2025 (Jul 10)
There has been growing interest in developing and evaluating soft skills interventions for transition-age autistic individuals. While many interventions demonstrated effectiveness in improving social competence, there is limited evidence on the pooled effectiveness of these interventions. In response to the research gap, this study aimed to investigate the effectiveness of soft skills interventions in enhancing social competence among transition-age autistic individuals. A total of 18 articles consisting of eight randomized controlled trials and 10 pre- and post-intervention studies were identified after a systematic review, and the effectiveness of these interventions was examined using the meta package on R 4.4.1. The analysis revealed overall positive effects of soft skills interventions in social adjustment (g = 0.53, p < 0.0001), social performance (g = 0.87, p < 0.001), and social skills (g = 0.53, p < 0.0001) among the autistic individuals. Moderation analyses indicated no significant impact of sample and intervention characteristics on soft skills outcomes. This meta-analysis highlights the importance of soft skills interventions for transition-age autistic individuals in preparing for successful careers.
Lien vers le texte intégral (Open Access ou abonnement)
3. Coburn KL, Shipley EP. « Do I Need Anything More Specific? »: Experiences of Autistic Participants in a Language-Focused Research Study. Am J Speech Lang Pathol;2025 (Jul 10);34(4):1967-1977.
BACKGROUND: Autistic advocates have called for researchers to engage with the needs and experiences of autistic people when planning and designing research studies. The purpose of the present study was to better understand the experiences of autistic adults participating in a language research study and how researchers can design more accessible future studies. METHOD: The present study was a secondary thematic analysis of data recorded during a larger study of spoken narratives by autistic adults. During virtual research interviews, participants frequently expressed comments about the nature of the research tasks and their experiences of participation in the study. The full interview transcripts were analyzed to identify data relating to participants’ subjective experiences of research participation. Thematic analysis was applied to transcripts of all comments not directly elicited by the structured narrative prompts. RESULTS: Four main topics and their subthemes were established based on analysis of the data set: processing strategies, attitudes toward research, awareness of the research process, and self-reflective comments about the narrative tasks. The main topics and their subthemes are discussed to derive insight into the experiences of autistic research participants. DISCUSSION: The findings are especially relevant to researchers and practitioners who conduct spoken language tasks with autistic people. To make research participation more accessible and affirming for autistic people, researchers can share specific information about what to expect before, during, and after participation.
Lien vers le texte intégral (Open Access ou abonnement)
4. Feng S, Wang M, Zhang J, Ding L, Yuan Y, Zhang P, Bai X. Attraction through similarity in autistic traits: A group communication study using social relations model and fNIRS hyperscanning. Biol Psychiatry;2025 (Jul 7)
BACKGROUND: The double empathy problem (DEP) reconceptualizes autism’s social challenges as bidirectional differences rather than unidirectional deficits. Following the DEP, the dialectical misattunement hypothesis (DMH) predicts that interaction between people with similar autistic traits will be smoother and reflected in neural synchronization. However, evidence remains inconsistent due to methodological limitations in dyadic designs and unstructured tasks, and it remains unclear whether neural mechanisms differ between passive and active social contexts across autistic trait levels. METHODS: Using the social relations model, we measured the relational attraction within four-person groups (20 female and 10 male groups), composed of two high-autistic-trait individuals and two low-autistic-trait individuals following a turn-taking discussion. Simultaneously, we recorded brain activity using functional near-infrared spectroscopy (fNIRS) during both passive story listening and active turn-taking discussion. RESULTS: Individuals with similar autistic traits reported higher interpersonal attraction when sharing consistent opinions. Neural analyses revealed context-dependent interbrain coupling patterns: During passive story listening, low-autistic-trait dyads exhibited higher inter-subject correlation (ISC) compared to high-autistic-trait dyads. In contrast, during active communication, low-autistic-trait dyads exhibited higher interbrain synchronization (IBS) in the right temporoparietal junction, while high-autistic-trait dyads showed higher IBS in the right dorsolateral prefrontal cortex, suggesting distinct neural mechanisms underlying social interaction across autistic trait levels. CONCLUSIONS: Our findings support the DMH and reveal that neural synchronization mechanisms vary across both autistic trait levels and social contexts. These context-dependent patterns challenge deficit-based models of autism, suggesting that high-autistic-trait individuals may employ alternative but effective neural strategies during social interaction, particularly in active communication contexts.
Lien vers le texte intégral (Open Access ou abonnement)
5. Gangi DN, Iosif AM, Maqbool S, Hill MM, Parikh C, Young GS, Ozonoff S. Continuity in social communication development among school-aged siblings of autistic children. Dev Psychol;2025 (Jul 10)
Prospective studies of later born siblings of autistic individuals often focus on predicting autism diagnosis. Studies concentrating on siblings who do not develop autism have found subclinical atypicalities in some children as early as the first year of life. However, when followed to school-age, the continuity of these findings has been mixed. We tracked nonautistic siblings (n = 151 higher familial likelihood of autism, n = 115 lower likelihood) longitudinally from infancy to 6-16 years of age when participants completed a battery of social communication measures (parent report and direct observation/administration). Using latent profile analysis, we derived groupings based on patterns of performance across measures. Three groups were identified: Class 1 (45.5%), Class 2 (45.2%), and Class 3 (9.3%)-characterized by higher, intermediate, and lower school-age social communication abilities, respectively. We then examined the performance of these classes on independent measures of pragmatic language, reciprocal social interaction, and cognition. Class 3 demonstrated social communication differences that were most evident with novel interactive partners (e.g., examiners) and scored lower on IQ and academic achievement measures, indicating that social communication differences captured by the latent profile analysis were part of a broader pattern of developmental differences. Using data collected in the first 3 years of life, we found that the school-age classes began showing differences by 12-18 months of age-evidence of continuity between early behavior and later development. Findings suggest that when early childhood challenges are observed in siblings of autistic children, even those not meeting criteria for autism, they should be monitored over time and additional support offered as needed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Lien vers le texte intégral (Open Access ou abonnement)
6. Gulzar MM, Sarani ZA, Tariq M, Knerr I. 3-methylcrotonyl-CoA carboxylase deficiency in a child with developmental regression and delay: call for early diagnosis and multidisciplinary approach. BMJ Case Rep;2025 (Jul 10);18(7)
3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency (3-MCC-D) is an autosomal recessive disorder with a variable phenotype. Reduced 3-MCC enzyme activity results in impaired leucine metabolism causing, for example, metabolic acidosis, ketotic hypoglycaemia and carnitine deficiency. The spectrum of clinical presentation is wide, ranging from severe early-onset presentations to incidental findings in asymptomatic individuals. This report describes the case of a young girl who underwent dramatic developmental regression at 11 months of age, following a respiratory tract infection. Metabolic investigations revealed high excretions of urinary 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, consistent with 3-MCC-D. Treatment was commenced immediately, including carnitine, biotin and moderate dietetic modifications. Molecular genetic investigations confirmed compound heterozygosity for two pathogenic variants in the MCCC1 gene, Trp358Cysfs*13 and duplication of exons 2 and 3. Now in middle childhood, the girl is meeting all her developmental milestones and has had no metabolic decompensation in 6 years of follow-up.
Lien vers le texte intégral (Open Access ou abonnement)
7. Halvorsen MB, Kildahl AN, Thimm JC, Helverschou SB. Structural Validity of the Psychopathology in Autism Checklist Among Children and Adolescents. J Intellect Disabil Res;2025 (Jul 10)
BACKGROUND: The use of instruments developed for people with autism spectrum disorder (ASD) and intellectual and developmental disabilities (IDDs) is recommended for assessing mental health in these groups. This is the first study to investigate the structural validity and internal consistency of the Psychopathology in Autism Checklist (PAC) among autistic children and adolescents with IDDs. METHODS: A total of 600 children aged 2-19 years (M = 9.2 years, SD = 4.5 years, 66% male) with IDDs (full-scale IQ M = 81.29, SD = 18.65) participated, including 194 individuals with ASD. Parents completed the PAC, Strengths and Difficulties Questionnaire (SDQ) and Vineland Adaptive Behaviour Scales (VABS). Full-scale IQ was assessed using an individualised intelligence test, and the extent of autism characteristics was assessed using the Autism Diagnostic Observation Schedule-2. RESULTS: Confirmatory factor analyses revealed acceptable fit indices for a three-factor solution. The internal consistency was adequate for most of the PAC subscales. The PAC showed meaningful overlap and differentiation with the SDQ, VABS, measures of intellectual functioning and a measure of autism symptoms. CONCLUSIONS: Overall, satisfactory internal consistency and validity were found for the PAC (with the exception of the psychosis subscale). These findings provide preliminary support for the use of the PAC in children and adolescents with ASD and IDDs.
Lien vers le texte intégral (Open Access ou abonnement)
8. Hart LC, Sirrianni J, Rust S, Hanks C. Varying Effects of Antipsychotics and Attention-Deficit Hyperactivity Disorder Medications on Body Mass Index among a Cohort of Autistic Youth. J Pediatr Clin Pract;2025 (Sep);17:200159.
OBJECTIVE: Autistic adolescents and young adults (AYAs) are more likely to be obese than nonautistic peers. They are also more likely to be on psychiatric medications that can influence weight. The transition to adult health care is a challenge for autistic AYAs. The extent to which medications and transfer to adult care influence the weight of autistic youth is not well described. STUDY DESIGN: We assessed changes in body mass index (BMI) over time among a cohort of 216 autistic AYAs who had transferred from a pediatric hospital to an adult primary care clinic for autistic AYAs. We compared the mean BMI before and after transfer and used linear regression with main effects and age-related interaction terms to evaluate the contribution of transfer and psychiatric medications on BMI over time. RESULTS: We found that mean BMI increased over time and that age and transfer to adult care both appeared to be drivers of BMI increases. We also found that psychiatric medications had complex effects on weight over time. For example, medications for attention-deficit hyperactivity disorder were associated with a lower BMI at age 16, but showed interaction with age such that each year of increased age beyond 16 mitigated the BMI decrease at age 16. CONCLUSIONS: These findings highlight the importance of evaluating for changes in side effects of medicines over time, particularly during the transition to adult care and support other calls to address healthy eating and activity habits with autistic AYAs in adolescence.
Lien vers le texte intégral (Open Access ou abonnement)
9. He Y, Li J, Zheng W, Liu J, Dong Z, Yang L, Tang S, Zou Y, Gao T, Yang Y, Mo Z, Wang S, He Y, Tang C, Luo J, Zhao J, Guo G, Li H, Xiao L. Hypomyelination in autism-associated neuroligin-3 mutant mice impairs parvalbumin interneuron excitability, gamma oscillations, and sensory discrimination. Nat Commun;2025 (Jul 10);16(1):6382.
Whether and how myelin plasticity, an emerging new form of brain plasticity, is involved in autism spectrum disorder (ASD) remains unknown. Here, we identify deficits in oligodendrocyte (OL) generation and myelination in the barrel cortex (BC) of the male NL3-R451C-KI mouse model of ASD. These mice also show impaired texture recognition, disrupted gamma neuronal oscillations, and reduced excitability and myelination level in the BC-PV interneuron. These abnormalities can be rescued by a promyelinating strategy and are recapitulated by genetic blockade of myelination in Myrf-cKO mice. Furthermore, OL progenitor-specific conditional NL3 knockout mice show similar deficits in BC-PV interneuron myelination and excitability, as well as neuronal oscillation and texture recognition, closely resembling the NL3-R451C-KI phenotype. Collectively, these results demonstrate that NL3 mutations commonly cause hypomyelination and reduced excitability in BC-PV interneurons, disrupting neuronal oscillation and contributing to ASD-like sensory dysfunction. Our finding reveals a mechanism underlying ASD and highlights OLs/myelin as potential therapeutic targets for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
10. Hidema S, Nishimori K, Otsuka A, Horiai M, Mizuno K, Ono T, Maejima Y, Shimomura K. Kamikihito ameliorates social recognition in oxytocin gene deficient mice and environmentally induced autism spectrum disorder model mice. J Ethnopharmacol;2025 (Jul 10):120263.
ETHNOPHARMACOLOGICAL RELEVANCE: Kamikihito (KKT) is a traditional Japanese medicine used to treat insomnia, anemia, anxiety and neurosis. Its scientific mechanism of action is not well understood. AIM OF THE STUDY: This study aimed to evaluate the therapeutic effect of KKT on deficits in social recognition ability, a phenotype of autism spectrum disorder (ASD), and to investigate the involvement of oxytocin in its action. MATERIALS AND METHODS: KKT was orally administered to wild-type (WT), Oxytocin knockout (Oxt (-/-)), and Oxt receptor knockout (Oxtr (-/-)) mice, and social recognition ability was assessed using a three-chamber test. Neuronal activation changes in the brain after social stimulation were evaluated using c-Fos immunostaining in WT, Oxt (-/-), and Oxt (-/-) mice treated with KKT. Additionally, we examined whether KKT ameliorates social recognition impairment in LPS-induced ASD model mice (LPS mice), where LPS serves as an environmental factor. RESULTS: Abnormal social recognition behavior was improved in the Oxt (-/-) mice after sustained KKT administration, but not in the Oxtr (-/-) mice. c-Fos immunostaining revealed excessive neural activation of the Oxt (-/-) mice following social stimulation, which was reduced to WT levels after KKT administration. Social recognition impairment in the LPS mice was improved by KKT. CONCLUSION: Our results suggest that KKT may improve social recognition by acting through Oxtr and by suppressing excessive neural activation after social stimulation. These effects may represent part of KKT’s mechanism of action. It is possible for KKT to become a commonly used treatment for ASD-like symptoms.
Lien vers le texte intégral (Open Access ou abonnement)
11. Horne RSC, Yee AK, Siriwardhana LS, Walter LM, Wong FY. Long Term Developmental Consequences of Short Apneas and Periodic Breathing in Preterm Infants. Pediatr Pulmonol;2025 (Jul);60(7):e71193.
OBJECTIVE: Preterm infants frequently experience short apneas which can occur in isolation or in a repetitive pattern termed periodic breathing. We assessed the consequences of the amount of time spent with short apneas on developmental outcomes at 2 years of age. METHODS: Preterm infants (N = 23) born between 28 and 32 weeks gestational age were studied during daytime sleep in the supine position at 32-36 weeks post menstrual age (PMA), 36-40 weeks PMA, 3 months and 6 months corrected age. The percentage of total sleep time (TST) spent with apneas at each study was calculated. Infants were divided into those below and above the median cumulative time spent with apneas over the 4 studies (28.4% TST) and developmental assessments (Bayley Scales of Infant Development III, Early Childhood Behavior Questionnaire, Child Behavior Check List) at 2 years of age were compared with ANCOVA. RESULTS: The above median group tended to have lower unadjusted scores for motor composite, social emotional composite and adaptive behavior composite on the Bayley’s. After adjusting for confounders and %TST spent with apneas, the motor composite score was significantly lower in the above median group (p < 0.05). Perceptual Sensitivity was lower in the above median group (p < 0.05). CONCLUSIONS: In clinically stable very preterm infants, who had been discharged home with no concerns of respiratory instability, those infants who spent more time with short apneas, particularly periodic breathing, had reduced motor outcomes at 2 years of age. Our findings add to a growing literature suggesting that short apneas and periodic breathing are not benign.
Lien vers le texte intégral (Open Access ou abonnement)
12. Hudry K, Chetcuti L, Tan DW, Clark A, Aulich A, Bent CA, Green CC, Smith J, Fordyce K, Ninomiya M, Saito A, Hakoshima S, Whitehouse AJO. Accuracy of a 2-minute eye-tracking assessment to differentiate young children with and without autism. Mol Autism;2025 (Jul 10);16(1):36.
BACKGROUND: Eye-tracking could expedite autism identification/diagnosis through standardisation and objectivity. We tested whether Gazefinder autism assessment, with Classification Algorithm derived from gaze fixation durations, would have good accuracy (area under the curve [AUC] ≥ 0.80) to differentiate 2-4-year-old autistic from non-autistic children. METHODS: Community sampling (March 2019-March 2021) of 2:00–4:11 year-olds included children recruited into a diagnosed Autism Group (‘cases’) and Non-Autism ‘Control’ Group (with likely undiagnosed autism minimised). We recruited well beyond minimum necessary sample size to ensure within-group heterogeneity and allow exploratory subgroup analysis. Alongside Gazefinder eye-tracking attempted with all recruited participants, we collected parent-report measures for all children, and clinical/behavioural measures with autistic children. RESULTS: 102 autistic (81.4% male; M(age)= 44mths; SD = 8.8) and 101 non-autistic children (57.4% male; M = 40; SD = 10.5) were recruited and eligible; the former slightly older, proportionately more male, and reflecting greater socio-demographic diversity. Gazefinder autism assessment was completed with 101 non-autistic children (n = 1 returning minimal data), and attempted with 100- and completed with 96 autistic children (n = 2 not attempted following adverse responses to clinical testing; n = 4 attempted but unable to calibrate). The Non-Autism Group returned significantly more overall tracking data. The final Classification Algorithm (range 0-100; threshold score = 28.6)—derived from n = 196 children’s fixation durations to elements of social/non-social scenes, human face presentations, and referential attention trials—had AUC = 0.82 (sensitivity = 0.82, specificity = 0.70). Compared to those correctly classified, autistic children misclassified as ‘controls’ showed greater overall tracking, and less pronounced autism features and developmental disability. Compared to correctly classified non-autistic children, those misclassified as ‘cases’ were older with lower overall tracking. LIMITATIONS: Our groups differed on socio-demographic characteristics and overall tracking (included within the Classification Algorithm). We used the ‘Scene 10A’ stimulus set as provided, without update/modification. Industry employees who developed the final Algorithm were non-blinded to child group, and considered only gaze fixation durations. Community sampling and ‘case-control’ design—comparing diagnosed autistic vs. non-autistic children—could be improved via future referral-based recruitment. CONCLUSIONS: Most children tolerated Gazefinder autism assessment, and our Classification Algorithm properties approached those reported from other Gazefinder use and established clinical assessments. Independent replication is required, and research informing the most suitable clinical application of this technology. TRIAL REGISTRATION: ACTRN12619000317190 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13229-025-00670-4.
Lien vers le texte intégral (Open Access ou abonnement)
13. Kagawa T, Yamaguchi Y, Kokubu Y, Sudo G, Ebisawa A, Hattori S, Takao K, Konno K, Nakagata N, Inoue T, Watanabe M, Inazawa J, Miyakawa T, Taga T. Mutation of the histone demethylase Gasc1 causes ASD-like symptoms in mice. Inflamm Regen;2025 (Jul 9);45(1):22.
BACKGROUND: Genomic analyses of psychiatric disorders, including autism spectrum disorder (ASD), have revealed many susceptibility genes, suggesting that such disorders may be caused by multiple factors. In this sense, it has long been a question whether there is an abnormal genetic status that comprehensively explains the pathogenesis of neuropsychiatric disorders or a »promising upstream treatment target »that normalizes symptoms. METHODS: To address this question, we provide important clues with respect to GASC1 (JMJD2 C/KDM4 C), which is a histone demethylase that prominently targets trimethylated histone H3 at lysine 9 (H3 K9 me3). Gasc1 hypomorphic mutant mice were analyzed using molecular biological, biochemical, behavioral battery tests, histological, and electrophysiological techniques. RESULTS: Mice homozygous for a hypomorphic mutation in Gasc1 exhibited abnormal behaviors, including hyperactivity, stereotyped behaviors, and impaired learning and memory, which are reminiscent of those of human psychiatric disorders. Electrophysiological studies of hippocampal slices revealed decreased paired-pulse facilitation and enhanced long-term potentiation, suggesting synaptic dysfunction in the mutants. Increased dendritic spine density in CA1 neurons was also detected in the mutants. Intriguingly, genetic linkage studies of human ASD have mapped a susceptibility locus on chromosome 9p24.1, which contains 78 genes, including the GASC1 gene. CONCLUSION: Taken together, our data suggest that histone demethylation plays a pivotal role in normal brain development and higher-order brain functions in both mice and humans.
Lien vers le texte intégral (Open Access ou abonnement)
14. Leahy C, Major S, Howard J, Carpenter KLH, Tenenbaum E, Franz L, Vermeer S, Grapel J, Compton S, Spanos M, Dawson G. Attentional and electrophysiological associations with executive function ability in young autistic children. Sci Rep;2025 (Jul 10);15(1):24883.
Difficulties in executive functioning (EF) have been consistently reported in autistic individuals, but less is known about the attentional and neural mechanisms driving these difficulties. We explored the associations between EF abilities and sustained attention, measured with eye-tracking, and spontaneous measures of EEG spectral power density in 176 2-8 year-old autistic children with a wide range of cognitive abilities. EF was measured using the Behavior Rating Inventory of Executive Function (BRIEF). We found that EF abilities were positively associated with look durations while watching complex, audiovisual stimuli involving social content and dyadic speech. We also found that EF was negatively associated with scalp-wide theta power and positively associated with frontal beta and gamma power. These results shed light on attentional and neural associations with EF abilities and underscore the role of frontal brain activity for EF in autism.
Lien vers le texte intégral (Open Access ou abonnement)
15. Leyhausen J, Gurr C, Berg LM, Seelemeyer H, Hermila B, Schäfer T, Chiocchetti AG, Pretzsch CM, Loth E, Oakley B, Buitelaar JK, Beckmann CF, Charman T, Bourgeron T, Barthome E, Banaschewski T, Jones EJ, Murphy D, Ecker C. Parsing Autism Heterogeneity: Transcriptomic Subgrouping of Imaging-Derived Phenotypes in Autism. Biol Psychiatry Cogn Neurosci Neuroimaging;2025 (Jul 10)
BACKGROUND: Neurodevelopmental conditions, such as autism, are highly heterogeneous both at the mechanistic and phenotypic level. Parsing heterogeneity is therefore vital for uncovering underlying processes that could inform the development of targeted, personalized support. The study aimed to parse heterogeneity in autism by identifying subgroups that converge at both phenotypic and molecular levels. METHODS: An imaging-transcriptomics approach was used to link neuroanatomical imaging-derived phenotypes in autism to whole-brain gene expression signatures provided by the Allen Human Brain Atlas. Neuroimaging and clinical data of N=359 autistic participants aged 6-30 years were provided by the EU-AIMS Longitudinal European Autism Project. Individuals were stratified using data-driven clustering techniques based on the correlation between brain phenotypes and transcriptomic profiles. The resulting subgroups were characterized on the clinical, neuroanatomical, and molecular level. RESULTS: We identified three subgroups of autistic individuals based on the correlation between imaging-derived phenotypes and transcriptomic profiles which showed different clinical phenotypes. The individuals with the strongest transcriptomic associations to imaging-derived phenotypes showed the lowest level of symptom severity. The genesets most characteristic for each subgroup were significantly enriched for genes previously implicated in autism etiology, including processes like synaptic transmission and neuronal communication, and mapped onto different gene ontology categories. CONCLUSION: Autistic individuals can be sub-grouped based on the transcriptomic signatures associated with their neuroanatomical fingerprints, revealing subgroups that show differences in clinical measures. The study presents an analytical framework for linking neurodevelopmental and clinical diversity in autism to underlying molecular mechanisms, thus highlighting the need for personalized support strategies.
Lien vers le texte intégral (Open Access ou abonnement)
16. Litman A, Sauerwald N, Green Snyder L, Foss-Feig J, Park CY, Hao Y, Dinstein I, Theesfeld CL, Troyanskaya OG. Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs. Nat Genet;2025 (Jul 9)
Unraveling the phenotypic and genetic complexity of autism is extremely challenging yet critical for understanding the biology, inheritance, trajectory and clinical manifestations of the many forms of the condition. Using a generative mixture modeling approach, we leverage broad phenotypic data from a large cohort with matched genetics to identify robust, clinically relevant classes of autism and their patterns of core, associated and co-occurring traits, which we further validate and replicate in an independent cohort. We demonstrate that phenotypic and clinical outcomes correspond to genetic and molecular programs of common, de novo and inherited variation and further characterize distinct pathways disrupted by the sets of mutations in each class. Remarkably, we discover that class-specific differences in the developmental timing of affected genes align with clinical outcome differences. These analyses demonstrate the phenotypic complexity of children with autism, identify genetic programs underlying their heterogeneity, and suggest specific biological dysregulation patterns and mechanistic hypotheses.
Lien vers le texte intégral (Open Access ou abonnement)
17. Lotito MCF, Pinto ACT, Alves LC, Barbosa MA, Ferreira DC, Portela MB, Pereira AF, Tavares-Silva CM, Pastura G, de Araújo Castro GFB. Autism Spectrum Disorder: Sleep Characteristics in Children and Adolescents, and Their Relationship with Probable Sleep Bruxism, Anxiety, and Cortisol and Melatonin Levels-A Cross-Sectional Study of Children in Brazil. J Autism Dev Disord;2025 (Jul 10)
The study described the sleep characteristics (SC) of children/adolescents with Autism Spectrum Disorder (ASD), and examined their association with medication use, support level, chronotype, probable sleep bruxism (PSB), anxiety, salivary levels of cortisol (SalC) and melatonin (SalM). Methods: Following anamnesis and dental examination, anxiety was assessed using the SCARED questionnaire. The SCs were determined by two age-appropriate questionnaires, and the percentage of negative SCs (%Neg) was recorded. Saliva samples were collected to measure SalC and SalM levels. The sample comprised 85 ASD patients aged 2-16 years, of whom 80%, 50.6% were classified as support level 2, 83.5% used medication, 84.7% had an afternoon chronotype, 72.9% presented PSB, and 48.2%, anxiety. The mean %Neg was significantly higher in patients using medication (49.29 ± 15.88; p = 0.03) and those requiring more support (level 1: 41.57 ± 14.45; level 2: 50.78 ± 15.54; level 3: 55.11 ± 23.44; p = 0.019). Patients with anxiety showed a higher %Neg (51.31 ± 16.33) than those without anxiety (43.65 ± 15.79). The mean SalC and SalM levels were 13.29 ± 13.39 and 299.91 ± 241.77, respectively.. In children aged 2-6 years, one rhythmicity SC and two separation-related SCs were associated with SalC (p < 0.05); lower SalM levels were found in patients who "slept alone" (p = 0.02). In older patients, "moving while sleeping" was associated with lower SalC (p = 0.05), and three additional SCs were linked to reduced SalM levels (p < 0.05). The presence of negative SCs in ASD patients was more common in those taking medication, requiring more support, and presenting anxiety. Furthermore, SalC and SalM levels were associated with specific SCs, especially among individuals aged (7-16).
Lien vers le texte intégral (Open Access ou abonnement)
18. Lourenço DM, Zavalko S, Duarte AL, Sá-Santos S, Mateus JM, Rodrigues RS, Miranda-Lourenço C, Mouro FM, Viais R, Sebastião AM, Solá S, Diógenes MJ, Xapelli S. Cannabidivarin mitigates motor and cognitive impairments in a female mouse model of Rett syndrome. Life Sci;2025 (Jul 7);378:123846.
Rett Syndrome (RTT, #312750 – OMIM) is a rare, progressive neurodevelopmental X-linked disorder, caused mostly by mutations in the gene for the methyl CpG binding protein 2 (MECP2). MECP2 is a transcriptional and epigenetic regulator that has been proposed to modulate neuronal development and adult neurogenesis, processes disrupted in both RTT patients and mouse models. Cannabidivarin (CBDV), a non-psychotropic cannabinoid, has recently been shown to promote adult neurogenesis through a mechanism mediated by transient receptor potential cation channel subfamily V member 1 (TRPV1). This study aimed to investigate the effects of chronic CBDV administration in a female RTT mouse model. Pre-symptomatic Mecp2(tm1.1Bird/J) female mice underwent a chronic CBDV treatment (3 mg/kg/day), followed by behavioral tests to assess potential therapeutic effects. While CBDV did not prevent deficits in locomotor activity, it mitigated motor coordination impairments in RTT mice. Furthermore, the novel object recognition test suggested that CBDV treatment contributed to the preservation of cognitive function in these animals. Moreover, CBDV administration induced genotype-dependent differences in neural stem cell proliferation, indicating a potential vulnerability in adult hippocampal neurogenesis in Mecp2-deficient contexts. Taken together, these findings provide new insights into the role of CBDV in RTT and support for future research, highlighting its potential as a repurposed therapeutic agent.
Lien vers le texte intégral (Open Access ou abonnement)
19. McGivern B, Holling T, Guillen Sacoto MJ, Gudbjartsson H, Abdelrazek IM, Alawi M, Bai Y, Bodamer O, Crunk A, Dameron AE, Dyer LM, Henderson LB, Irons M, Kutsche K, McGowan C, Monaghan KG, O’Connor K, Rashid A, Redlich OL, Reich A, Simotas C, Welner S, Wentzensen IM. Homozygous variants in EIF3K associated with neurodevelopmental delay, microcephaly, and growth retardation. HGG Adv;2025 (Jul 10);6(3):100438.
We report two rare homozygous variants, including a recurrent missense and intronic variant, in the EIF3K gene in four unrelated individuals with global developmental delay, microcephaly, proportionate short stature, dysmorphic craniofacial features, digit flexion deformities, and the cardiac anomaly, patent ductus arteriosus. Three individuals, who were all of Puerto Rican descent, were homozygous for the NM_013234.3:c.128A>G; p.(Asp43Gly) variant in EIF3K and homozygous for a missense variant in SYNE4 (NM_001039876.2:c.355C>T; p.(Arg119Trp)). SYNE4 is associated with autosomal recessive bilateral sensorineural hearing loss, which was also reported in these probands. Analysis of our dataset confirmed these EIF3K and SYNE4 variants were in linkage disequilibrium in affected individuals, suggesting a possible common ancestor and founder event. A fourth individual from Egypt harbored the homozygous intronic variant c.355-13A>G in EIF3K, which segregated with the phenotype in the family and led to aberrant splicing of EIF3K pre-mRNAs, as shown by insertion of 12 intronic base pairs, skipping of 2 exons, and significantly reduced EIF3K protein levels in skin fibroblasts. Through genetic and functional approaches, we suggest that biallelic EIF3K variants are associated with an autosomal recessive syndromic neurodevelopmental disorder with growth retardation, microcephaly, congenital heart defect, and other anomalies.
Lien vers le texte intégral (Open Access ou abonnement)
20. Moreira RS, Guimarães MAP, Magalhães LC, Moreira JM, Alves CRL. Early symptoms of autism spectrum disorders and association with Brazilian children’s development and behavior. Codas;2025;37(4):e20240306.
PURPOSE: to examine the association between the early autism spectrum disorder (ASD) signs and developmental and behavioral performance of Brazilian children aged 18 to 34 months. METHODS: A cross-sectional study with 221 children recruited at public healthcare and early education services. Early symptoms of ASD were screened using the Parental Observations of Social Interaction (POSI). Children’s development and behavior were examined using the Ages and Stages Questionnaires (ASQ-3) and Survey of Well-being of Young Children (SWYC-BR). The results of children at risk for ASD were compared to the no-risk ones using Chi-square and t-test. RESULTS: The overall frequency of children at risk for ASD (POSI-positive screening) was 33% and did not differ across children’s age range and gender. Children at risk for ASD showed worse socio-emotional behaviors (p=0.004) and lower scores for overall development (p=0.0001), communication (p=0.0007), fine motor (p=0.04), and personal-social domains (p=0.01). Differences between groups varied according to children’s age and across developmental/behavioral domains and were more evident in older children. Children aged 30 to 34 months presented significant differences in overall development (p=0.001), behavior (p=0.004), and the personal-social domains (p=0.03). CONCLUSIONS: The frequency of children at risk for ASD was higher than described in the literature. Also, the development and behavior of children at risk for ASD were significantly different from their peers and compatible with the presentation of ASD in young children. Our findings reinforce the need for systematic and holistic surveillance of child development during well-being visits to improve ASD early detection.
Lien vers le texte intégral (Open Access ou abonnement)
21. Nafisah I, Mahmoud N, Ewees AA, Khattap MG, Dahou A, Alghamdi SM, Fares IA, Azmi Al-Betar M, Abd Elaziz M. Deep learning-based feature selection for detection of autism spectrum disorder. Front Artif Intell;2025;8:1594372.
INTRODUCTION: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by challenges in communication, social interactions, and repetitive behaviors. The heterogeneity of symptoms across individuals complicates diagnosis. Neuroimaging techniques, particularly resting-state functional MRI (rs-fMRI), have shown potential for identifying neural signatures of ASD, though challenges such as high dimensionality, noise, and small sample sizes hinder their clinical application. METHODS: This study proposes a novel approach for ASD detection utilizing deep learning and advanced feature selection techniques. A hybrid model combining Stacked Sparse Denoising Autoencoder (SSDAE) and Multi-Layer Perceptron (MLP) is employed to extract relevant features from rs-fMRI data in the ABIDE I dataset, which was preprocessed using the CPAC pipeline. Feature selection is enhanced through an optimized Hiking Optimization Algorithm (HOA) that integrates DynamicOpposites Learning (DOL) and Double Attractors to improve convergence toward the optimal subset of features. RESULTS: The proposed model is evaluated using multiple ASD datasets. The performance metrics include an average accuracy of 0.735, sensitivity of 0.765, and specificity of 0.752, surpassing the results of existing state-of-the-art methods. DISCUSSION: The findings demonstrate the effectiveness of the hybrid deep learning approach for ASD detection. The enhanced feature selection process, coupled with the hybrid model, addresses limitations in current neuroimaging analyses and offers a promising direction for more accurate and clinically applicable ASD detection models.
Lien vers le texte intégral (Open Access ou abonnement)
22. Ordin M, Barbarroja N, Polyanskaya L, Manrique HM, Castelo-Branco M. Metacognition and Cognitive Flexibility in Autistic and Neurotypically-Developing Populations. Brain Behav;2025 (Jul);15(7):e70668.
PURPOSE: Whether and how metacognition is altered in individuals with autistic spectrum disorder (ASD) is intensely debated. Metacognitive deficit is claimed to be related to cognitive inflexibility, accounting for restrictive behaviors in ASD individuals. We wanted to test this hypothesis by measuring metacognition in ASD and in matched neurotypically developing (TD) control samples in a task that relies on visuo-spatial cognition, in which ASD allegedly have an advantage. METHODS: We measured metacognition in a 3D mental rotation task. Additionally, we administered a trading game: players had to figure out the rules for maximizing the profit on each transaction. These rules changed in the middle of the game, which required that players modify their strategy to keep the profit at maximum. We measured both learning efficiency (how fast players extract the rules) and re-learning speed (cognitive flexibility, how fast learners could adjust their behavioral responses after rules are changed). RESULTS: TD outperform ASD individuals in terms of accuracy in mental rotation but exhibited lower metacognitive efficiency (i.e., were less aware when they were more likely to make an error). No differences in learning efficiency and cognitive flexibility between TD and ASD individuals were observed. Neither did we observe an association between cognitive flexibility and metacognition. Nevertheless, both in ASD and TD populations, overconfidence in one’s decisions is negatively correlated with cognitive flexibility, but not with learning efficiency. CONCLUSION: ASD individuals can have superior metacognition in tasks that rely on visuo-spatial cognition. Cognitive flexibility is diminished by overconfidence, not by metacognitive deficit.
Lien vers le texte intégral (Open Access ou abonnement)
23. Pope L, Light J, Exton K. Incorporating Visual Scene Display Augmentative and Alternative Communication Supports Into Naturalistic Developmental Behavioral Interventions. Am J Speech Lang Pathol;2025 (Jul 10);34(4):2260-2279.
PURPOSE: Naturalistic developmental behavioral interventions (NDBIs) are a promising approach for supporting early language and communication development for young children on the autism spectrum.(1) However, the children with the greatest need of language supports-those with minimal speech-have limited means to participate within these interventions and are therefore the least likely to benefit from traditional NDBIs that focus primarily on speech production. METHOD: Using a single-case, multiple-probe across participants design, the current study investigated whether adding visual scene display (VSD) augmentative and alternative communication (AAC) supports with just-in-time programming and aided AAC input to NDBI procedures within an interactive storybook reading context resulted in (a) an increase in the number of symbolic communicative turns or (b) an increase in the rate of the number of different unique concepts expressed by young children on the autism spectrum with minimal speech. RESULTS: All participants tended to take more symbolic communicative turns each session and add new expressive vocabulary more rapidly with the addition of VSD AAC supports as compared to NDBI procedures alone, although with notable variation across participants. CONCLUSIONS: The results of this study indicate that including VSD-based aided AAC systems and strategies designed to support beginning communicators within the framework of an NDBI can increase both the communication frequency and expressive vocabulary of children on the autism spectrum with minimal speech, beyond the effects of NDBI procedures alone. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.29374061.
Lien vers le texte intégral (Open Access ou abonnement)
24. Posar A, Visconti P. The Work of Grunya Efimovna Sukhareva in the Field of Autism Spectrum Disorder One Hundred Years After Her Original Description. Turk Arch Pediatr;2025 (Jul 1);60(4):434-437.
Despite several articles that in recent years have highlighted the work of the Russian child psychiatrist and researcher Grunya Efimovna Sukhareva (Kiev, 1891 – Moscow, 1981), even today the prevailing opinion, at least in the Western world, does not attribute to this author the merit of the original clinical description of autism spectrum disorder. In fact, this credit is still attributed today first to Leo Kanner and second to Hans Asperger, who in 1943 and 1944 respectively described some cases of children who today would certainly be diagnosed with autism spectrum disorder. In reality, almost 20 years earlier than Kanner and Asperger, that is in 1925, Sukhareva published a paper in which she described with great accuracy and in a modern way the cases of 6 children affected, using current terminology, by autism spectrum disorder, that today would be defined as « high-functioning. » Later, in 1927, Sukhareva described 5 girls affected, emphasizing the sex-related differences in autistic features, which today represent a very current and still debated topic. Over the next few decades, her work remained largely unknown to most of the Western scientific world. In this paper, the intention is to pay tribute to Sukhareva’s work in particular (but not only) in the field of autism and discuss some possible hypotheses as to why it has been ignored by most for decades.
Lien vers le texte intégral (Open Access ou abonnement)
25. Salehi AM, Chegini SB, Esmaeili F, Rabiei N, Jenabi E, Rezaei M. The Psychometric Properties of the Iranian Version of Repetitive Behavior Scale-Revised (RBS-R) Questionnaire in Children With Autism Spectrum Disorder. Health Sci Rep;2025 (Jul);8(7):e70984.
BACKGROUND AND AIMS: Restricted and repetitive behaviors (RRBs) are fundamental characteristics of autism spectrum disorders (ASD). There is a need for a reliable and valid instrument to evaluate the diversity of RRBs and assess their severity. The Repetitive Behavior Scale-Revised (RBS-R) is a recognized tool for screening RRBs. This study aims to investigate the psychometric properties of the RBS-R questionnaire in Iran by identifying children with ASD who have Persian-speaking parents. METHODS: In this case-control study conducted in 2024 in Hamadan, 160 children were included: A case group diagnosed with autism (25 girls, 52 boys) and a control group of healthy volunteer children (30 girls, 53 boys) aged 4-12 years. The ASD group exhibited a minimum mean length of utterance (MLU) of 2. Participants diagnosed with intellectual disabilities were excluded from the study. The study assessed the reliability, content validity, and face validity to evaluate the psychometric properties of the tool. Exploratory factor analysis was used to identify questionnaire subscales. All assumptions, including the Kaiser-Meyer-Olkin (KMO) test, Bartlett’s test, and question correlations, were checked. Subscales were extracted using ordinary least squares (OLS) and Equamax rotation, with the number of subscales determined based on the Scree plot method and eigenvalues greater than 1. RESULTS: The study identified six factors (aggressive, focused and self-harming, resistant to change, obsessive, ritualistic, and insistent), which together explained 51.082% of the total variance. The Cronbach’s alpha value for the Persian version of RBS-R was reported as 0.924. The questionnaire showed a sensitivity of 88.31%, specificity of 83.13%, positive predictive value of 82.93%, negative predictive value of 88.46%, and an area under the curve of 91.7%. The selected cutoff value in this study was determined to be 17.5. CONCLUSION: The Persian version of the RBS-R is valid and reliable. It also demonstrated acceptable internal consistency and sensitivity, suggesting that it can be used as a screening measure for ASD in Iran.
Lien vers le texte intégral (Open Access ou abonnement)
26. Santos J. Expanding the neurodevelopmental relevance of the SC-VTA pathway in autism spectrum disorder. Mol Psychiatry;2025 (Jul 10)
Lien vers le texte intégral (Open Access ou abonnement)
27. Scheeren AM, Nieuwenhuis S, Crane L, Roke Y, Begeer S. Masking, social context and perceived stress in autistic adults: An ecological momentary assessment study. Autism;2025 (Jul 9):13623613251353358.
Masking may entail the suppression of autistic traits by autistic individuals. Thus far, research indicates a negative impact of autistic masking on mental health, but this is largely based on retrospective surveys. In this study, we used ecological momentary assessment to examine real-time associations between social context (i.e. presence of (non-)autistic others), masking, and perceived stress in everyday life among a sample of autistic adults. Ecological momentary assessment data were collected via a smartphone application for 87 autistic individuals (58 females; M age = 48; age range: 17-68). In line with the hypotheses, repeated measures analyses of variance and linear mixed models indicated that (1) participants reported masking significantly less when they were alone compared with when others were present, (2) participants masked significantly more when non-autistic others were present compared with autistic others, and (3) more masking was associated with a concurrent higher level of perceived stress. Autistic adults reported they could be more themselves among autistic peers and reduced masking was associated with reduced stress. These ecological momentary assessment study findings provide ecological validity to the potential stressful impact of masking in the daily lives of autistic adults.Lay abstractAutistic people may try to hide their autistic traits in order to fit in. This is called autistic masking. Survey research suggests that autistic masking may have a negative effect on the mental well-being of autistic people. Yet, survey research has limitations, because people may not remember or may not accurately report how much they masked and how they felt in the past. Therefore, in this study, we asked autistic adults to use a smartphone app to report with whom they were (with or without autistic people), if they could be themselves (degree of masking), and how stressed they felt during the past 4 h. Participants reported this information multiple times over a period of 28 days. In total, 87 autistic adults participated (58 females; age range: 17-68). In line with our expectations, (1) participants masked less when they were alone compared with when others were present, (2) participants masked more when non-autistic others were present compared with autistic others, and (3) more masking was linked with the experience of more stress in the same moment. Autistic adults reported they could be more themselves among other autistic individuals. Also, less masking was associated with less stress. Our study shows the everyday reality of stress during masking experienced by autistic adults.
Lien vers le texte intégral (Open Access ou abonnement)
28. Skommer J, Gunesh K. Autism, menstruation and mental health- a scoping review and a call to action. Front Glob Womens Health;2025;6:1531934.
INTRODUCTION: There is increasing evidence regarding the mental health implications of cyclical hormonal fluctuations associated with menstruation, as well as of key reproductive transitions (menarche and menopause), in typically developing individuals. Autism spectrum disorder (ASD), a complex neurodevelopmental condition, may predispose individuals to maladaptive responses to life changes such as menstruation. Despite the importance of this topic, research relating to menstrual experiences across the lifespan of autistic adults remains scarce, largely due to the intersecting effects of multiple marginalizing characteristics experienced by this population. This research gap significantly limits our understanding of how menstruation impacts the mental health of autistic individuals. OBJECTIVES: The purpose of this scoping review was to examine existing evidence about menstrual experiences, including menarche and menopause, and their impact on mental health among autistic individuals, and propose a biopsychosocial framework for the complex interplay of individual, healthcare, and societal vulnerabilities that predispose autistic individuals to negative menstrual experiences. METHODS: A scoping review of original articles, quantitative and qualitative, published in English from 1980 onwards, identified through search of online databases and reference lists, using PRISMA extension for scoping reviews. RESULTS: A total of 45 studies were identified to meet the specified inclusion and exclusion criteria. The key emerging themes were the mental health impact of menstruation, the occurrence and experience of menstrual disorders among autistic individuals, as well as support strategies and healthcare utilization by that population. CONCLUSIONS: Although our current knowledge on menstrual health specific to autistic individuals is still scant, it nevertheless raises significant concerns regarding potential challenges. The findings of this study have been placed within the bio-psycho-socio-cultural framework to emphasize that menstrual experiences occur within the context of person-environment transactions, and that autistic individuals are vulnerable to negative menstrual experiences because of adverse or non-facilitative societal and healthcare environments. Further large-scale studies addressing identified gaps (e.g., influence of gender diversity, impact of medical comorbidities, trauma and stigma) is warranted. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/gxurq.
Lien vers le texte intégral (Open Access ou abonnement)
29. Uscătescu LC, Hyatt CJ, Dunn J, Kronbichler M, Calhoun V, Corbera S, Pelphrey K, Pittman B, Pearlson G, Assaf M. Using the excitation/inhibition ratio to optimize the classification of autism and schizophrenia. Transl Psychiatry;2025 (Jul 9);15(1):234.
The excitation/inhibition (E/I) ratio has been shown to be imbalanced in individuals diagnosed with autism (AT) or schizophrenia (SZ), relative to neurotypically developed controls (TD). However, the degree of E/I imbalance overlap between SZ and AT has not been extensively compared. In this project, we used resting state fMRI data to estimate the E/I ratio via the Hurst (H) exponent. Our main objectives were (1) to quantify group differences in the E/I ratio between TD, AT, and SZ, (2) to assess the potential of the E/I ratio for differential diagnosis, and (3) to verify the replicability of our findings in an independently acquired dataset. For each participant, we computed the Hurst exponent (H), an indicator of the E/I ratio, from the time courses of 53 independent components. Using a random forest classifier (RF), we ran a classification analysis using the larger of the two datasets (exploratory dataset; 519 TD, 200 AT, 355 SZ) to determine which of the 53 H would yield the highest performance in classifying SZ and AT. Next, taking the ten most important H based on the exploratory dataset, in combination with phenotypic information collected in the replication dataset (55 TD, 30 AT, 39 SZ), we used RF to compare the classification performance using five feature sets: (a) H only; (b) Positive and Negative Syndrome Scale (PANSS) and the Autism Diagnostic Observation Schedule (ADOS) only; (c) PANSS, ADOS, Bermond-Vorst Alexithymia Questionnaire (BVAQ), Empathy Quotient (EQ), and IQ; (d) H, PANSS and ADOS; (e) H, PANSS, ADOS, BVAQ, EQ and IQ. Classification performance using H only was higher in the exploratory dataset (AUC = 84%) compared to the replication dataset (AUC = 72%). In the replication dataset, the highest classification performance was obtained when combining H with PANSS, ADOS, BVAQ, EQ and IQ (i.e., model e; AUC = 83%). These results illustrate the added value of E/I to typical phenotypic data in differentiating AT and SZ.
Lien vers le texte intégral (Open Access ou abonnement)
30. Yang J, Zhang R. Melodic bridges: music intervention as a catalyst for social skills development in preschool children with autism. Front Psychol;2025;16:1542662.
Autism spectrum disorder (ASD) is characterized by persistent challenges in social communication, emotional regulation, and cooperative behavior. While traditional behavioral therapies are widely used, they can lack engagement and flexibility. Music interventions, by engaging multiple neural and emotional systems, offer a promising alternative to address these core deficits. This randomized controlled trial (RCT) evaluated the efficacy of a 12-week structured music intervention in improving social skills in preschool children with ASD. Sixty participants (aged 3-6 years) were randomly assigned to an experimental group (music intervention) or a control group (behavioral therapy). Therapeutic music activities included rhythm training, interactive singing, instrumental improvisation, and group games, conducted three times weekly. Social skills were assessed using the Social Responsiveness Scale (SRS) and observational data at baseline (T0), mid-intervention (T1), post-intervention (T2), and six-week follow-up (T3). The music intervention demonstrated significant improvements in social communication, emotional regulation, and social motivation compared to the control group. Interactive singing showed the strongest impact on social communication, fostering verbal reciprocity and turn-taking. Rhythm training enhanced social motivation and joint attention, while instrumental improvisation improved emotional regulation by providing a non-verbal outlet for self-expression. Group games facilitated peer interaction and cooperation. These improvements were sustained at T3, underscoring the intervention’s durability. This study highlights the transformative potential of music interventions in addressing core social deficits in preschool children with ASD. By leveraging rhythm, melody, and improvisation, music therapy offers a scalable, engaging, and effective therapeutic approach. These findings support the integration of music-based interventions into early education and clinical settings, paving the way for more personalized and inclusive therapies for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
31. Zarate-Lopez D, García-Carrillo R, Castro-Sánchez L, Galvez-Contreras AY, Gonzalez-Perez O. Spironolactone Partially Reverses Autism-Like Behaviors Linked to ErbB4 and mTOR Phosphorylation in the Mouse Prefrontal Cortex and Striatum. Arch Med Res;2025 (Jul 10);56(7):103254.
BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a condition resulting from a combination of genetic and environmental influences that lead to atypical brain development, particularly in regions such as the striatum and prefrontal cortex. There is increasing evidence linking the epidermal growth factor (EGF) and its receptor (EGFR or ErbB1) to the etiopathogenesis of ASD. However, ErbB4, another ErbB member, has also been implicated in this process. To investigate whether dysregulation of ErbB4 and its downstream mTOR signaling pathway in the striatum and prefrontal cortex contributes to stereotypical behaviors and social deficits in an autism-like rodent model. METHODS: We analyzed the phosphorylation levels of ErbB4and mTOR in the prefrontal cortex and striatum of 31 d old mice that were prenatally exposed to valproate (VPA; 500 mg/kg) or the control vehicle (0.9 % NaCl). Social and stereotypic behaviors were assessed using the three-chamber social test and the marble burying test, respectively. Then, the VPA groups were treated with 50 mg/kg of spironolactone, a selective ErbB4 antagonist. RESULTS: Prenatal exposure to VPA induced deficits in social interaction and an increase in repetitive behaviors. These behaviors coexist with dysregulation of the ErbB4 phosphorylation and modifications in the mTOR signaling pathway in both brain regions. Treatment with spironolactone reduced repetitive behaviors, which was consistent with reduced ErbB4 phosphorylation and mTOR signaling. CONCLUSIONS: These results support the idea that ErbB4 has abnormal expression and activity levels in the striatum and prefrontal cortex. Antagonizing ErbB4 with spironolactone improves repetitive behavioral patterns associated with ASD.