1. Antonatos C, Pontikas A, Akritidis A, Mitsoudi D, Georgiou S, Stratigos AJ, Zacharopoulou A, Gregoriou S, Grafanaki K, Vasilopoulos Y. A genome-wide pleiotropy study between atopic dermatitis and neuropsychiatric disorders. Hum Genomics;2025 (Jul 25);19(1):86.

Atopic dermatitis (AD) frequently co-occurs with neuropsychiatric disorders, yet the genetic basis for this comorbidity is unclear. We performed a large-scale genome-wide pleiotropy approach to investigate the genetic correlations and causal associations between AD and five neuropsychiatric disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia (SCZ). We identified significant positive genetic correlations between AD and ADHD, MDD and BP. Genome-wide pleiotropy scans identified 37 distinct pleiotropic loci, mapped in 86 unique genes participating in inflammatory pathways. Pleiotropy-informed target prioritization facilitated the identification of novel pathophysiological mechanisms for AD and putative drug targets, such as members of TNF and JAK-STAT3 signaling. Mendelian randomization provided evidence of a causal relationship between genetic liability to MDD and BP in increased AD risk, independent of sample overlap. Our findings elucidate immune-related pathway crosstalks between AD and neuropsychiatric disorders with implications for therapeutic interventions.

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2. Bai M, Xiao J, Zhao T, Chen R, Xue Y, Mohamed ZA, Jia F, Dong H. Associations between sleep problems, cortical morphometry, and structural brain network organization in preschool children with autism: a retrospective observational study. Eur J Pediatr;2025 (Jul 28);184(8):506.

Sleep problems are highly prevalent in autism spectrum disorder (ASD) and may contribute to behavioral challenges and atypical brain development. However, the neuroanatomical mechanisms linking sleep problems and ASD during early childhood remain underexplored. This retrospective observational study included 183 preschool children with ASD, grouped by sleep problem status using the Children’s Sleep Habits Questionnaire (CSHQ). Structural MRI data were processed with FreeSurfer to obtain cortical volume measures across 68 regions. Structural covariance networks were constructed to assess topological properties using graph theory. Group comparisons and exploratory correlation analyses were conducted to evaluate associations with behavioral measures. No significant group differences were found in total cortical or subcortical volumes. Exploratory analyses revealed uncorrected focal differences in the peri-calcarine cortex and right pars orbitalis, but these did not survive correction for multiple comparisons. Network analyses showed significantly reduced local connectivity (clustering coefficient, local efficiency) and altered small-world topology (Gamma, Sigma) in children with sleep problems, with preserved global efficiency. Exploratory correlations suggested that regional volumes may be linked to repetitive behaviors and withdrawn symptoms, although these did not remain significant after correction. CONCLUSION: Preschool children with ASD and sleep problems show disrupted local brain network properties, particularly in sensory and social-cognitive regions. While some regional associations with behavior were observed, they should be interpreted cautiously due to their exploratory nature. These findings support the importance of considering sleep in neurodevelopmental assessments and highlight the need for longitudinal studies with objective sleep measures. WHAT IS KNOWN: • Sleep problems are highly prevalent in children with autism spectrum disorder (ASD) and are linked to adverse behavioral outcomes. • Structural covariance networks (SCNs) reflect coordinated brain development and are altered in ASD. WHAT IS NEW: • This study explores associations between sleep problems and both cortical morphology and SCNs in preschoolers with ASD. • Exploratory analyses reveal regional volume trends and altered network topology in children with sleep problems, suggesting potential early neural correlates.

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3. Chen X, Peng J, Zhang Z, Song Q, Li D, Zhai G, Fu W, Shu Z. Constructing a predictive model for children with autism spectrum disorder based on whole brain magnetic resonance radiomics: a machine learning study. AJNR Am J Neuroradiol;2025 (Jul 28)

BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) diagnosis remains challenging and could benefit from objective imaging-based approaches. This study aimed to construct a prediction model using whole-brain imaging radiomics and machine learning to identify children with ASD. MATERIALS AND METHODS: We analyzed 223 subjects (120 with ASD) from the ABIDE database, randomly divided into training and test sets (7:3 ratio), and an independent external test set of 87 participants from Georgetown University and University of Miami. Radiomics features were extracted from white matter, gray matter, and cerebrospinal fluid from whole-brain MR images. After feature dimensionality reduction, we screened clinical predictors using multivariate logistic regression and combined them with radiomics signatures to build machine learning models. Model performance was evaluated using ROC curves and by stratifying subjects into risk subgroups. RESULTS: Radiomics markers achieved AUCs of 0.78, 0.75, and 0.74 in training, test, and external test sets, respectively. Verbal intelligence quotient(VIQ) emerged as a significant ASD predictor. The decision tree algorithm with radiomics markers performed best, with AUCs of 0.87, 0.84, and 0.83; sensitivities of 0.89, 0.84, and 0.86; and specificities of 0.70, 0.63, and 0.66 in the three datasets, respectively. Risk stratification using a cut-off value of 0.4285 showed significant differences in ASD prevalence between subgroups across all datasets (training: χ(2)=21.325; test: χ(2)=5.379; external test: χ(2)=21.52m, P<0.05). CONCLUSIONS: A radiomics signature based on whole-brain MRI features can effectively identify ASD, with performance enhanced by incorporating VIQ data and using a decision tree algorithm, providing a potential adaptive strategy for clinical practice. ABBREVIATIONS: ASD = Autism Spectrum Disorder; MRI = Magnetic Resonance Imaging; SVM = support vector machine; KNN = K-nearest neighbor; VIQ = Verbal intelligence quotient; FIQ = Full-Scale intelligence quotient; ROC = Receiver Operating Characteristic; AUC = Area under Curve.

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4. Cuddapah VA, Chen D, Cho B, Moore R, Suri M, Safraou H, Tran-Mau-Them F, Wilson A, Odgis J, Rehman AU, Saunders C, Ganesan S, Jobanputra V, Scherer SW, Helbig I, Sehgal A. Rare variants in BMAL1 are associated with a neurodevelopmental syndrome. Proc Natl Acad Sci U S A;2025 (Aug 5);122(31):e2427085122.

Through international gene-matching efforts, we identified 10 individuals with ultrarare heterozygous variants, including 5 de novo variants, in BMAL1, a core component of the molecular clock. Instead of an isolated circadian phenotype seen with disease-causing variants in other molecular clock genes, all individuals carrying BMAL1 variants surprisingly share a clinical syndrome manifest as developmental delay and autism spectrum disorder, with variably penetrant sleep disturbances, seizures, and marfanoid habitus. Variants were functionally tested in cultured cells using a Per2-promoter driven luciferase reporter and revealed both loss-of-function and gain-of-function changes in circadian rhythms. The tested BMAL1 variants disrupted PER2 mRNA cycling, but did not cause significant shifts in cellular localization or binding with CLOCK. Conserved variants were further tested in Drosophila, which confirmed variant-dependent effects on behavioral rhythms. Remarkably, flies expressing variant cycle, the ortholog of BMAL1, also demonstrated deficits in short- and long-term memory, reminiscent of the highly prevalent developmental delay observed in our cohort. We suggest that ultrarare variants in the BMAL1 core clock gene contribute to a neurodevelopmental disorder.

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5. Duncan A, Tadevich L. The role of family quality of life in the caregivers of autistic adolescents receiving treatment for daily living skills. Res Autism;2025 (Sep);127

Adolescence may be a particularly challenging time for autistic teens and their caregivers. Thus, the current study sought to better understand Family Quality of Life (FQOL) in this population. Further, given the impact that daily living skills (DLS) have on the family system, the current study examined whether a DLS intervention impacted FQOL. Fifty-eight adolescents with autism and their caregivers completed the Surviving and Thriving in the Real World (STRW) intervention and caregivers reported on their FQOL using the Beach Center Family Quality of Life (FQOL Scale). Results revealed that caregivers who participated in the STRW intervention endorsed significant positive changes on the Family Interaction (p = .02) and Parenting (p = .03) subscales and Overall FQOL (p = .02) from baseline to post-treatment. Further, higher Emotional Well-Being at baseline was the only FQOL variable that was related to increased changes in DLS from baseline to post-treatment (r = .29, p = 03). Results suggest that completion of the STRW intervention relates to significant positive changes in FQOL. Further, results suggest that targeting aspects of FQOL, such as emotional well-being, may lead to improved treatment gains in autistic teens.

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6. Ferreira H, Santos S, Martins J, Castelo-Branco M, Gonçalves J. Distinct early development trajectories in Nf1(±) and Tsc2(±) mouse models of autism. J Neurodev Disord;2025 (Jul 26);17(1):42.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, and repetitive behaviors. Males are three times more likely to be diagnosed with ASD than females, and sex-dependent alterations in behavior and communication have been reported both in clinical and animal research. Animal models are useful for understanding ASD-related manifestations and their associated neurobiological mechanisms. However, even though ASD is diagnosed during childhood, relatively few animal studies have focused on neonatal development. METHODS: Here, we performed a detailed analysis of neonatal developmental milestones and maternal separation-induced ultrasonic vocalizations (USVs) in two genetic animal models of ASD, neurofibromatosis type 1 (Nf1(±)) and tuberous sclerosis complex 2 (Tsc2(±)). RESULTS: Nf1(±) and Tsc2(±) mice display strikingly distinct developmental profiles regarding motor, strength, and coordination skills. Nf1(±) mouse pups mostly show genotype-related differences, whereas Tsc2(±) mouse pups mainly present sexual dimorphisms. Furthermore, we found several differences regarding the number of USVs, frequency modulation, and temporal and spectral profile. Importantly, Nf1(±) animals tend to present sex- and genotype-dependent differences earlier than the Tsc2(±) mouse pups, suggesting distinct developmental curves between these two animal models. CONCLUSIONS: This study provides a nuanced understanding of how these two ASD models differ in their developmental trajectories. It underscores the importance of studying sex differences and early-life developmental markers, as these could offer crucial insights into ASD’s progression and neurobiology. The distinct profiles of these models may help guide more targeted therapeutic strategies in the future.

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7. Folz J, Nikić K, Nikolić M, Janowicz V, Koelkebeck K, Kret ME. The role of the body in altered facial emotion perception in autism and social anxiety. Behav Res Ther;2025 (Jul 11);193:104819.

Alterations in the perception of facial emotional expression and their physiological resonance, as well as in accurately sensing bodily states (i.e., interoception) have been reported in both autism and social anxiety. In the current study, we aimed to examine the association between physiological responses, their sensation, and facial emotion perception in individuals on the autism spectrum (N = 40), individuals with social anxiety (N = 27) and neurotypical controls (N = 40). Participants first viewed videos of spontaneous facial expressions (anger, happiness, sadness, fear and neutral) while facial muscle responses (corrugator supercilii and zygomaticus major), indicating facial mimicry, and skin conductance, indicating emotional arousal, were recorded. In a separate task, the same expressions were judged regarding their emotion category, the confidence in the accuracy of this judgment, and the intensity of the observed emotional experience. Compared to controls, individuals with social anxiety showed a stronger link between physiological arousal and the perceived intensity of sadness. Individuals on the autism spectrum showed a relatively weaker link between the mimicry of anger and the intensity at which this expression was perceived. Differences in self-reported interoceptive accuracy also played a role in the latter link, suggesting alterations in integrating embodied emotions in autism.

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8. Güvenilir E, Yilmaz Şükranli Z, Abusalim MRS, Okan Oflamaz A, Doğanyiğit Z, Başaran KE, Dolanbay M, Rassoulzadegan M, Taheri S. Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice. J Vis Exp;2025 (Jul 11)(221)

Hypoxia can occur to varying degrees for different reasons during the perinatal period, affecting development. We aim to examine the consequences of mild to severe neonatal hypoxia in mice, focusing on its potential link to neurodegenerative fetal brain dysfunctions related to autism spectrum disorder (ASD). We induced hypoxia in neonatal mice by delivering them in controlled environments with varying oxygen concentrations. The results showed elevated levels of HIF-1α (a marker of hypoxia) in the cerebral cortex and hippocampus, as well as increased neurodegeneration in these regions. Moreover, we observed altered expression of ASD-related miRNAs (miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p, and miR-499a-5p) in hypoxic groups, consistent with previous results in human and animal models of ASD. These molecular alterations were accompanied by behavioral changes such as decreased movement, speed, social interaction, and repetitive behaviors, as well as an increased tendency to exhibit corner-seeking behavior in mice subjected to hypoxic conditions. Although behavioral and molecular changes were detectable in the 12% O2 group (mild hypoxia), the most pronounced changes were observed in the more severe hypoxia groups, at 10% O2 and 8% O2. Overall, the results suggest that neonatal hypoxia can induce lasting molecular changes associated with neurodegenerative diseases with behavioral consequences. Moreover, even in normal birth, exposure to hypoxia during early development can impair memory and learning. The results highlight the need for early detection and intervention in newborns exposed to hypoxia to prevent long-term neurological problems. miRNA levels are regulated during development, and their modifications in tissues, especially in germ cells, constitute a risk factor for the next generation. The analyses provide a basis for studying the regulatory pathways that affect functional and behavioral changes under hypoxia.

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9. Huzard D, Oliva G, Marias M, Granat C, Soubeyre V, do Nascimento Pereira G, Negm A, Grellier G, Devaux J, Bourinet E, François A. Primary sensory neuron dysfunction underlying mechanical itch hypersensitivity in a Shank3 mouse model of autism. Transl Psychiatry;2025 (Jul 28);15(1):259.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by social deficits, repetitive behaviors and atypical sensory perception. The link between ASD and skin abnormalities, inducing itchiness, has never been investigated in depth. This study explores mechanical itch sensitivity in the Shank3(ΔC/ΔC) mouse model. Key observations include heightened scratching in response to skin deformation and hypersensitivity to mechanical itch (i.e. alloknesis) in Shank3(ΔC/ΔC) mice. In Shank3(ΔC/ΔC) mice, ex vivo electrophysiological experiments revealed that C-fiber low-threshold mechanoreceptors (C-LTMRs) were hyporesponsive and transcriptomic analysis showed a downregulation of TAFA4, a protein secreted by C-LMTRs. Interestingly, pharmacologically inhibiting Aβ-LTMR, important in mechanical itch initiation, abolished the itch hypersensitivity. Also, TAFA4 injections reduced the spontaneous scratching response to skin deformation but failed to restore itch sensitivity. Our data suggest that somatosensory deficits in Shank3(ΔC/ΔC) mice lead to a hypersensitivity to itchiness and indicate that two pathways might be regulating mechanical itchiness, dependent or not on TAFA4.

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10. Ismael HM, Ismail PA. Investigating Oxidative Stress and Impaired DNA Repair Capacity as Diagnostic Biomarkers in Autism Spectrum Disorder. J Mol Neurosci;2025 (Jul 28);75(3):93.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by early-onset social communication deficits, restricted/repetitive behaviors, and sensory sensitivities. Although ASD is predominantly influenced by genetic factors, accumulating evidence implicates oxidative stress as a contributing mechanism in its pathophysiology. This study included a total of 89 children, of whom 60 were diagnosed with ASD and 29 were healthy controls. The severity of autism was assessed according to the criteria established in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The study measured the levels of 8-hydroxydeoxyguanosine (8-OHdG), 8-oxoguanine DNA glycosylase 1 (OGG1), 3-nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) using the sandwich ELISA method. The results demonstrate a significant elevation of 8-OHdG in the ASD group compared to the control group (p = 0.043), which positively correlated with ASD symptom severity (p = 0.029). Conversely, OGG1 levels were significantly reduced in ASD (p = 0.0004) and were strongly linked to more severe ASD symptoms (p = 0.0001). Moreover, both 3-NT (p = 0.0005) and AOPP (p = 0.043) levels were significantly elevated in ASD and showed positive correlations with ASD severity (p = 0.0043 and p = 0.046, respectively). The present findings demonstrate marked elevation in oxidative DNA damage, evidenced by increased levels of 8-OHdG and decreased concentrations of OGG1, as well as enhanced protein oxidation, reflected by heightened 3-NT and AOPP levels, in children diagnosed with ASD. The strong correlations observed between elevated oxidative stress biomarkers, diminished OGG1 levels, and increased ASD severity underscore their utility as potential indicators of disease severity and provide key mechanistic insights into ASD pathophysiology.

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11. Jiao JP, Zhang HW, Zhou XZ, Tian SJ, Gao L, Li BM, Luo JX, Wang J, Lan S, Li B, Liao WP. Missense variants in SLC9A6 cause partial epilepsy without neurodevelopmental delay. Orphanet J Rare Dis;2025 (Jul 28);20(1):380.

BACKGROUND: The SLC9A6 gene encodes a monovalent sodium-selective sodium/hydrogen exchanger that is essential in regulating endosomal PH and volume. SLC9A6 variants are associated with Christianson Syndrome, a severe neurodevelopmental disorder that is accompanied by seizures. It is unknown whether SLC9A6 variants are associated with milder phenotypes. METHOD: Trio-based whole-exome sequencing was performed in unrelated cases (families) with epilepsy without acquired causes. Previously reported SLC9A6 variants were reviewed to analyze the mechanism underlying phenotype variations. RESULTS: Five hemizygous variants, including three null and two missense variants, were identified in five males. All the variants were absent in the gnomAD-all populations and the missense variants were predicted to be damaging by multiple in silico tools. The three patients with null variants presented with refractory epilepsies and severe developmental delay; one patient with missense variant in the transmembrane region showed refractory epilepsies and speech delay; and one patient harboring missense variant located in the loop region achieved seizure-free with favorable outcome. Further analysis revealed that the proportions of brain atrophy, microcephaly, and movement disorders in patients with missense variants were significantly lower than that of patients with null variants, suggesting a genotype-phenotype correlation. Additionally, previously reported missense variants in the pore/transmembrane region led to Christianson Syndrome, whereas variants outside these regions were associated with milder phenotype, suggesting a sub-regional effect. CONCLUSION: Missense variants in SLC9A6 are associated with mild partial epilepsies. The genotype-phenotype correlation and molecular sub-regional effect of SLC9A6 help in explaining the mechanisms underlying phenotypic variations.

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12. Mimura Y, Nakajima S, Takano M, Wada M, Taniguchi K, Honda S, Uchida H, Mimura M, Noda Y. Long-interval intracortical inhibition in individuals with autism spectrum disorders: A TMS-EEG study with source estimation analyses. Clin Neurophysiol;2025 (Jul 18);178:2110936.

OBJECTIVE: This study aimed to evaluate Long-interval Intracortical Inhibition (LICI) in the Dorsolateral Prefrontal Cortex (DLPFC) of individuals with Autism Spectrum Disorder (ASD) using transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) with source-based estimation analyses. METHODS: We applied the LICI paradigm to the left DLPFC of 32 individuals with ASD and 34 healthy controls. First, sensor-level Local Mean Field Power (LMFP) was calculated from TMS-evoked potentials for all participants to detect the LICI effect. Subsequently, source-based analyses were performed using dynamic statistical parametric mapping to minimize the influence of volume conduction. Finally, time-frequency (TF) analyses at the source level were conducted to further characterize the LICI effects. RESULTS: LMFP analysis revealed that cortical activity in the interval of 165-234 ms post-stimulation was suppressed by LICI (p = 0.024). Source-based analyses confirmed inhibitory effects within the same time range. Additionally, TF analyses indicated suppressive effects within 30-300 ms in the theta to alpha bands. However, no significant group differences in the LICI effects were detected. CONCLUSIONS: TMS-EEG combined with LICI alone may be insufficient to detect GABA(B) receptor dysfunction in ASD. SIGNIFICANCE: This is the first TMS-EEG study to elucidate the LICI effect by applying source-estimation methods in ASD.

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13. Rea CJ, Lesch K, Hernandez B, Sprecher E, Hauptman M, Epee-Bounya A, Wilson K, Shah SN. Child and Family Characteristics Associated With Age of Autism Spectrum Disorder Diagnosis in a Primary Care Population. J Dev Behav Pediatr;2025 (Jul 28)

OBJECTIVE: To compare a sample of pediatric primary care patients diagnosed with autism spectrum disorder (ASD) with the general clinic population, as well as associations of child and caregiver characteristics with age of diagnosis. METHOD: Cross-sectional data for patients from 2 large, urban primary care practices diagnosed with ASD between March 1, 2018, and February 28, 2022, were collected from the medical record through extraction and chart review. The sample was compared with the total primary care population using χ2 analysis. Unadjusted bivariate linear regression and multivariate linear regression were used to evaluate associations of each variable with age of diagnosis. RESULTS: Patients diagnosed with ASD were more likely to be male, Hispanic, publicly insured and medically complex than the general clinic population. There was also a higher maternal education level in the autism group. In unadjusted linear regression analyses, language delay, connection with Early Intervention (EI), earlier age of parental concern, earlier age of referral, having an M-CHAT completed, higher M-CHAT scores, and having a first-degree relative with ASD were associated with earlier age of diagnosis. In multivariate linear regression analysis, connection with EI, better continuity of care, higher M-CHAT scores and having commercial insurance were associated with earlier diagnosis. Race/ethnicity, language, and Social Vulnerability Index ≥ 90%ile were not significantly associated with age of ASD diagnosis. CONCLUSION: This study reflects shifting prevalence patterns of ASD, but a persistent disparity in age of diagnosis among publicly insured children. It highlights the importance of developmental monitoring, continuity of care, and navigation support to help families obtain ASD diagnoses promptly.

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14. Rostollan MA, Pulliam EH, Scott AL. Caregiver’s Perspectives on Disclosing the Diagnosis of Autism Spectrum Disorder to Their Children. J Dev Behav Pediatr;2025 (Jul 28)

OBJECTIVE: There is growing literature emphasizing the importance of early and tailored parental disclosure of an autism diagnosis to their children. While there are barriers to disclosure, most parents agree that children have a right to know of their diagnosis, with early disclosure being associated with a better quality of life and self-image. Within the literature, however, there is scarcity of populations from the United States represented in qualitative disclosure studies. With the impact of culture and location on language, this study aims to address this gap. METHOD: Caregivers of children with prior diagnosis of ASD (n = 16) were recruited to participate in semistructured interviews. Blinded transcripts of interviews were used to individually create codes that were formed into themes based on consensus of the researchers through thematic analysis. RESULTS: Of the 16 caregivers interviewed, 14 were White and all 16 were female. Twelve caregivers reported working or volunteering in areas with high exposure to the autism community. Thematic analysis yielded 4 themes relating to diagnosis disclosure: (1) Language of Disclosure, (2) Disclosure as a Journey, (3) Purpose of Disclosure, and (4) Process of Disclosure. CONCLUSION: This exploratory, qualitative study examines caregiver’s perspectives on the disclosure process, strengthening the consensus with emerging literature surrounding the process of disclosure and highlighting the role language plays in the disclosure process. More specifically, the metaphors used by parents to describe autism change from generally positive euphemisms to more well-balanced and realistic metaphors that encapsulate both triumphs and struggles that accompany an autism diagnosis.

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15. Stahmer AC, Brookman-Frazee L. Bridging the Leadership Gap in Autism Care: A Global Imperative for Effective Implementation-Authors Reply. J Am Acad Child Adolesc Psychiatry;2025 (Jul 22)

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16. Toman AK, AbdulRasool HR, Lami F, Jasim SM, Jaber OA, Nayeri ND, Sabet MS, Al-Gburi G. Exploring co-occurring conditions in Iraqi children with autism spectrum disorder: prevalence, characteristics, and potential risk factors. Front Psychiatry;2025;16:1592374.

INTRODUCTION: Co-occurring conditions are common in children with autism spectrum disorder (ASD) and have important negative impacts on the children and their families. For Iraqi children, local healthcare systems tend to place more emphasis on the management of ASD itself while neglecting co-occurring conditions. OBJECTIVES: This study aims to investigate the prevalence, characteristics, and potential risk factors of co-occurring epilepsy, sleep, and weight issues among Iraqi children with ASD. METHODS: A multicenter cross-sectional study was conducted from January 24 to August 7, 2024, including children from Imam Hussein Centre, Al-Subtain Academy for Autism and Neurodevelopmental Disorders, and Baghdad’s National Centre for Autism and Child Psychiatry. A structured questionnaire was used, including 35 items for demographic information, epilepsy, sleep problems, and weight issues. RESULTS: Our sample included 240 children, of whom 34 (14.2%) had co-occurring epilepsy, 178 (74.2%) had at least one sleep problem, and 104 (43.3%) were obese. Among children with epilepsy, 18 (52.9%) received their diagnosis before ASD. The most prescribed anticonvulsant, sodium valproate, was noted in 18 (52.9%) cases. Difficulty falling asleep was the most common sleep problem, affecting 97 (40.4%), while sleepwalking was reported in only 26 (10.8%). Significant differences in the body-mass index were observed based on risperidone use (adjusted p-value = 0.036, R-value = 0.163, 95% CI: 0.031, 0.288), sleep duration (r = -0.166, adjusted p-value = 0.036), and diet (adjusted p-value = 0.036, ϵ(2) = 0.038, 95% CI: 0.005, 0.087). However, no significant association was demonstrated between BMI and screen time (adjusted p-value = 0.264). CONCLUSION: Co-occurring conditions are common among children with ASD and should be assessed simultaneously. Additionally, since some of the children might be diagnosed with epilepsy first, it is important to consider co-occurring ASD in their diagnosis.

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17. Trottier-Dumont W, Bussières EL, Deneault AA, Madigan S, Cyr C. Attachment in autistic children as measured with the strange situation procedure: a systematic review and a meta-analysis. Attach Hum Dev;2025 (Jul 28):1-23.

Since the inception of attachment theory, parent-child relationships has been examined in different populations, including autistic children. Attachment in autistic children has been measured using inconsistent separation-reunion procedures, making it difficult to examine whether autistic children are more or less likely to develop a secure attachment compared to non-autistic children. This study aims to meta-analyze data from studies that have assessed attachment in autistic children using a standardized version of the Strange Situation Procedure. Using the CASCADE catalogue, we identified six studies (n = 202). Results revealed that 45.6% were classified as secure, 18.7% as avoidant, 8.5% as resistant, and 27.2% as disorganized, which was statistically similar to the proportions of attachment categories in general population. Moderator analyses revealed a higher proportion of secure attachment among older children and more recently published studies. Future research should focus on unifying methodological approaches to studying attachment in autistic children.

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18. Wang Y, Wang Y, Zhu Z, Xia Z, Wang N, Li M, Jiao Z, Pan N, Zhang Y, Chen Q, Ke X, Zhang W. Fundus Peripapillary Vascular Changes in Autism Spectrum Disorder: A Cross-Sectional Study. Autism Res;2025 (Jul 28)

In this cross-sectional study, participants were recruited through convenience sampling from the Children’s Mental Health Research Center at The Affiliated Brain Hospital of Nanjing Medical University and the Department of Ophthalmology at The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, between December 2019 and October 2024. A total of 200 eyes were ultimately enrolled in this study, sourced from 53 individuals with ASD, aged between 7 and 13 years, and an equal number of age- and sex-matched neurotypical (NT) controls. The aim of this research is to explore the changes in retinal and choroidal vasculature in children with ASD, evaluated through optical coherence tomography and its angiography, and to further investigate the potential value of retinal vascular characteristics in the auxiliary screening and diagnosis of ASD. We analyzed intergroup differences in perfusion density (PD), vessel density, flux index (FI), fractal dimension (FD), and vessel diameter (Dm) in the peripapillary region, further stratified by subquadrants and vessel types. The results show that ASD children exhibited significant differences compared to neurotypical controls, including increased PD and Dm in the supero-nasal quadrant (p < 0.01), changes in capillary FI in the nasal quadrant (p = 0.008), increased venous FD (p = 0.009), and abnormal choroidal FI in the temporal quadrant (p = 0.008). A random forest classification model constructed based on these key features demonstrated promising performance (AUC = 0.7853) in distinguishing ASD from NT individuals, highlighting the potential of retinal vascular characteristics for auxiliary ASD screening. Moreover, retinal vascular parameters were significantly correlated (p < 0.01) with blood oxygen level-dependent signals from functional magnetic resonance imaging in several brain regions, such as the amygdala (p = 0.004-0.009) and temporal lobe (p = 0.000-0.009). Further stepwise regression analysis indicates that key retinal vascular characteristics could partially predict core clinical features of ASD, such as social functioning (adjusted R(2) = 0.091-0.104, quantified by total and subscale scores of Social Responsiveness Scale) and cognitive ability (adjusted R(2) = 0.2785, quantified by total intelligence quotient scores). This study underscores the potential of retinal vascular features as biomarkers for ASD and provides a basis for future research on non-invasive retinal imaging-based approaches for ASD screening and diagnosis, while offering new perspectives for understanding the pathological mechanisms and clinical applications of ASD.

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19. Widiastuti AA, Atmoko A, Eva N, Ervina I, Leylasari HT, Rustam HK, Juraidin I. Bridging the Leadership Gap in Autism Care: A Global Imperative for Effective Implementation. J Am Acad Child Adolesc Psychiatry;2025 (Jul 22)

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20. Wong OW, Sm Chan S, Chau SW, Chu WC, Ho CS, Ho SW, Hung SF, Hussain S, Lai KY, Lam AM, Lo HH, Ma KK, Ma SL, Mo FY, Sham PC, Shea CK, So SH, Tsoi KK, Leung PW. Autism epidemiology in Hong Kong children and youths aged 6-17: Implications on autism screening and sex differences in the community. Autism;2025 (Jul 27):13623613251360269.

Epidemiological studies on autism lack representation from Asia. We estimated the prevalence of autism among children and youths in Hong Kong using a two-stage approach. In addition, we evaluated the psychometric properties of the screening instrument and explored sex differences within an epidemiological context. A random school-based sample of 5,865 children and youths were screened with the Autism Spectrum Quotient-10 (AQ-10). Then, a subsample of 317 participants underwent the Autism Diagnostic Interview-Revised assessment. Prevalence was estimated by applying positive and negative predictive values (PPV/NPV) of AQ-10 derived from the subsample to the entire cohort. None of the screened negative participants had autism, resulting in an NPV of 100%. Discrepant PPVs were noted for males (20.4%) and females (5.20%). The estimated prevalence was 2.57% using sex-specific PPVs. Explorative analysis on AQ-10 Positive participants without the diagnosis (i.e. ‘false positives’) showed significantly elevated autistic symptoms. The prevalence of autism in Hong Kong is comparable to the recent estimates in Western countries, which poses a significant public health challenge. Despite the high false-positive rates, AQ-10 remains valuable for excluding autism and identifying those with autistic symptoms. Furthermore, community-based studies are crucial to address sex differences in autism expression.Lay abstractAlthough studies have found that autism is becoming more common, little is known whether this is true in Asian countries. This study looked into how many children and teenagers in Hong Kong might have autism. We first screened 5,865 school-aged children and youths with the Autism Spectrum Quotient-10 (AQ-10). Then, we conducted in-depth interviews with 317 of them to assess for autism. We found that around 2.57% of children and youths aged 6-17 years in Hong Kong might have autism. This number is similar to that of the Western countries. Furthermore, we also discovered that boys who were screened positive on the AQ-10 were more likely to have autism than girls. This could be because autism is more common in boys, and the AQ-10 might be better at spotting autism in boys than in girls. In the future, studies will need to find an optimal way of detecting autism in the community, considering how autism may present differently in boys and girls.

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21. Xu W, Li H, Li J, Jin M. Age of machine learning: new trends in autism spectrum disorder prediction. Front Microbiol;2025;16:1492484.

In recent years, there has been an increase in the incidence of autism spectrum disorder (ASD), its pathogenesis remains unknown, and there are no effective treatments available. Early identification of individuals at risk enables early targeted intervention, which improves outcomes. Through the integration of artificial intelligence and the medical field, researchers can establish a machine learning (ML) risk prediction model to estimate the risk of ASD. Currently, a variety of risk models have been developed using multiple factors, such as genetic background, gaze behavior, adverse conditions during pregnancy and childbirth, magnetic resonance imaging of the brain, and intestinal microbial composition, to predict ASD. These ML prediction models have shown some reliability in predicting ASD risk. In the future, ML prediction models for ASD will present significant challenges and opportunities, potentially helping identify drug targets for developing novel therapies to alleviate ASD symptoms and enable precision medicine.

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22. Yu L, Sun L, Yue X, Wang Y, Chen C. Differences between Autism spectrum disorders and attention-deficit/hyperactivity disorder in brain function: A resting-state fMRI research. Res Dev Disabil;2025 (Jul 25);164:105081.

OBJECTIVE: The clinical distinction between ASD and ADHD poses significant diagnostic challenges due to their symptomatic similarities. To address this issue, we systematically examined functional brain differences between these disorders. METHODS: By combining amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) resting-state fMRI metrics, this study provides a more robust neurofunctional characterization of ASD and ADHD. Using resting-state fMRI, we compared ALFF and ReHo among four groups: 28 ASD-only participants, 29 typically developing controls matched to ASD participants (TD(ASD)), 28 ADHD-only participants, 30 typically developing controls matched to ADHD participants (TD(ADHD)). These analyses quantified region-specific neural activity intensity and local synchronization to identify disorder-specific functional patterns. RESULTS: Compared to TD(ASD) controls, the ASD group exhibited significantly elevated ALFF and ReHo in the anterior cingulate gyrus (ACG) and right precentral gyrus (PreCG) (p < 0.05, GRF-corrected). In contrast, no significant differences were observed between ADHD and TD(ADHD) groups. Direct ASD-ADHD comparisons revealed: Increased ALFF in the right PreCG and decreased ALFF in the left fusiform gyrus (FG); Elevated ReHo in the right middle occipital gyrus (MOG) in ASD (p < 0.05, GRF-corrected). CONCLUSION: The distinct ALFF and ReHo patterns observed between ASD and ADHD provide compelling neurobiological evidence for their divergent neural mechanisms. These disorder-specific functional signatures, particularly in the anterior cingulate and occipito-frontal circuits, may guide future neuromodulation research and eventually contribute to refining differential diagnostic frameworks in clinical practice.

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23. Zhan X, Kuang Z, Wang Y, Li X, Zeng Y, Zhong Y. Health benefits of adapted physical activity for children and adolescents with autism Using the ICF-CY framework: A scoping review. Dev Neurorehabil;2025 (Jul 27):1-14.

PURPOSE: The aim of this study was to conduct a scoping review of the health benefits of adapted physical activity (APA) programs for children and adolescents with autism based on the ICF-CY. METHODS: Retrieving experimental studies related to APA in children and adolescents (0-18 years) with autism in the PubMed, Web of Science, EBSCO, PsycINFO, and CNKI databases, January 2014-December 2023. RESULTS: A total of 34 studies were included (involving 13 countries and 997 subjects). Coding of health effects according to ICF-CY categories, 52% of the 210 outcome items focused on body functions, 48% on activities and participation. CONCLUSIONS: With its individualized, diversified and structured characteristics, APA not only serves as an effective non-pharmacological treatment strategy, but also an important way to promote the health of children and adolescents with autism in all-round way. However, the complexity of environmental factors makes it challenging to design an APA program based on the concept of ICF-CY.

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24. Zhang X, Fu C, Wang M, Feng D, Wang H, Li H, Liu X, Zeng L, Li L, Yao P. Brain-derived neurotrophic factor levels and oxidative stress in autism: evidence from children and a mouse model. J Psychiatry Neurosci;2025 (Jul-Aug);50(4):E218-e233.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a key factor in neurodevelopment of autism spectrum disorder (ASD), yet the variability of peripheral BDNF levels in ASD remains debated. We sought to investigate the relationship between circulating oxidative stress and peripheral BDNF in children with ASD. METHODS: We analyzed plasma BDNF levels and redox status in both plasma and peripheral blood mononuclear cells (PBMCs) among children with ASD and typically developing (TD) children aged 2-5 years. We generated an autism-like mouse model via prenatal exposure to medroxyprogesterone acetate (MPA). To modulate circulating redox balance, we employed tyrosine kinase-driven lentiviral expression of superoxide dismutase 2 (Sod2) and hematopoietic stem cell (HSC) transplantation with Sod2 overexpression. We then assessed circulating redox balance, gene expression, epigenetic changes, peripheral BDNF levels, and autism-like behaviours in offspring. RESULTS: We included 78 children in the ASD group and 63 children in the TD group. Children with ASD exhibited elevated plasma BDNF levels and an altered redox balance compared with TD controls. In the mouse model, MPA-exposed autism-like offspring demonstrated increased peripheral BDNF levels and heightened oxidative stress in hematopoietic stem cells, endothelial cells, and PBMCs. Tyrosine kinase-Sod2 lentiviral expression in the endothelium fully normalized peripheral BDNF levels, while HSC transplantation with Sod2 overexpression not only reduced plasma BDNF levels, but also alleviated autism-like behaviours. LIMITATIONS: This study’s cross-sectional data limit causal inference between oxidative stress and BDNF levels among children with ASD. The mouse model, while informative, may not fully recapitulate human ASD heterogeneity. CONCLUSION: In ASD, elevated peripheral BDNF levels are associated with circulating oxidative stress. Prenatal progestin exposure induces both increased peripheral BDNF and oxidative stress, effects that can be completely reversed through SOD2 modulation in circulation among mouse offspring.

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25. Zibaee A, Elyasi F, Fariborzifar A, Shirazi E. Unanticipated Pathological Laughter Following Atomoxetine Administration in a Child With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Neuropsychopharmacol Rep;2025 (Sep);45(3):e70028.

INTRODUCTION: Atomoxetine, a selective norepinephrine reuptake inhibitor (NRI), is commonly prescribed for attention-deficit/hyperactivity disorder (ADHD) and has shown effectiveness in children with autism spectrum disorder (ASD). Although mood disturbances and psychiatric symptoms are recognized side effects, pathological laughter has not been previously reported. CASE PRESENTATION: We present the case of a 6-year-old boy diagnosed with both ASD and ADHD who developed sudden, uncontrollable episodes of pathological laughter after beginning low-dose atomoxetine (5 mg/day, ~0.25 mg/kg). The child had a history of hyperactivity and aggression, managed with risperidone and clonidine. Within 5 days of initiating atomoxetine, he exhibited frequent, spontaneous laughter lasting 2-5 min without any apparent emotional trigger. These episodes resolved within 10 days despite continued atomoxetine treatment, coinciding with a minor increase in risperidone dosage. Following this period, the child displayed noticeable improvements in attention, eye contact, and overall cooperation. Atomoxetine was later increased to 10 mg/day, with no recurrence of pathological laughter. CONCLUSION: This case suggests that pathological laughter may be a rare but temporary side effect of atomoxetine, even at low doses. Given the child’s familial history of bipolar disorder and the influence of catecholamines on mood regulation, clinicians should be vigilant in monitoring mood-related side effects in children with neurodevelopmental disorders. This report emphasizes the need for personalized treatment approaches and further investigation into the mechanisms and risk factors underlying this phenomenon.

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