1. Ahirwar LK, Blackburn SL, McBride DW, T PK. Reviewing vascular influences on neuronal migration, cortical development, and neurodevelopmental disorders: focus on autism, ADHD and schizophrenia. Mol Psychiatry;2025 (Sep 2)

During cortical development, newly born neurons migrate radially or tangentially from their origin to expand the cortex. Simultaneously, neuron-derived factors support angiogenesis, and an elaborate network of blood cerebral vessels develops in the cortex. Traditionally, blood cerebral vessels were considered to support the growing cortex or migrating neurons by providing nutrients and oxygen. However, recent studies have shed light on Endothelial cells’ influence on cortical development; they guide neuronal migration by providing molecular cues and structural support. Here, we review the current understanding of how CNS cerebral vessels support neurogenesis, neuronal migration, and the formation of the six-layer cortical structure during development. Additionally, we explore current knowledge regarding the vascular role in neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, and schizophrenia.

Lien vers le texte intégral (Open Access ou abonnement)

2. Almuqhim F, Saeed F. Overcoming Site Variability in Multisite fMRI Studies: an Autoencoder Framework for Enhanced Generalizability of Machine Learning Models. Neuroinformatics;2025 (Sep 2);23(3):46.

Harmonizing multisite functional magnetic resonance imaging (fMRI) data is crucial for eliminating site-specific variability that hinders the generalizability of machine learning models. Traditional harmonization techniques, such as ComBat, depend on additive and multiplicative factors, and may struggle to capture the non-linear interactions between scanner hardware, acquisition protocols, and signal variations between different imaging sites. In addition, these statistical techniques require data from all the sites during their model training which may have the unintended consequence of data leakage for ML models trained using this harmonized data. The ML models trained using this harmonized data may result in low reliability and reproducibility when tested on unseen data sets, limiting their applicability for general clinical usage. In this study, we propose Autoencoders (AEs) as an alternative for harmonizing multisite fMRI data. Our designed and developed framework leverages the non-linear representation learning capabilities of AEs to reduce site-specific effects while preserving biologically meaningful features. Our evaluation using Autism Brain Imaging Data Exchange I (ABIDE-I) dataset, containing 1,035 subjects collected from 17 centers demonstrates statistically significant improvements in leave-one-site-out (LOSO) cross-validation evaluations. All AE variants (AE, SAE, TAE, and DAE) significantly outperformed the baseline mode (p < 0.01), with mean accuracy improvements ranging from 3.41% to 5.04%. Our findings demonstrate the potential of AEs to harmonize multisite neuroimaging data effectively enabling robust downstream analyses across various neuroscience applications while reducing data-leakage, and preservation of neurobiological features. Our open-source code is made available at https://github.com/pcdslab/Autoencoder-fMRI-Harmonization .

Lien vers le texte intégral (Open Access ou abonnement)

3. Anderson JS, Silverman JL, Lodigiani AL, Barbaduomo CM, Beegle JR. Transduction of hematopoietic stem and progenitor cells by an MECP2 lentiviral vector improves Rett syndrome phenotypes. Front Drug Discov (Lausanne);2025;5

INTRODUCTION: Rett Syndrome is a genetic neurodevelopmental disorder caused by decreased levels of MeCP2. Due to mutations in the MECP2 gene, insufficient MeCP2 protein levels lead to clinical phenotypes including the loss of normal movement, decreased communication, seizures, sleep disorders, and breathing problems. Currently there is no cure for Rett Syndrome and the only means to help patients is palliative care directed to their specific symptoms. Therefore, novel therapies need to be developed to alleviate disease phenotypes by restoring normal MECP2 expression. An autologous hematopoietic stem cell and gene therapy approach for Rett syndrome may offer a benefit to affected patients by systemic delivery of functional MeCP2, including to affected neurons in the central nervous system. METHODS: In our current experiments, we evaluated the therapeutic effect of MECP2 lentiviral vector transduced human CD34+ hematopoietic stem and progenitor cells after transplantation into an immunodeficient mouse model of Rett syndrome. RESULTS: We observed improvement of Rett syndrome-related phenotypes including the reversion toward normal motor abilities in an open field assay for total activity, horizontal activity, and vertical rearing activity, and an increased latency to fall in a rotarod assay. An increased level of MeCP2 protein was also observed in the brain tissue of transplanted mice. DISCUSSION: By providing functional MeCP2 to affected cells, our results highlight the ability of this strategy to improve Rett syndrome phenotypes. These proof-of-concept studies demonstrate the potential use of a stem cell gene therapy approach as a novel treatment for Rett syndrome patients.

Lien vers le texte intégral (Open Access ou abonnement)

4. Boeri S, Piai M, Russo S, Alari V, Cogliati F, Simonetta D, Benke TA, Nobili L, Prato G. Clinical differences in monozygotic twins with Rett syndrome: case report and systematic review. Orphanet J Rare Dis;2025 (Sep 2);20(1):473.

BACKGROUND: Rett Syndrome (RTT) is a rare, and severe neurodevelopmental disorder that primarily affects females and is primarily (> 96%) due to pathogenic loss-of-function genetic variants of methyl-CpG-binding protein 2 (MECP2). Despite the rarity of the syndrome, sporadic twin cases have been reported. The descriptions have often focused on the phenotype, emphasizing differences or similarities. We report the case of monozygotic (MZ) twins with RTT carrying the same MECP2 mutation and perform a systematic review of the cases of MZ twins. METHOD: We searched PubMed and Embase for articles reporting MZ twins with RTT who met Neul criteria and carried mutations in the MECP2 gene. We focused on phenotypic discordance and X chromosome inactivation (XCI). RESULTS: Our search yielded 115 results, 18 of which were included in our systematic review. We identified 17 pairs of twins, with 11 showing a discordant phenotype. Data on XCI were reported for only six pairs. We describe MZ twins with typical RTT syndrome who shared the same p.Thr158Met pathogenic variant on the MECP2 gene but exhibited different severity of clinical phenotype, especially regarding epilepsy. The XCI pattern and expression of the wild-type allele in blood were similar in both twins, suggesting that XCI differences assessed in blood may not account for the phenotypic variability. Mononucleate cells were isolated from both twins to generate induced pluripotent stem cells (iPSCs). The patient with more mutated clones presented a more severe phenotype. DISCUSSION: Cases of MZ twins with RTT are few, and the phenotypic difference described in our case and presented in the literature does not seem to be explained by different XCI patterns. Therefore, more detailed genetic investigations are necessary.

Lien vers le texte intégral (Open Access ou abonnement)

5. Castro K, Riesgo R, Gadia C. Autism spectrum disorder: overdiagnosis or are we facing a new pandemic?. J Pediatr (Rio J);2025 (Aug 30):101439.

OBJECTIVE: To critically analyze the factors influencing prevalence estimates of Autism Spectrum Disorder (ASD), considering methodological, clinical, etiological, and sociocultural determinants that shape epidemiological data and diagnostic practices. DATA SYNTHESIS: In recent decades, a substantial increase in ASD prevalence has been observed globally. This phenomenon is shaped by a combination of factors, including changes in diagnostic criteria, improved detection methods, expanded access to health services, and greater public awareness. However, it also raises concerns about possible overdiagnosis, particularly in complex clinical contexts. The interpretation of prevalence data is influenced by methodological designs, population characteristics, and sociocultural dynamics. SUMMARY OF THE FINDINGS: The absence of biological markers, the high rate of psychiatric comorbidities, and disparities in access to qualified professionals further complicate the diagnostic process. These elements highlight the need for caution when comparing data across studies, time periods, or geographic regions. CONCLUSION: The ASD prevalence reflects a multifaceted process that demands careful and comprehensive interpretation. A deeper understanding of this scenario requires critical reflection on how diagnoses are established, interpreted, and applied. Strengthening diagnostic practices and epidemiological approaches is essential to ensure more accurate data and support informed decision-making in health policies.

Lien vers le texte intégral (Open Access ou abonnement)

6. Cheong Y, Bae J, Lee S, Ro J, Okazawa H, Kosaka H, Jung M. Dissecting the heterogeneity of autism spectrum disorder with sensory behavior, brain, and epigenetic factors. Transl Psychiatry;2025 (Sep 1);15(1):337.

Autism spectrum disorder (ASD), a disorder with heterogeneous etiology, is characterized by abnormal behavioral responses to sensory inputs. However, there is still limited understanding of how brain and epigenetic factors, along with behavioral abnormality, contribute to ASD. After completing Adolescent-Adult Sensory Profile, a self-report questinnaire, 34 individuals with ASD and 72 controls underwent neuroimaging scans to measure brain structural (cortical and subcortical volume) and functional (thalamo-cortical resting-state functional connectivity) characteristics. For epigenetic measures, we computed DNA methylation values of the oxytocin receptor and arginine vasopressin receptor (AVPR) genes from the participants’ saliva. When sensory-related behavior was the default baseline, a machine learning algorithm demonstrated that the neuroimaging-epigenetic model outperformed the neuroimaging model or the epigenetic model. Thalamo-cortical hyperconnectivity and AVPR 1A epigenetic modification were found to be significant contributing factors in these models. By integrating neuroimaging and epigenetic biomarkers with behaviors, a more precise diagnosis of ASD can be achieved.

Lien vers le texte intégral (Open Access ou abonnement)

7. Christensen D, Shin YS, Wang J, Cuomo CR, Dentry T, Gemmell HM, Pulver SL, Orlando AM, McKinney WS, Stevens CJ, Unruh KE, Karmakar B, Coombes SA, Mosconi MW, Wang Z. Subcortical brain volume variations in autistic individuals across the lifespan. Mol Autism;2025 (Sep 1);16(1):46.

BACKGROUND: Structural alterations in subcortical brain regions-including the amygdala, hippocampus, basal ganglia, and cerebral ventricles-have been linked to various clinical features of autism spectrum disorder (ASD). However, volumetric features among these regions in autistic individuals across the lifespan remain poorly understood. This cross-sectional study aimed to investigate age-associated volumetric deviations in these clinically implicated subcortical regions of autistic individuals and neurotypical controls, and to examine the structural interrelationships within each group. METHODS: We examined multi-site T1-weighted MRI data from 119 autistic and 122 neurotypical participants aged 7-73 years. Volumetric data for the amygdala, hippocampus, basal ganglia, and cerebral ventricles were harmonized across sites using the ComBat algorithm. Following this, volumetric composite indices (principal component scores) were extracted for each region using principal component analysis. These scores represent dominant volumetric patterns of each subcortical region, with higher values reflecting greater volume. These composite scores were then compared between groups and with increasing age. RESULTS: Autistic participants exhibited greater amygdala volume in early life, followed by more pronounced age-associated reductions in adulthood compared to neurotypical controls. A similar trend was observed for the hippocampus, with early volumetric enlargement giving way to steeper declines in later years. In contrast, the autistic group consistently trended towards larger basal ganglia across the lifespan. Additionally, autistic participants showed accelerated enlargement in the cerebral ventricles with increasing age. Both groups exhibited patterns of inverse volumetric associations between the cerebral ventricles and surrounding subcortical regions in later adulthood; however, these relationships were more pronounced and widely distributed in the autistic group. LIMITATIONS: The cross-sectional design of this study limited us from capturing intra-individual differences at baseline and quantifying the lifespan trajectories of each participant. Site-related sampling differences may have introduced cohort bias in the results. CONCLUSIONS: Autistic participants and neurotypical controls exhibit distinct, age-related volumetric patterns across key subcortical brain regions. Enlargement of the cerebral ventricles and their inverse structural relationships with neighboring structures in later life may indicate atrophic processes beginning in middle adulthood in ASD. These findings highlight the need to further investigate mechanisms of atypical brain aging in ASD and consider these subcortical brain regions as potential biomarkers of neurodegeneration and intervention targets across the adult lifespan.

Lien vers le texte intégral (Open Access ou abonnement)

8. Eley SEA, Weissgold S, Stanfield AC. Preliminary perspectives on gene therapy in fragile X syndrome: a caregiver view. J Neurodev Disord;2025 (Sep 1);17(1):55.

BACKGROUND: There have been increasing numbers of clinical trials of medications for fragile X syndrome (FXS) in recent years, many targeted at proposed underlying cellular or circuit based mechanisms. As yet none of these have led to widespread changes in clinical practice. Genetic therapies represent a different therapeutic approach, which aim to address the genetic mechanisms by which FXS arises. Although not yet moving into human studies in FXS, this is an area of increasing research importance in neurodevelopmental conditions more broadly. It is important that families affected by FXS get the chance to give their views about future genetic therapies, given the potential controversies around genetic therapies. METHODS: We developed a questionnaire to capture caregiver views around gene therapy in FXS. The questionnaire was developed alongside a group of parents / caregivers of a child with FXS to ensure the language used was appropriate and that it would allow a variety of views to be captured. The questionnaire contained questions around current knowledge of gene therapy, what families think of gene therapy and their views on gene therapy trials taking place. Responses were analysed by thematic analysis carried out by two of the authors with data from the questionnaires being grouped into themes and subthemes. RESULTS: The questionnaire was completed by 195 individuals who are parents of, or who care for, someone with FXS. Respondents were primarily from the UK (60.5%) and the Americas (22.1%). The majority of dependants were male (86%). Responses showed a strong interest from the Fragile X community in gene therapy trials taking place, with themes emerging around quality of life, outcomes and feelings. Hope for positive change was balanced against caution about unintended consequences, the newness of the treatment and tolerability. CONCLUSION: Overall, caregivers felt hopeful, excited and interested in the prospect of gene therapy potentially providing a new treatment option, but there was some trepidation about the potential effects. Taking caregiver views into account will help inform decisions around the development and testing of any future genetic interventions.

Lien vers le texte intégral (Open Access ou abonnement)

9. Elmquist M, Crowe B, Wattanawongwan S, Reichle J, Pierson L, Simacek J, Hong ER, Liao CY, Ganz JB. Caregiver-Implemented AAC Interventions for Children with Intellectual or Developmental Disabilities: a Systematic Review. Rev J Autism Dev Disord;2025 (Jun);12(2):290-310.

Many children with intellectual and/or developmental disabilities benefit from augmentative and alternative communication strategies (AAC) to increase their communicative competency. Furthermore, caregiver-implemented AAC interventions are an effective and efficient strategy to improve communication outcomes. We reviewed the caregiver-implemented AAC intervention literature to assess child and caregiver characteristics, what kind of interventions caregivers were taught, how caregivers were trained, and how studies evaluated caregiver implementation. We found that families from marginalized backgrounds were underrepresented. Most studies used functional behavioral interventions and various teaching strategies, and few included caregiver-dependent variables. We discuss our results in the context of improving future caregiver-implemented AAC interventions and, in turn, child communication outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

10. Galeh TM, Nayeri T, Dodangeh S, Hosseininejad Z, Tanzif A, Khalilian A, Daryani A. Possible association between Toxoplasma gondii infection and autism spectrum disorder. Parasites Hosts Dis;2025 (Aug);63(3):201-214.

Toxoplasma gondii is a neurotropic apicomplexan protozoan estimated to affect approximately 30% of the global population. In this review, we aimed to examine scientific evidence on the potential role of T. gondii infection in the development of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder. This review summarizes the current literature exploring the possible association between T. gondii and ASD. Findings indicate that toxoplasmosis may contribute to host alterations, including the induction of humoral and cellular immune responses, production of various cytokines, and changes in neurotransmitter levels (e.g., serotonin, dopamine, acetylcholine, gamma-aminobutyric acid, and glutamate), as well as the activation of enzymes such as indoleamine 2,3-dioxygenase, which may influence the pathophysiology of ASD. In conclusion, this review suggests that T. gondii infection could act as a potential risk factor for ASD. However, further intensive studies are necessary to clarify the role of this parasite in the etiology and progression of ASD. This review is anticipated to stimulate further studies aimed at understanding and potentially reducing the burden of neurodevelopmental disorders worldwide.

Lien vers le texte intégral (Open Access ou abonnement)

11. Grzeszak A, Pisula E. Correction: Experiences of females on the autism spectrum through the perspective of minority stress theory: a review. Front Psychiatry;2025;16:1672758.

[This corrects the article DOI: 10.3389/fpsyt.2025.1578963.].

Lien vers le texte intégral (Open Access ou abonnement)

12. Jiang Y, Zhu F, Zhong J, Sun X, Yuan Y, Wang S, Chen H, Xu Z. Autism-related proteins form a complex to maintain the striatal asymmetry in mice. Cell Res;2025 (Sep 2)

The brain’s hemispheres exhibit profound lateralization, yet the underlying mechanisms remain elusive. Using proteomic and phosphoproteomic analyses of the bilateral striatum – a hub for important brain functions and a common node of autism pathophysiology – we identified significant phosphorylation asymmetries. Particularly, the phosphorylation processes in the left striatum appear more prone to disturbance. Notably, SH3RF2, whose single-copy knockout leads to autism spectrum disorder (ASD)-like behaviors in mice, is uniquely expressed in the striatum, forming a complex with CaMKII (an ASD-associated protein) and PPP1CC. Loss of SH3RF2 disturbs the CaMKII/PP1 « switch », resulting in hyperactivity of CaMKII and increased phosphorylation of its substrate GluR1. In Sh3rf2-deficient mice, heightened GluR1-Ser831 phosphorylation and its aberrant postsynaptic membrane localization in the left striatum may impair the functional lateralization of striatal neurons and contribute to autism-like behaviors. This study unveils the first molecular mechanism governing brain lateralization in mammals, linking its impairment to autism development and treatment strategies.

Lien vers le texte intégral (Open Access ou abonnement)

13. Kaneko N, Higuchi Y, Tsujii N, Nishiyama S, Akasaki Y, Nagasawa K, Sasabayashi D, Suzuki M, Takahashi T. Features of mismatch negativity in an at-risk mental state with the traits associated with the autistic spectrum. Front Psychiatry;2025;16:1620954.

INTRODUCTION: Accurately distinguishing individuals with autism spectrum disorder (ASD) from those with schizophrenia spectrum disorder (SSD) can be challenging, especially in individuals with an at-risk mental state (ARMS) for psychosis. Given the need for objective markers, we focused on mismatch negativity (MMN). This study aimed to determine whether ARMS individuals with ASD traits exhibit different MMN patterns compared to ARMS individuals without such traits and healthy controls. METHODS: Forty-nine individuals with ARMS and 45 healthy controls were enrolled. The Autism-Spectrum Quotient Japanese Version (AQ-J) was used to assess ASD traits, with a cut-off of 33+ indicating high ASD traits [AQ(+)] and scores below that low ASD traits [AQ(-)]. An electroencephalogram was recorded while the participants heard standard and deviant tones in two auditory oddball paradigms: a duration-deviant (dMMN) and a frequency-deviant (fMMN). MMN amplitude and latency were analyzed at Fz and group differences were compared between patients with ARMS and healthy controls. Further, within the ARMS group, AQ(-) (n = 33) vs. AQ(+) (n = 16) subgroups were examined. Correlation analyses were also performed to explore the relationships between MMN measures and clinical/cognitive indices. RESULTS: No significant differences in MMN amplitude or latency were observed between the ARMS group and healthy controls. In contrast, fMMN latency in the AQ (+) group was significantly shorter than that in the AQ(-) group. Within the entire ARMS group, fMMN latency had a significant negative correlation with total AQ-J scores, especially the Communication subscale, i.e., higher ASD traits were associated with shorter fMMN latency. CONCLUSION: The key finding of this study was that ARMS individuals with higher ASD traits showed a shortened fMMN latency compared to those without. Distinguishing ARMS from ASD based solely on clinical symptoms is sometimes difficult, and using an objective measurement tool such as MMN latency could help identify underlying ASD features and guide more tailored interventions.

Lien vers le texte intégral (Open Access ou abonnement)

14. Kidwell JL. ADHD and autism in Neurocognitive Mismatch Theory: distinct neurodevelopmental incompatibilities with the market-based system. Front Psychol;2025;16:1617192.

ADHD and Autism Spectrum Disorder (ASD) represent distinct neurodevelopmental conditions with unique profiles, yet they share susceptibility to environmental pressures that may exacerbate cognitive mismatches. This paper argues that Attention-Deficit/Hyperactivity Disorder and Autism Spectrum traits are not fixed neurological disorders but neurodevelopmental variants destabilized by the sociobiological mismatch between evolved human cognition and the pressures of modern market-based civilization. Drawing on evolutionary biology, developmental neuroscience, social epidemiology, and political economy, the paper reframes these conditions as context-contingent outcomes: traits that are biologically conserved due to their adaptive value in ancestral environments but rendered dysfunctional under chronic stress, inequality, overstimulation, environmental toxicity, and cognitive suppression endemic to industrial societies. It synthesizes evidence across prenatal programming, intergenerational stress transmission, pharmaceutical ethics, and neuroplastic adaptation to propose an ecological model in which the environment, not the brain, is the primary source of pathology. This reframing calls for systemic transformation, not individual correction, and provides a foundation for more inclusive, developmentally respectful, and ecologically coherent mental health paradigms.

Lien vers le texte intégral (Open Access ou abonnement)

15. Kim TH, Youn SE, Chung SH. Longitudinal Analysis of Growth and Neurodevelopmental Outcomes in Very Low Birth Weight Infants With Congenital Anomalies Over Three Years. J Korean Med Sci;2025 (Sep 1);40(34):e254.

BACKGROUND: Very low birth weight infants (VLBWIs) are vulnerable to growth restrictions and neurodevelopmental impairments. Congenital anomalies further complicate these risks; however, their long-term effects remain unclear. This study examined the impact of congenital anomalies on the growth and neurodevelopment of VLBWIs. METHODS: This prospective cohort study analyzed data from the Korean Neonatal Network (2013-2017). A total of 172 VLBWIs with congenital anomalies were matched by gestational age to 516 without anomalies at 18-24 months corrected age, and 136 were matched to 408 at 3 years of age. Growth was assessed using WHO standards, and neurodevelopment was evaluated using the Bayley Scales of Infant Development (II/III) and Korean Developmental Screening Test. Logistic regression analyses were used to identify factors associated with adverse outcomes, with statistical significance set at P < 0.05. RESULTS: VLBWIs with congenital anomalies had significantly lower weight, height, and head circumference z-scores at both time points. Growth restriction persisted, and neurodevelopmental delays, particularly in motor function, were more prevalent. Infants with multiple congenital anomalies had the highest risk of severe growth restriction and developmental impairment. CONCLUSION: Congenital anomalies pose significant challenges to the growth and neurodevelopment of VLBWIs. Early and individualized interventions, structured neurodevelopmental follow-up, and multidisciplinary care are essential for improving long-term outcomes.

Lien vers le texte intégral (Open Access ou abonnement)

16. Marcantonio W, Simonti M, Léna I, Mantegazza M. Sex-Specific Behavioral Features of Juvenile and Adult Haploinsufficient Scn2a(+/-) Female Mice, Model of Autism Spectrum Disorder. Genes Brain Behav;2025 (Oct);24(5):e70034.

Genetic variants of the SCN2A gene, encoding the Na(V)1.2 sodium channel, cause a spectrum of neurodevelopmental and epileptic disorders, and are among those that show the strongest association with Autism Spectrum Disorder (ASD). ASD has a male-bias prevalence, but several studies have proposed that female prevalence may be underestimated due to different symptomatic expression compared with males. However, it is unclear whether this is related to actual different pathological features or to greater masking abilities in females. Studies on Scn2a(+/-) mice, a model of SCN2A haploinsufficiency and ASD, have shown an age-dependent ASD-like phenotype attenuated at adulthood in males. However, little is known about the behavioral features of Scn2a(+/-) female mice. We performed a battery of behavioral tests that are relevant for assessing ASD-like features, investigating juvenile and adult Scn2a(+/-) female mice. Our results demonstrate that female Scn2a(+/-) mice exhibit an overall milder phenotype than males, showing increased risk-taking in juveniles, hyper-reactivity to cold stimuli, and mild memory impairments in adults, abnormally increased sociability, and altered decision-making related behaviors in both juveniles and adults. Thus, this aligns with the male-biased prevalence of ASD and supports the existence of sex-specific phenotypic differences, potentially arising from distinct underlying pathophysiological mechanisms. Both sexes should be investigated in studies of mouse models of ASD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Montazeri F, Liu YA, Emami-Naeini P. Retinal Structures in Autism Spectrum Disorder: Results from a Case-Control Study. Ophthalmol Sci;2025 (Nov-Dec);5(6):100842.

OBJECTIVE: To assess retinal structures in patients with autism spectrum disorder (ASD) and its correlation with cognitive impairments and brain volumes. DESIGN: A retrospective case-control study. SUBJECTS: Adults with ASD and matched neurotypical controls were identified from the UK Biobank (UKBB). The exclusion criteria included a history of neurodegenerative diseases, optic nerve pathology, retinal disorders, glaucoma surgery, high refractive error, or intraocular pressure outside the range of 6 to 21 mmHg. METHODS: Using OCT images, 9 distinct retinal layers were segmented: the retinal nerve fiber layer (RNFL), ganglion cell layer, inner plexiform layer, inner nuclear layer (INL), combined outer plexiform layer and outer nuclear layer, photoreceptor inner segment, photoreceptor outer segment, retinal pigment epithelium, and choroidoscleral interface. Cognitive function was evaluated using 4 standardized tests: pairs matching, prospective memory, numerical or verbal reasoning, and reaction time. Additionally, brain imaging-derived phenotypes from the UKBB were included in the analysis. Generalized linear models were used to evaluate associations. MAIN OUTCOME MEASURES: Differences in retinal layer thickness between autistic individuals and controls, and the association with cognitive impairment and brain volumes. RESULTS: We examined 240 eyes, including 80 from autistic participants and 160 from matched neurotypical controls. Autistic participants showed significantly higher thickness in the inner retina (adjusted mean differences: 5.71 μm, 95% confidence interval [2.49-8.93], P = 0.001), as well as RNFL (2.52 μm [0.97-4.06], P = 0.001), inner plexiform layer (1.18 [0.28-2.07], P = 0.010), and INL (0.93 [0.22-1.66], P = 0.010). No significant correlation was found between inner retinal thickness and cognitive impairment. However, brain magnetic resonance imaging data indicated associations between inner retinal thickness and volumes of the total brain, corpus collosum, hippocampus, and temporal gyrus. CONCLUSIONS: The inner retina may offer valuable insights into neurodevelopmental features in ASD, with observed associations with specific brain volumetric measurements. These findings could inform future research on ASD diagnostics and treatment. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Lien vers le texte intégral (Open Access ou abonnement)

18. Nakamura T, Dobashi R, Noda H, Ikeda K, Nagayama H, Sasada S. Sensory subtypes of children on the autism spectrum in Japan: Characteristics of participation and family functioning. Autism;2025 (Sep 2):13623613251357835.

This study aimed to identify sensory subtypes in preschool children on the autism spectrum in Japan and examine their associations with participation and family functioning. A total of 264 caregivers of preschool children aged 3-6 years on the autism spectrum participated in the study. Data were collected from 56 child development centers and medical institutions across Japan. Sensory features were assessed using the Japanese version of the Short Sensory Profile, and five sensory subtypes were identified: Taste/Smell Sensitive, Extremely Atypical, Mixed Sensory, Gravitational Insecurity and Motor Difficulty, and Adaptive. These subtypes were associated with distinct participation restrictions, such as activities of daily living (ADL)-related challenges in the Mixed Sensory group, leisure-related difficulties in the Taste/Smell Sensitive group, and limitations across all domains in the Extremely Atypical group. Significant differences in family functioning were also observed in domains related to interaction with the external environment of the family, with the Extremely Atypical group showing support needs. These findings underscore the importance of developing tailored intervention strategies for each sensory subtype.Lay abstractThis study examined the impact of differences in sensory processing on the daily lives of preschool children with autism spectrum disorder in Japan, as well as how these differences influence their families. Caregivers of children aged 3-6 years from 56 centers and medical institutions took part in the study. Through a questionnaire, we identified five sensory types among the children: those sensitive to taste and smell, those with highly unusual sensory responses, those with a mix of sensory challenges, those struggling with balance and movement, and those with more adaptive sensory responses. Each sensory type encountered specific challenges in daily activities. For example, children with mixed sensory challenges had difficulties with basic tasks such as eating or dressing, while those sensitive to taste and smell faced challenges in leisure activities. Children with highly unusual sensory responses experienced difficulties in all areas of daily life. These challenges also impacted family dynamics, especially in how families engaged with their surroundings. Families of children with highly unusual sensory responses often required additional support. Our findings emphasize the necessity for personalized support and intervention strategies tailored to each child’s unique sensory subtype, which can enhance their participation in daily activities and promote their family’s well-being.

Lien vers le texte intégral (Open Access ou abonnement)

19. Northrup JB, Nuske HJ, Hipwell AE, Mazefsky CA. Review and Developmental Model: Early Childhood Emotion Regulation and Co-Regulation in Autism. J Am Acad Child Adolesc Psychiatry;2025 (Sep 2)

OBJECTIVE: Emotion regulation (ER) and dysregulation (ED) significantly impact the mental health and quality of life of autistic individuals and their families, yet little is known about ER development in early childhood autism. This paper proposes a developmental model of disruptions to early ER development, emphasizing parent-child co-regulation, to guide future research and clinical care. METHOD: Empirical research on ER, ED, and parent-child co-regulation in young autistic children (mean age < 6 years) was summarized. Insights from theoretical and empirical work on typical ER development, with a focus on parent-child co-regulation, were integrated with autism research to propose a novel developmental model. RESULTS: Research on ER and ED in young autistic children remains limited and lacks a developmental framework. Parent-child co-regulation is identified as a key mechanism in ER development, operating across micro (moment-by-moment) and macro (long-term) time scales. Autism-specific challenges, such as pervasive and idiosyncratic triggers, reduced emotional awareness, and ambiguous emotional communication, can disrupt parent-child co-regulation. These disruptions reduce opportunities for teaching and internalizing effective ER strategies and can lead parents and children to rely on "quick fix" strategies (e.g., avoidance), ultimately hindering long-term ER development and negatively impacting mental health. CONCLUSION: Understanding disruptions to ER development in autism within parent-child interactions offers a framework for research and clinical care. Developing autism-specific measurement tools and employing longitudinal, ecological, and "measurement burst" designs will be critical to uncovering disrupted dyadic processes. Future research and clinical efforts must address the unique experiences and needs of autistic children and their families.

Lien vers le texte intégral (Open Access ou abonnement)

20. Ptacek MM, Smith LD, Powell RM, Mitra M. Experiences with and Perceptions of the Child Welfare System During the Perinatal Period of Mothers with Intellectual and Developmental Disabilities. J Public Child Welf;2025;19(4):751-773.

BACKGROUND AND PURPOSE: Mothers with intellectual and developmental disabilities (IDD) face compounding disparities within perinatal and child welfare systems, yet their experiences at this critical intersection remain understudied. MATERIALS AND METHODS: This qualitative study interviewed 16 mothers with IDD who recently gave birth to explore their perceptions and encounters with the child welfare system during the perinatal period. RESULTS: Adverse themes emerged surrounding (a) fear of having children removed, (b) wariness of the healthcare system from some mothers, though others viewed providers as supportive, (c) insufficient assistance, and (d) trauma and stress. Conversely, positive themes included (a) support from others, including certain healthcare providers viewed as protective, and (b) believing in oneself. DISCUSSION: The findings underscore pervasive bias and lack of disability cultural competence across both systems, compounding adverse perinatal outcomes for this population. CONCLUSION: Improving equitable care necessitates comprehensive policy reforms mandating professional training on disability, non-discriminatory practices, and strengths-based family preservation approaches. Implications span enhancing disability cultural competence through provider training, increasing supportive services, promoting self-advocacy and empowerment, and prioritizing family-centered, individualized care models guided by the disability community’s insights. An expansive research agenda is also urgently needed.

Lien vers le texte intégral (Open Access ou abonnement)

21. Ramachandran S, Stensland S, Corder JH, Cuomo C, Dao TV, Natowicz MR. Adolescent to adult health care transition for persons with intellectual and developmental disability: current barriers, next steps. Front Pediatr;2025;13:1486325.

The transition of health care from adolescence to adulthood is a challenging time, especially for persons with intellectual and developmental disability (IDD), where navigating health care transitions can be particularly difficult. Persons with IDD are an especially vulnerable population and they and their caregivers encounter barriers in obtaining high quality health care transition. These barriers result in the suboptimal utilization of health care transition services and consequent poorer health outcomes. Herein, we discuss barriers to obtaining high quality pediatric to adult transitional health care for persons with IDD. We then discuss next steps, some of them well recognized and others underappreciated, for addressing these barriers and thereby achieving an important public health need: the attainment of high quality pediatric to adult health care transition for persons with IDD.

Lien vers le texte intégral (Open Access ou abonnement)

22. Seda MS, Rios NP, Tumanyan SR, Negron DM, Lopez Del Valle LM. Oral Health Indicators among a sample of Hispanic Patients diagnosed with Autism Spectrum Disorder. Rev Odontopediatr Latinoam;2025 (Mar 12);15

OBJECTIVE: This study aimed to determine the oral health and the associated health disparities of pediatric patients with autism spectrum disorder (ASD). METHODS: This non-matched, case-control study recruited 22 subjects diagnosed with ASD (cases) and 27 without ASD (controls) aged 5-18 years. Two calibrated dentists performed dental exams for caries and gingivitis on all subjects. Parents/caregivers completed sociodemographics and social determinants oral health questionnaires. As appropriate, between-group comparisons were performed using chi-square, Fisher’s exact test, t-test, and Mann-Whitney test. Associations between ASD and oral health indices were determined using logistic, Poisson, and linear regression models. RESULTS: Statistically significant differences were found for not easy finding dental services for ASD patients (p=0.014) and behavioral problems during dental visits (p=0.012). Children with ASD had significantly lower odds of caries (DMFT+dft>0) compared to children without ASD (OR=0.121; 95% CI: 0.023; 0.636). Age- and sex-adjusted models showed a significantly lower gingival index among those with ASD. CONCLUSION: ASD patients had better oral health indices than the control subjects. The barriers to treatment for ASD patients were lack of access to dental care and living in a rural area.

Lien vers le texte intégral (Open Access ou abonnement)

23. Shetty N, Brown WD, Massingham L, Rogg J, Quintos JB. Noonan Syndrome and Rett Syndrome in An 8-Year-Old Girl With A Tectal Neoplasm. JCEM Case Rep;2025 (Oct);3(10):luaf188.

Individuals with Noonan syndrome (NS) are predisposed to hematologic cancers, solid tumors, and low-grade gliomas. We report an 8-year-old girl originally referred at age 14 months for short stature, developmental delay, and failure to thrive who was subsequently found to have pathogenetic variants both in MECP2 and PTPN11. Family history included a maternal half-sister with NS and a mother carrying the PTPN11 mutation. Familial single-gene testing showed a heterozygous pathogenic variant in PTPN11 (c.417G > C p.Glu139Asp) suggesting NS, prompting initiation of growth hormone (GH) treatment at 26 months. Due to associated language delays, gross motor delays, microcephaly, and seizures, exome sequencing (ES) was pursued. ES identified a heterozygous de novo pathogenic variant (c.763C > T p.Arg255Ter) in MECP2 and led to the additional diagnosis of Rett syndrome (RTT). Seizure onset prompted neuroimaging, which demonstrated hydrocephalus due to aqueductal stenosis secondary to a tectal neoplasm. GH treatment was discontinued. The co-occurrence of NS and RTT is rare. ES enabled the additional diagnosis of RTT in our patient with NS, who presented with atypical features and developmental regression.

Lien vers le texte intégral (Open Access ou abonnement)

24. Solomon M, Yon-Hernández JA, Ruder S, McGurk SR, Tancredi D, Takarae Y, Stahmer AC. A randomized controlled trial protocol for evaluating the feasibility, acceptability, and work outcomes of individualized placement and support adapted for autistic adults in the community. Contemp Clin Trials Commun;2025 (Oct);47:101536.

Relatively few autistic adults, including those with average intellectual abilities, are competitively employed, meaning that they hold jobs together with non-disabled workers and receive comparable wages and benefits. In California, for example, most autistic individuals served by the state are placed in programs where they participate in skill-building and socialization but not in actual competitive jobs. Failure to participate in the labor force can diminish autistic workers’ sense of purpose, well-being, and ability to earn a living wage. Available research suggests that supported employment that assists autistic adults in finding and keeping jobs, produces the highest sustained competitive employment rates. Thus, our team has been investigating the Individualized Placement and Support (IPS) model, which has an extensive evidence base for increasing competitive employment rates in individuals with chronic mental illnesses. In a California Department of Developmental Services Employment Grant investigating adults with autism and intellectual disabilities, we demonstrated a competitive employment placement rate of 52 % using IPS. Components of IPS were appropriate for this population, however there were implementation challenges related to IPS model fit with the vocational support agencies. Based on focus groups and stakeholder input, we have adapted IPS to provide intensive agency training, leadership education, and record keeping support. Herein, we detail a protocol for a randomized controlled trial of the adapted model (IPS-AUT) to evaluate feasibility, acceptability, and work outcomes. We also investigate potential moderators and mediators of treatment effectiveness to provide a foundation for a larger more adequately powered randomized clinical trial. This protocol is registered at ClinicalTrials.gov: NCT06829264.

Lien vers le texte intégral (Open Access ou abonnement)

25. Soria F, Mari A, Moschini M, Naspro R, Hurle R, Miglioranza E, Lapini A, Antonelli A, Tubaro A, Volpe A, Bartoletti R, Gontero P, Carrieri G, Ficarra V. The current role of photodynamic diagnosis (PDD) in the management of non-muscle invasive bladder cancer: the Italian Society of Urology (SIU) Position Paper. Minerva Urol Nephrol;2025 (Aug);77(4):443-450.

Photodynamic diagnosis (PDD) significantly enhances the detection of bladder cancer (BCa) and is able to reduce the risk of disease recurrence, although it may not affect disease progression and mortality rates. Despite its advantages, widespread adoption of PDD is limited by cost considerations and the absence of unified guidelines on its application, highlighting the need for continued evaluation of its cost-effectiveness across different healthcare settings. To date, no specific recommendations for PDD in non-muscle invasive bladder cancer (NMIBC) management have been provided by the Italian Society of Urology (Società Italiana di Urologia, SIU). Therefore, the aim of this paper is to report on the position of SIU on the role of PDD in NMIBC. According to available evidence and international guidelines (i.e., European Association of Urology, American Association of Urology, National Comprehensive Cancer Network and other national guidelines) on BCa, a Panel of twelve Italian urologists with long and renowned experience in treating BCa defined current indications for PDD in the management of NMIBC. The final document was ultimately reviewed and approved by the expert Panel prior to publication. The consensus highlighted the role of PDD during the initial transurethral resection of the bladder (TURB) to detect carcinoma in situ (CIS) and small papillary lesions that might otherwise be missed, leading to disease persistence. Additionally, in clinical scenarios such as positive urine cytology with negative cystoscopy, PDD-guided biopsies can significantly increase the detection of CIS. For cases involving larger or multifocal tumors, or atypical macroscopic features during cystoscopy, PDD is valuable for identifying subtle high-grade disease elements, thereby facilitating more precise risk stratification and targeted treatment planning. In the setting of re-TURB, aiming to detect the presence and extent of concomitant CIS and to gain all possible additional information, PDD may be used in all procedures if not already performed during initial resection. Finally, PDD may be used for disease recurrence in patients with a history of HG NMIBC and to evaluate the response of CIS to Bacillus Calmette-Guérin (BCG). This position paper of the SIU highlights the current recommendation for the use of PDD in the management of NMIBC, from initial TURB, to re-TURB and follow-up.

Lien vers le texte intégral (Open Access ou abonnement)

26. Thomas KE, Raghuram K, Banihani R, Church PT, Mbuagbaw L, Penner M. Screening for Autism in Preterm Children: A Systematic Review. Pediatrics;2025 (Sep 3)

OBJECTIVE: Preterm children exhibit a higher prevalence of autism spectrum disorder (ASD) than the general population. The unique neurodevelopmental characteristics of preterm children present challenges in screening for and diagnosing ASD. To date, a systematic review of screening tools for ASD in this population has not been completed. This systematic review and meta-analysis evaluates the diagnostic performance of currently used ASD screening tools in the preterm population. METHODS: The database search was conducted by using MEDLINE, PsycINFO, PubMed, Embase, and CINAHL in July 2024. Articles that quantified the diagnostic accuracy of ASD screening tools in the preterm population were included. Nine studies were included in this review, and only 4 studies in the meta-analyses. All studies were assessed for risk of bias, applicability, and certainty. RESULTS: Sensitivity of screening tools for ASD in preterm children ranged from 0% to 100%, whereas specificity ranged from 38% to 98%. Pooled data were available for the Modified Checklist for Autism in Toddlers (2 studies) and Social Communication Questionnaire. (2 studies), with pooled sensitivities of 55% and 53% and specificities 85% and 90%, respectively. CONCLUSIONS: There was significant study heterogeneity, limiting the number of studies from which to pool diagnostic accuracy data. Screening tools vary in their ability to identify ASD in the preterm population, underscoring how overlapping behavioral phenotypes may confound early identification. There is a critical need to refine and assess ASD screening tools in preterm children, facilitating timely interventions in this cohort.

Lien vers le texte intégral (Open Access ou abonnement)

27. Zaidman-Zait A, Hollocks MJ, Kerns CM, Magiati I, McVey AJ, Smith IM, Bedford R, Bennett T, Duku E, Georgiades S, Richard A, Vaillancourt T, Zwaigenbaum L, Hardan A, Libove R, Rodgers J, South M, Simonoff E, Van Hecke A, Uljarević M, Szatmari P. Bridging the gap: unveiling key links between autism and anxiety symptoms in autistic children and youth using a network analysis in pooled data from four countries. Child Adolesc Ment Health;2025 (Sep 2)

BACKGROUND: Autistic children experience significantly higher rates of anxiety compared to nonautistic children. The precise relations between autism characteristics and anxiety symptoms remain unclear in this population. Previous work has explored associations at the domain level, which involve examining broad categories or clusters of symptoms, rather than the relationships between specific symptoms and/or individual characteristics. We addressed this gap by taking a network approach to understand the shared structure of autism characteristics and anxiety symptoms. METHOD: Data were pooled from five studies from Canada, Singapore, the UK, and the USA, totaling 623 autistic children (17% female sex; aged 6-18 years), for whom the parent-report Spence Children’s Anxiety Scale (SCAS-P) was available. We derived two undirected regularized networks, first from the SCAS-P items only, and then by adding autism characteristics pertaining to social communication, highly focused and repetitive behavior, and sensory hypersensitivity. From these models’ metrics, we extracted nodes’ predictability, key bridging nodes, and community detection. RESULTS: The anxiety-only network was highly connected and consisted of four key clusters: General Anxiety, Social Anxiety, Separation Anxiety, and Panic/Agoraphobia. These broadly aligned with the existing SCAS-P structure based on DSM-IV-TR criteria. In the autism-anxiety network, the structure of anxiety remained mostly stable, with autism features forming their own community. Preference for predictability (i.e., sameness) and sensory hypersensitivity were key nodes that linked autistic features and anxiety symptoms, primarily through generalized anxiety. CONCLUSION: This study identified some of the key characteristics that bridge the broadly independent structures of autism characteristics and anxiety symptoms. The findings are discussed in the context of guiding the assessment, prevention, and treatment of anxiety in autism.

Lien vers le texte intégral (Open Access ou abonnement)

28. Zhang DY, Wei QH, Hu BY, Ai D, Zhang Y, Ding Y, Yang T, Chen J, Chen L, Wu Y, Chen HY, Xiang XL, Mou QH, Li TY. The value of intellectual structural imbalance in the differentiation of autism spectrum disorder and attention deficit hyperactivity disorder. Front Psychiatry;2025;16:1610278.

BACKGROUND: The study delves into the intricate task of differentiating intellectual structures among children diagnosed with the high-functioning Autism Spectrum Disorder (HF-ASD), Attention Deficit Hyperactivity Disorder (ADHD), or comorbidity (ASD+ADHD), aiming to assist in their clinical differentiation, with the goal of refining clinical diagnoses and developing targeted therapeutic interventions. METHODS: The study included 200 outpatients aged 6.5-13.0 years (total Intelligence Quotient (IQ) 70-130) at the Children’s Hospital of Chongqing Medical University, and categorized into HF-ASD (n=91), ADHD (n=47), and comorbidity ASD+ADHD (n=62) groups. We utilized the Chinese Wechsler Intelligence Scale for Children (C-WISC) as the primary assessment tool, supplemented by additional diagnostic measures. Besides, we used SPSS 25.0 to assess the subtest scores and differences. RESULTS: The comorbidity group had lower total IQ than the other two groups (p<0.001). The verbal IQ(VIQ) were lower than the performance IQ(PIQ) in HF-ASD (p=0.017) and comorbidity (p=0.007) groups. They also scored higher on perceptual organization subtests particularly in Block Design and Object Assembly than the ADHD group. The ADHD group showed higher VIQ than PIQ (p=0.020). The ADHD group's scores for working memory subtests were lower than in the HF-ASD group. The respective peak scores for the HF-ASD and comorbidity groups were in Block Design (45%,43%) and Object Assembly (30%,37%) and valleys in Picture Completion (52%,24%), Information (HF-ASD 24%), and Arithmetic (comorbidity 42%). CONCLUSION: The peak-valley difference in the ADHD group (~2 standard deviations) was smaller than in the HF-ASD and comorbidity groups (~3 standard deviations), and this characteristic could help differentiate between HF-ASD, ADHD, and both together.

Lien vers le texte intégral (Open Access ou abonnement)

29. Zhang Y, Ahsan MU, Wang K. Noncoding de novo mutations in SCN2A are associated with autism spectrum disorders. iScience;2025 (Sep 19);28(9):113258.

Previous genetic studies in Autism Spectrum Disorder (ASD) identified hundreds of high-confidence ASD genes enriched with likely deleterious protein-coding de novo mutations (DNMs). Multiple studies also demonstrated that DNMs in the non-coding genome can contribute to ASD risk. However, the identification of individual risk genes enriched with noncoding DNMs has remained largely unexplored. We analyzed two datasets with over 5000 ASD families to assess the contribution of noncoding DNMs. We used two methods to assess statistical significance for noncoding DNMs: a point-based test that analyzes sites that are likely functional, and a segment-based test that analyzes 1 kb genomic segments with segment-specific background mutation rates. We found that coding and noncoding DNMs in SCN2A are associated with ASD risk. Further application of these approaches on large-scale whole genome sequencing data will help identify additional candidate ASD risk genes.

Lien vers le texte intégral (Open Access ou abonnement)

30. Zhou YH, Sun G. Organophosphate Flame Retardants Disrupt Neurodevelopmental Gene Networks with Autism-Relevant Features: A Multi-Omics Study in Rats. Environ Res;2025 (Sep 2):122734.

Organophosphate flame retardants (OPFRs) are widely used environmental contaminants with suspected developmental neurotoxicity, yet their stage-specific molecular impacts and potential relevance to autism spectrum disorder (ASD) remain poorly defined. We integrated transcriptomic and lipidomic analyses from two rat models to investigate OPFR-induced disruption across early neurodevelopment. In dataset GSE148266, fetal forebrain and placenta were analyzed following in utero OPFR exposure; in dataset GSE211430, neonatal cortical RNA-seq and lipidomics were profiled after postnatal exposure to triphenyl phosphate and isopropylated triaryl phosphate (1,000 μg/day; n = 10/sex/group). Differential expression (DESeq2; FDR < 0.05), pathway enrichment (GSEA), and multi-omics integration (DIABLO; |r| > 0.9) were performed. Fetal exposure altered 191 genes (144 mapped to human orthologues), including ASD-relevant genes such as ADNP, BRAF, and MAPK3, with enrichment in spliceosome (NES = 2.39), cell-cycle regulation (NES = 2.26), and suppressed Toll-like/NOD-like immune signaling (NES = -2.06). Postnatal exposure disrupted 34 genes and 12 lipids, notably PC(15:0_16:0) and TG(18:1_20:1_20:1), which correlated with synaptic and immune-related genes. Eighteen neonatal DEGs overlapped with human ASD cortical transcriptomes, and integrated analysis revealed shared neurotransmission networks across developmental stages. These findings demonstrate that OPFRs disrupt conserved neurodevelopmental gene networks in a stage-specific manner. The convergence of transcriptomic and lipidomic signals with ASD-relevant features supports further investigation of OPFRs as candidate environmental risk factors and highlights molecular pathways for future biomarker and toxicity studies.

Lien vers le texte intégral (Open Access ou abonnement)