1. Almughyiri S. Influence of bronfenbrenner ecological theory on career choices of preservice teachers of students with developmental disabilities. Sci Rep. 2025; 15(1): 29023.

Objectives The current study explored how ecological systems influence Saudi Arabian preservice male special education teachers’ career choice and professional development. Guided by Ecological Systems Theory, the study examined how individual, family, institution, and culture influence their attitudes. Methods The qualitative phenomenological research approach was followed, including semi-structured interviews with five preservice teachers who belonged to Riyadh-based universities. Results Three dominant themes were elicited: (1) the role of family, community, religious, and cultural values – Islamic values and family encouragement were cited by participants as key motivators; (2) negative interaction with teachers throughout the educational journey, wherein participants characterized the heavily lecturing teaching style as demotivating; and (3) the general impact of faculty interactions, with both positive aspects (e.g., availability of instructors) and limitations posed by the absence of local contextual knowledge portrayed by some members of the faculty. Conclusions The results highlight the need to recognize the complex ecological environment of teacher education programs, paying special attention to the contribution of religion, culture, and meaningful faculty interaction in influencing preservice teachers.

Lien vers le texte intégral (Open Access ou abonnement)

2. Angell AM, Li Y, Bian J, Parchment C, Yin L, Chamala S, Hakimjavadi H, Thompson L, Guo Y. Algorithmic Fairness in Machine Learning Prediction of Autism Using Electronic Health Records. Stud Health Technol Inform. 2025; 329: 1180-4.

Efforts to improve early diagnosis of autism spectrum disorder (ASD) in children are beginning to use machine learning (ML) approaches applied to real-world clinical datasets, such as electronic health records (EHRs). However, sex-based disparities in ASD diagnosis highlight the need for fair prediction models that ensure equitable performance across demographic groups for ASD identification. This retrospective case-control study aimed to develop ML-based prediction models for ASD diagnosis using risk factors found in EHRs and assess their algorithmic fairness. The study cohorts included 70,803 children diagnosed with ASD and 212,409 matched controls without ASD. We built logistic regression and Xgboost models and evaluated their performance using standard metrics, including accuracy, recall, precision, F1-score, and area under the curve (AUC). To assess fairness, we examined model performance by sex and calculated fairness-specific metrics, such as equal opportunity (recall parity) and equalized odds, to identify potential biases in model predictions between boys and girls. Our results revealed significant fairness issues in ML models for ASD prediction using EHRs.

Lien vers le texte intégral (Open Access ou abonnement)

3. Beckwith R, Stephens-Lewis D. « There’s no one-size-fits-all kind of solution »: An interpretative phenomenological analysis of the experiences of autistic individuals living with Ehlers-Danlos syndrome. Res Dev Disabil. 2025; 164: 105084.

OBJECTIVE: Approximately a third of individuals live with multiple health conditions and this number is rising. Research suggests that living with a chronic condition can profoundly impact upon one’s life and identity, however little attention has been paid to the experiences of those with multiple conditions. Ehlers-Danlos syndrome (EDS) is a rarely-diagnosed connective tissue disorder causing extensive debilitating symptoms and while these symptoms are primarily physical, EDS often co-occurs with autism. This study sought to gain insight into the experience of autistic individuals living with EDS and thus investigate how illness identity occurs with multiple conditions. DESIGN: Interpretative Phenomenological Analysis (IPA) was used. METHODS: Semi-structured interviews were conducted with four autistic women living with EDS. RESULTS: Analysis resulted in three superordinate themes, consisting of ‘Transformation,’ ‘Making sense,’ and ‘The negatives.’ While interrelated, these themes capture the ways in which the conditions have changed the participants’ lives, both positively and negatively. Furthermore, they capture how the participants make sense and create meaning in their new identities. CONCLUSION: Individuals living with co-occurring conditions have multiple illness identities which affect their overall sense of self. Within this study, participants incorporated both conditions into their new identities, although the extent to which they rejected or accepted these conditions varied individually based on numerous biopsychosocial factors, which shifted continually, including healthcare professionals’ attitudes and awareness of conditions, stigma, finding community and symptom severity. Thus, illness identity is in a constant state of flux. These findings highlight the need for more individualised, supportive care for autistic individuals living with EDS.

Lien vers le texte intégral (Open Access ou abonnement)

4. Ben-Arie G, Shelef I, Meiri G, Menashe I, Dinstein I, Arazi A. Benign External Hydrocephalus in a Subgroup of Autistic Children Prior to Autism Diagnosis. Autism Res. 2025.

Benign external hydrocephalus (BEH) is evident in < 0.6% of births. It is defined by abnormally large cerebrospinal fluid (CSF) volumes in the subarachnoid space (SAS) and otherwise normal neuroimaging findings before 2 years of age. BEH has not been associated with specific developmental disorders and is not treated because it usually resolves spontaneously. However, quantitative MRI studies have reported that some toddlers with autism exhibit enlarged extra-axial CSF (EA-CSF) volumes. Our objective was to determine whether a subgroup of children with autism exhibits both qualitative BEH and quantitative EA-CSF volume enlargements. We analyzed clinical brain MRI scans in a retrospective sample of 136 children, 5-99 months old, 83 with autism, who were assessed for BEH by neuroradiologists. EA-CSF volume and total cerebral volume (TCV) were quantified in T2-weighted scans by manual labeling. Measures were compared across groups while stratifying participants by age. Neuroradiologists reported BEH findings in 33% of autistic children scanned before the age of 2 years old (i.e., before autism diagnosis). Quantitative MRI analyses demonstrated that autistic children in this age group exhibited significantly larger EA-CSF volumes relative to controls (t((49)) = 2.89, p = 0.006, Cohen's d = 0.82) with 30% of autistic children and 9.5% of the controls exhibiting EA-CSF/TCV ratios > 0.14, a previously suggested threshold of potential clinical relevance. EA-CSF differences were not apparent in older children. The prevalence of BEH associated with quantifiable EA-CSF enlargements was remarkably high in toddlers who later developed autism, suggesting a specific autism etiology involving early transient CSF circulation problems with potentially long-lasting neurodevelopmental impact.

Lien vers le texte intégral (Open Access ou abonnement)

5. Blanchard A, Chihuri S, Ing C, DiGuiseppi C, Li G. Association between autism spectrum disorder and intentional self-harm. Inj Epidemiol. 2025; 12(1): 47.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent challenges in communication and social interaction and, often accompanied by restricted and repetitive patterns of behavior and interests. The reported prevalence of ASD in the United States has tripled in the past two decades. Recent studies indicate that ASD is associated with increased self-injurious behaviors. The purpose of this study is to assess the excess risk of intentional self-harm associated with ASD. METHODS: Using a repeated cross-sectional study design, we analyzed data from the 2016-2020 Nationwide Emergency Department Samples (NEDS), the largest all-payer emergency department (ED) database in the United States. ED visits for intentional self-harm were identified using the ICD-10-CM external cause-of-injury matrix. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ED-treated intentional self-harm associated with ASD in the presence or absence of co-occurring attention-deficit hyperactivity disorder (ADHD) and/or intellectual disability (ID) were estimated through multivariable logistic regression. RESULTS: The 2016-2020 NEDS recorded an unweighted total of 159,590,866 ED visits, of which 2,570,446 (1.6%) were related to intentional self-harm. Using weighted data, intentional self-injury accounted for 2.3% of ED visits made by patients with a diagnosis of ASD, 3.9% of ED visits by patients with a diagnosis of ADHD, and 3.3% of ED visits by patients with a diagnosis of ID. Compared to patients without ASD or ADHD/ID, patients with ASD alone had a 65% increased odds of intentional self-harm (aOR = 1.65; 95% CI: 1.60, 1.70); in addition, patients with ADHD/ID but no ASD a 186% increased odds (aOR = 2.86; 95% CI: 2.83, 2.88), and patients with both ASD and ADHD/ ID a 170% increased odds (aOR = 2.70; 95% CI: 2.58, 2.82) of intentional self-harm. Poisoning accounted for 82.3% of the intentional self-harm-related ED visits among patients without ASD and 61.0% of intentional self-harm-related ED visits among patients with ASD. CONCLUSIONS: ASD is associated with a significantly increased risk of ED-treated intentional self-harm, particularly in patients with co-occurring ADHD or ID. Poisoning from psychotropic and other pharmaceutical drugs is the leading mechanism of intentional self-harm.

Lien vers le texte intégral (Open Access ou abonnement)

6. Burrows CA, Sung S, Zheng S, Young GS, Charman T, Klaiman C, Klin A, Marrus N, Ozonoff S, Piven J, Robins DL, Schmidt RJ, Schwichtenberg AJ, Webb SJ, Zwaigenbaum L, Carver LJ, Chawarska K, Curtin S, Jeste SS, Iverson JM, Landa RJ, Messinger DS, Roberts JE, Stone WL, Tager-Flusberg H, Esler AN, Miller M, Bishop SL, Elison JT. Sex-Related Measurement Bias in Autism Spectrum Disorder Symptoms in the Baby Siblings Research Consortium. JAMA Netw Open. 2025; 8(8): e2525887.

IMPORTANCE: Disparities exist in age of diagnosis and prevalence of autism spectrum disorder (ASD) for female compared with male children. Correcting for sources of bias is critical for improving equitable ASD identification. OBJECTIVE: To determine whether sex differences exist in measurement of ASD symptoms using the Autism Diagnostic Observation Schedule (ADOS) among young children at high familial likelihood (HFL) and low familial likelihood (LFL) of ASD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study collected longitudinal, prospective data from the Baby Siblings Research Consortium between January 1, 2003, and December 31, 2021. Participants included 3106 children who had an older sibling with ASD (HFL group) and 1444 without (LFL group). Data from as many as 3 visits when participants were aged 20 to 40 months were included. Analysis occurred between March 1, 2023, and May 29, 2025. EXPOSURES: Child sex and age and ASD diagnosis. MAIN OUTCOMES AND MEASURES: Measurement invariance by sex and age was examined across item-level ADOS data. Diagnostic group and sex differences were then examined using mixed-effect models on corrected scores. RESULTS: Repeated visits (n = 7557) from 4550 participants (2548 [56.0%] male) were included, of whom 1444 (31.7%) were in the LFL and 3016 (68.3%) in the HFL groups. Confirmatory factor analysis indicated social communication and restricted and repetitive behaviors models fit the data well in the HFL group but poorly in the LFL group. In the HFL group, females were rated as less impaired in eye contact (differential item functioning estimate [SE] = 0.088 [0.033]; P = .01), and their response to joint attention (differential item functioning estimate [SE] = 0.290 [0.105]; P = .01) and quality of social overtures (differential item functioning estimate [SE] = 0.053 [0.019]; P = .005) was associated with less underlying social communication difficulties compared with males. Adjusting for differential item functioning by age and sex resulted in moderate levels of measurement differences. Females showed milder autistic traits than males, although this gap was smaller in the participants diagnosed with ASD. CONCLUSIONS AND RELEVANCE: Sex differences exist in the general population in many social communication traits, yet ASD diagnostic thresholds do not account for these sex differences. Future instrument development, as well as clinician training, should acknowledge milder presentation (fewer difficulties with eye contact or quality of social impairments) in many females. This may help identify developmental differences earlier and improve outcomes for autistic females (estimate [SE] = -0.160 [0.061]; P = .009).

Lien vers le texte intégral (Open Access ou abonnement)

7. Cox G, Katz SL, Bijelić V, Barrowman N, Barwell T, Shamsi R, Blinder H, Cleroux M, Brunet M, Remedios J, Johansen T, Dussah N, Ersu R. Home video clips compared to polygraphy for obstructive sleep apnea diagnosis in children with autism spectrum disorder: A pilot study. Sleep Med. 2025; 134: 106737.

INTRODUCTION: Children with autism spectrum disorder (ASD) have higher prevalence of obstructive sleep apnea (OSA) than typically developing children. Polysomnography (PSG), the gold standard test is challenging for children with ASD. Polygraphy (PG) may be better tolerated, but more accessible screening tools are needed. We evaluated diagnostic characteristics of video clips for OSA in this pilot study. METHODS: Children 4-18 years with ASD referred for PSG for suspected OSA were recruited. Parents recorded 3 2-min home videos, scored for OSA presence using Monash score (MS, positive if ≥ 3). Participants completed the Pediatric Sleep Questionnaire (PSQ; positive if ≥ 0.33) and underwent home PG, scored by obstructive apnea hypopnea index (oAHI), oxygen desaturation index 3 % (ODI3; ≥4.3 and > 7 thresholds) and McGill Oximetry Score (MOS; positive if ≥ 2). Receiver-operator curves were used to compare diagnostic performance across tools for moderate-severe OSA (oAHI ≥5 events/hour). RESULTS: 26 children participated; 15 (median age 7.1) provided video clips. Median oAHI was 2.4/hr; 26.7 % had moderate-severe OSA. Fourteen (93.3 %) had PSQ ≥0.33, three had MOS ≥2. ODI3 was ≥4.3 in 7 and > 7 in 6 children. Median MS was 3.0. MS had 100 % sensitivity, 63.6 % specificity and AUC 78.4 for detecting moderate-severe OSA; average AUC increased when MS was combined with oximetry metrics. CONCLUSION: MS showed high sensitivity but low specificity in detecting moderate-severe OSA. MS outperformed PSQ and MOS, but not ODI3. MS may be a viable alternative screening tool to identify OSA in children with ASD but requires further validation.

Lien vers le texte intégral (Open Access ou abonnement)

8. Duncan A, Meinzen-Derr J, Ruble L, Fassler C, Stark LJ. Closing the Gap: A Randomized Trial Targeting Daily Living Skills in Autistic Adolescents. Focus Autism Other Dev Disabl. 2025.

Autistic adolescents without an intellectual disability (ID) have daily living skills (DLS) that are approximately 6 years below peers. This study evaluated the efficacy of the Surviving and Thriving in the Real World (STRW) intervention, which targets DLS, compared to an active control group. Autistic adolescents were randomized to STRW or control. The primary outcome was the caregiver-reported Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3) DLS domain and Personal, Domestic, and Community sub-domains. The secondary outcome was DLS Goal Attainment Scaling (DLS-GAS) caregiver interview. Compared to control (n = 22), autistic teens in STRW (n = 26) made significant improvements on the VABS-3 DLS domain (p = .04) and Domestic sub-domain (p = .01) and the DLS-GAS areas of Cooking, Laundry, and Money Management (all p’s < .05). STRW narrowed the gap between DLS and age as autistic adolescents acquired age-appropriate domestic, personal, and community DLS compared to the control group.

Lien vers le texte intégral (Open Access ou abonnement)

9. Fatemi SH, Folsom TD, Eschenlauer A, Chekouo T. Impaired Aggrephagy, Interrupted Vesicular Trafficking, and Cellular Stress, Lead to Protein Aggregation, and Synaptic Dysfunction in Cerebellum of Children and Adults with Idiopathic Autism. Cerebellum. 2025; 24(5): 140.

Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with genetic and environmental etiologies involving several brain areas exhibiting abnormalities of cognition and social behavior. Previous work showed involvement of synaptic abnormalities in dorsolateral prefrontal cortex [1]. We hypothesized whether similar synaptic proteins were involved in pathology of cerebellar vermis of children and adults with ASD. Subcellular fractions of synaptosomes from cerebellar vermal cortices of age-, brain area-, and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of proteomic data in cerebellar vermis of children with ASD showed enrichment of significantly downregulated pathways and proteins (FDR-adjusted p < 0.05) involved in protein folding, Rho GTPase cycle, aggrephagy, macroautophagy, anterograde and retrograde transport, proteinopathy, protein stability, and cell response to stress. Enrichment of significantly upregulated pathways and proteins (FDR-adjusted p < 0.05) involved processes of glycolysis, gluconeogenesis, metabolism of amino acids, and degradation of lysine, fatty acids, valine, leucine, and isoleucine. Analysis of proteomic data in cerebellar vermis of adults with ASD showed enrichment of significantly downregulated pathways and proteins (FDR-adjusted p < 0.05) involved in aggrephagy, COPI-mediated anterograde transport and COPI-independent Golgi-to-ER retrograde transport, endocytosis, presynaptic, postsynaptic, and PSD related vesicle mediated activities, serotonin and dopamine neurotransmitter release, and neurodegeneration-related diseases. Enrichment of significantly upregulated pathways and proteins (FDR-adjusted p < 0.05) in adults with ASD included peptide cross-linking, amyloidosis, intermediate filament organization, citrullination, methylation, and proteolysis. Overall, the proteomic data support the concept that cerebellar abnormalities in synaptic structure and function begin during fetal cerebellar development [2], culminate in early childhood, and evolve into adulthood, consistent with pathologic involvement of genes subserving the cognitive domains in ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12311-025-01880-5.

Lien vers le texte intégral (Open Access ou abonnement)

10. Firouzjah MH, Pourazar M, Nazari Kakvandi S, Dalasm RA. The impact of physical activities on physical literacy and cognitive performance of children with autism spectrum disorder (ASD). Early Hum Dev. 2025; 210: 106350.

PURPOSE: Autism spectrum disorder (ASD) is one of the most severe childhood disorders and every child with this disorder has a unique situation in terms of strengths or challenges in cognitive, motor, emotional and social fields. METHODS: This study is semi-experimental with pre-test and post-test design and a control group. The statistical population in this research included all (ASD) from 8 to 12 years old in the educational centers for children with this disorder in Mazandaran province in 2024. Random sampling method was applied to select the target sample, based on which 30 children with autism spectrum disorders were selected for this study. The training program was taken from Horwitz and Sissel (Horwitz R), which includes reinforcement, games, and sports activities for children, performed by the experimental group for 24 sessions (60 min each session and for 70 days). Canadian Assessment of Physical Literacy – Second Edition (CAPL-2) was employed to assess physical literacy and Tower of London test for cognitive performance. The data were analyzed by multivariate covariance method. RESULTS: The obtained results indicated that for the total physical literacy, the results of the post-hoc-test for the main effect of Practice intervention showed that the experimental group is significantly different from control group, all p < 0.05. Means comparisons showed that the experimental group resulted in higher physical literacy than control group. Also time test (reaction time) from the series of tests of the tower of London (Cognitive Performance) no significant differences two groups in the pre-test (F > 1), confirming that the two groups did not differ before training. CONCLUSION: Therefore, it can be concluded that performing physical activities as an essential and main part of the daily schedule of these children can provide effective consequences in improving their cognitive performance and physical literacy.

Lien vers le texte intégral (Open Access ou abonnement)

11. Giani L, Michelini G, Ajmone PF, Scaini S, Allegri B, Costantino A, Vizziello P. Executive function deficits as risk markers for psychopathology and autism related traits in cornelia de lange and rubinstein-Taybi syndromes. J Psychiatr Res. 2025; 190: 181-9.

BACKGROUND AND AIM: There is evidence that executive function (EF) deficits might act as transdiagnostic risk factors for a wide range of psychopathology in typically developmental children. We aim to test the implications of EF deficits on internalizing, externalizing and autistic symptoms in youth with Cornelia de Lange (CdLS) and Rubinstein-Taybi syndromes (RSTS). METHOD: This cross-sectional study was carried out on a sample of 14 patients with CdLS (64 % girls, age = 8.00 ± 4.55) and 15 patients with RSTS (53 % girls, age = 10.27 ± 4.65) recruited through follow-ups. Executive functioning, internalizing and externalizing symptoms, and ASD-related traits were assessed with the Behavior Rating Inventory of Executive Function, the Child Behavior Checklist, and the Social Communication Questionnaire. Stepwise linear regression analyses were performed. RESULTS: Inhibition, set-shifting and planning emerged as the most robust EF predictors of clinically relevant emotional and behavioral difficulties in CdLS and RSTS, as well as of the triads of impairments associated with syndromic autism. CONCLUSION: Being aware of the neuropsychological deficits underneath a broad spectrum of psychological symptoms might foster the setting up of proper rehabilitative programs targeting EF deficits to reduce psychopathology in rare genetic syndromes.

Lien vers le texte intégral (Open Access ou abonnement)

12. Goodman LC, Richard MA, Woodhouse JP, Ihnen SKZ, Capal JK, Northrup H, Krueger DA, Bebin EM, Wu JY, Sahin M, Pearson DA. Developmental Trajectories of Adaptive Functioning and Behavior Problems in Children With Co-Occurring Tuberous Sclerosis Complex and Autism Spectrum Disorder, With and Without Seizures. Pediatr Neurol. 2025; 171: 54-62.

BACKGROUND: Tuberous sclerosis complex (TSC) is associated with higher risk of adaptive problems, behavior/emotional problems, and autism spectrum disorder (ASD). This study evaluated the adaptive and behavioral developmental trajectories of children with TSC with and without a diagnosis of ASD at 36 months. METHODS: The Tuberous Sclerosis Complex Autism Center of Excellence Research Network study longitudinally assessed infants with TSC. Developmental (Mullen Scales of Early Learning), adaptive (Vineland Adaptive Behavior Scales, 2nd Edition, Survey Interview), and behavior/emotional (Child Behavior Checklist) functioning at 18, 24, and 36 months were examined in relationship to an ASD clinical diagnosis at 36 months. RESULTS: Deficits in all adaptive functioning domains were observed starting at age 18 months among those ultimately diagnosed with ASD but were largely explained after adjustment for developmental functioning except for lower social functioning at 36 months among individuals with ASD. Behavior/emotional problems did not consistently differ at 18 or 24 months, but nearly all emotional/behavioral problem domains were more severe in the children with ASD, relative to their peers without ASD at 36 months, even after adjusting for developmental functioning. These findings were not attributable to seizure burden. CONCLUSIONS: Although children with TSC and ASD did not differ in their adaptive functioning compared with children with TSC without ASD before 36 months, by 36 months, their social adjustment and emotional/behavioral functioning was significantly poorer than their peers without ASD, underscoring the importance of early detection of developmental concerns and targeted treatments.

Lien vers le texte intégral (Open Access ou abonnement)

13. Hwang DJ, Kim KR, Kim TK. Diminished Motivation for Voluntary Exercise and Metabolic Dysfunction in Psychiatric Disorders: A Behavioral Perspective on Autism Spectrum Disorder and Depression. Int Neurourol J. 2025; 29(Suppl 1): S3-s12.

PURPOSE: This study investigated spontaneous locomotor activity and metabolic phenotype in animal models of autism spectrum disorder (ASD) and major depressive disorder (MDD), with a focus on motivation to engage in voluntary exercise. METHODS: Spontaneous locomotion, voluntary wheel running, and metabolic phenotypes were assessed in Shank3B-knockout mice (ASD model) and stress-susceptible mice exposed to chronic restraint stress (CRSTSUS, MDD model) using indirect calorimetry and behavioral tests. RESULTS: Shank3B-knockout mice exhibited self-injurious repetitive behaviors resulting in skin lesions, while CRSTSUS mice showed behavioral despair indicative of stress vulnerability, along with a marked reduction in spontaneous locomotor activity and decreased motivation for voluntary exercise. Metabolic dysregulation was evident, including alterations in oxygen consumption, carbon dioxide production, respiratory exchange ratio, and energy expenditure. CONCLUSION: Behavioral and metabolic alterations in psychiatric disorders are closely linked, with reduced motivation for exercise emerging as a salient phenotypic signature. These findings highlight the need for targeted interventions that restore intrinsic motivation and energy balance. Future research should focus on elucidating the underlying mechanisms and developing therapies to enhance physical activity engagement in psychiatric conditions.

Lien vers le texte intégral (Open Access ou abonnement)

14. Issa F, Yerna X, Parpaite T, Jabbour C, Schakman O, Tajeddine N, Gualdani R, Gailly P. Conditional deletion of TRPC1 channel modulates synaptic plasticity, long term depression, and memory extinction in Fragile X syndrome mice. iScience. 2025; 28(8): 113085.

Group I metabotropic glutamate receptors (mGluRs), particularly mGluR5, regulate synaptic plasticity via long-term depression (mGluR-LTD), a process implicated in declarative memory. We previously identified TRPC1, a highly expressed hippocampal ion channel, as a key mGluR5 effector. Using a Cre-tamoxifen system, we acutely deleted Trpc1 in a Fragile X syndrome (FXS) mouse model, characterized by mGluR5 hyperactivity, enhanced mGluR-LTD, and social deficits. In FXS neurons, mGluR5-evoked currents were elevated and normalized by Trpc1 deletion. This deletion also improved social behavior and reduced anxiety. Notably, it abolished mGluR-LTD and normalized memory extinction, as shown in behavioral assays. Mechanistically, mGluR5 activation induced ARC protein expression via eEF2K- and ERK1/2-dependent pathways, modulating Arc translation and transcription. These findings highlight TRPC1 as a crucial mediator of pathological plasticity in FXS and a potential therapeutic target.

Lien vers le texte intégral (Open Access ou abonnement)

15. Javadfar Z, Soltani S, Khamoushi F, Sharifi M, Moradi S, Rezaeian S, Foroughi AA, Cheshmeh S, Taghaddosi M, Bahrehmand F. Effect of vitamin D supplementation on inflammatory status and behavioral symptoms in children with autism spectrum disorders: a double-blind randomized clinical trial. BMC Pediatr. 2025; 25(1): 615.

PURPOSE: Inflammation in early childhood has been proposed as a clinically recognized risk factor for developing autism spectrum disorder (ASD). Since vitamin D has an anti-inflammatory role, this trial was aimed to evaluate the effects of vitamin D supplementation on TNF-α and IL-37 status and behavioral problems in children with ASD. METHODS: This parallel double-blind clinical trial study was conducted on 43 ASD children who were randomly allocated into two studied groups the vitamin D drop group received 300 IU/kg daily (n = 22) and, the control group (n = 21) for 15 weeks. Serum levels of 25(OH) D (ng/ml), and inflammatory indices including tumor necrosis factor-alpha (TNF-α) (ng/ml), and interleukin 37 (IL-37) (ng/ml) were measured at the start and end of the study. Moreover, the Real-Life Rating Scale for Autism (RLRS) questionnaire assessed behavioral symptoms. RESULTS: Of the participants, 55.6% in the intervention group and 44.4% in the control group were boys (P = 0.24). After 15 weeks of vitamin D supplementation, serum 25(OH) D levels significantly increased (P = 0.001), while TNF-α (P < 0.001) and IL-37 (P = 0.004) levels significantly decreased. The total RLRS score in the intervention group significantly decreased (P = 0.005), but no significant changes were observed in its subcategories (e.g., Sensory Motor Behaviors, Social Relationship to People) due to small, non-significant improvements accumulating to affect the total score. Between-group comparisons for RLRS were non-significant (P = 0.165). CONCLUSION: The trial highlighted the possible anti-inflammatory role of vitamin D in children with ASD, as well as improving behavioral disorders. LEVEL OF EVIDENCE: Level I- randomized controlled trial. TRIAL REGISTRATION: IRCT20170827035936N3, https://irct.behdasht.gov.ir/trial/27012; registration date: 16/09/2023. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-025-05985-y.

Lien vers le texte intégral (Open Access ou abonnement)

16. Kacimi FE, Esselmani H, Ed-Day S, Nechchadi H, Merzouki M, Ramchoun M, Azzaoui FZ, Boulbaroud S. Vitamin A supplementation restores neuroanatomical integrity and behavior in a valproic acid-induced autism model. J Mol Histol. 2025; 56(4): 258.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviors, and cognitive impairments. Evidence suggests that Vitamin A deficiency (VAD) may exacerbate ASD-related abnormalities, while Vitamin A supplementation (VAS) may offer neuroprotection. This study investigates the effects of Vitamin A modulation on neuronal integrity, cognitive function, and social behavior in a valproic acid (VPA)-induced ASD rat model, focusing on histological changes, behavioral outcomes, and serum Vitamin A levels. Pregnant Wistar rats received VPA (500 mg/kg) on gestational day 12.5. Offspring were divided into Control, VPA, VAD, VPA + VAD, and VPA + VAS (2000 IU/kg diet) groups. Serum Vitamin A levels were quantified using spectrophotometry. Histopathological analysis of the hippocampus, cerebellum, and prefrontal cortex (PFC) assessed neuronal and glial cell densities. Behavioral tests included the Three-Chamber Social Interaction Test for sociability and the Novel Object Recognition Test for memory function. Serum analysis showed significantly lower Vitamin A levels in VAD and VPA + VAD groups, while VAS restored levels. Histological analysis revealed reduced neuronal density and increased glial activation in VPA, VAD, and VPA + VAD groups. The VPA + VAS group exhibited partial neuronal recovery. Behaviorally, VAS improved sociability and memory performance, correlating with neuronal preservation. These findings suggest that Vitamin A deficiency worsens ASD-related impairments, while supplementation restores neuronal integrity and cognitive function, highlighting its potential therapeutic role in ASD.

Lien vers le texte intégral (Open Access ou abonnement)

17. Kamp-Becker I, Poustka L. Media Consumption by Preschool Children: The Risk of Autism and Developmental Disorders. Dtsch Arztebl Int. 2025; (Forthcoming).

BACKGROUND: Autism spectrum disorder (ASD) is a persistent neurodevelopmental condition characterized by impaired social communication and the presence of restricted, repetitive patterns of behavior, typically manifesting in early childhood. The rising prevalence of ASD has been discussed in relation to increased media consumption. METHODS: A selective literature search was conducted in the Medline database on the topics of media consumption and mental disorders, particularly autism, in preschool children. Seven systematic reviews and meta-analyses and 36 original studies were included in the analysis. RESULTS: The findings across studies consistently demonstrated that media consumption in preschool children was associated with deficits in language and cognitive development (adjusted odds ratio [aOR] 1.67-2.28) and was a risk factor for the development of emotional, behavioral, and developmental disorders (aOR: 1.34-3.06). Symptoms consistent with ASD were also found to be associated with increased media consumption (OR 1.97, 95% confidence interval [1.30; 3.00]). However, these observed effects were consistently identified in the context of multiple other risk factors for mental health problems-such as low socioeconomic status, a family history of mental disorders, or parental stress-which mediated these effects, either directly or indirectly. Intervention studies showed that reducing media consumption, combined with an increase in constructive parent-child interactions, led to a reduction in symptom severity. CONCLUSION: In the context of additional risk factors, increased media consumption in young children is associated with atypical or delayed development. The extent of developmental disorders can be reduced through targeted support for parents. When risk factors are present, it is therefore essential to educate parents and implement preventive measures to promote the long-term healthy development of children.

Lien vers le texte intégral (Open Access ou abonnement)

18. Kang E, Rosen TE, Keifer CM, Gerber AH, Lerner MD. A single-blind active-control randomized controlled trial of group-based social competence intervention. Sci Rep. 2025; 15(1): 28872.

This study evaluated specific effects of a blinded randomized controlled trial of a group-based social skills intervention, Socio-Dramatic Affective-Relational Intervention (SDARI), against an active attention control (AC) intervention. Fifty-five autistic youth (M(age)=12.40; SD(age)=2.92; 73% boys) were randomly allocated to either the SDARI or the AC condition. Both interventions comprised 10 weekly sessions and were tightly matched for structure, participant age, IQ, and gender, such that the specific activities of SDARI were directly examined. Multimethod assessments at pre-, post-treatment, and 10-week follow-up included informant-reported social skills and autism-related behaviors, observer-rated spontaneous peer interaction, peer-rated friendships, and a metric of social information processing (the N170 event-related potential). Parent expectancy effect was also explored by examining perceived conditions by parents/caregivers, who were blinded to the condition assignment. Compared to the AC condition, the SDARI group evinced improvements in the N170 latency, rapid peer-liking, and reciprocal friendships at endpoint and follow-up. While the conditions did not differ on parent-reported social skills or autism-related behaviors, a parental expectancy effect was found where parent-rated social skills improvements were related to parents’ perceived conditions. These results provide support for the efficacy of the specific SDARI activities on several objective, reliable outcomes of social functioning in autistic youth.

Lien vers le texte intégral (Open Access ou abonnement)

19. Karaçam Doğan M, Fusar-Poli L, Arias-Magnasco A, Pries LK, Lin BD, Klingenberg B, Bortoletto R, Colizzi M, Menne-Lothmann C, Decoster J, van Winkel R, Collip D, Delespaul P, De Hert M, Derom C, Thiery E, Jacobs N, van Os J, Rutten B, Luykx J, Prachason T, Guloksuz S. Examining psychological protective mechanisms as moderators of the association between autistic traits and psychosis expression in a general population twin sample. Schizophr Res. 2025; 284: 133-40.

BACKGROUND: Psychological protective factors, such as coping styles, extraversion, and optimal parenting, may reduce the risk of psychosis. However, their role in moderating the association between autistic traits (ATs) and psychosis expression (PE) remains understudied. METHODS: This study analyzed the first-wave data from the TwinssCan Project (n = 792 twins and siblings, 60.2 % female, mean age = 17.4 ± 3.6). ATs and PE were assessed using the Autism-Spectrum Quotient and the Community Assessment of Psychic Experiences (CAPE), respectively. Multilevel linear regression models were used to evaluate the moderating effects of seven coping styles (active coping, avoidance, reassuring thoughts, expressing emotions, seeking social support, palliative-reacting, and passive-reacting coping), extraversion, and optimal parenting. RESULTS: Seeking social support (B[95 %CI]:-0.005[-0.009,-0.001]), reassuring thoughts (B[95 %CI]:-0.005[-0.009,-0.001]), extraversion (B[95 %CI]: -0.03[-0.04,-0.01]) and optimal parenting (B[95 %CI]: -0.02[-0.03,0]) weakened the associations between ATs and CAPE total frequency scores, suggestive of protective mechanisms, whereas passive-reacting coping (B[95 %CI]:0.007[0.004,0.010]) strengthened this, suggestive of a risk factor. Additionally, avoidance(B[95 %CI]:0.09[0.02,0.16]) emerged as a risk factor in confirmatory analyses by significantly interacting with ATs in predicting CAPE total severity scores. CONCLUSIONS: Engagement coping, extraversion, and optimal parenting may mitigate psychosis vulnerability in individuals with higher ATs, while passive-reactive coping and avoidance may heighten psychosis vulnerability. Although further research is needed, our findings provide a rationale for developing and testing targeted preventive strategies aimed at enhancing resilience in individuals with ATs.

Lien vers le texte intégral (Open Access ou abonnement)

20. Kranz D, Braverman Y, McCarthy M, Mackay C, Sabol K, Benke TA, Lieberman D, Marsh ED, Neul JL, Peck F, Percy AK, Saby J, Kopell N, Nelson CA, Levin AR, Fagiolini M. Altered oscillatory coupling reflects possible inhibitory interneuron dysfunction in Rett syndrome. medRxiv. 2025.

BACKGROUND: Rett syndrome is a rare neurodevelopmental disorder caused primarily by pathogenic variants in the MECP2 gene, leading to lifelong cognitive impairments. To understand the broad neural disruptions in Rett syndrome, it is essential to examine large-scale brain dynamics at the level of neural oscillations. Phase-amplitude coupling-a form of cross-frequency interaction that supports information integration across temporal and spatial scales-is a promising candidate measure for capturing such widespread neural dysfunction. Phase-amplitude coupling depends on the coordinated activity of specific neuronal subtypes, and while multiple subtypes are implicated in different aspects of the Rett syndrome phenotype, their role in shaping large-scale oscillatory dynamics in Rett syndrome is not well understood. To investigate this, we utilized a multi-level approach, combining EEG recordings with computational modeling to identify alterations in phase-amplitude coupling in Rett syndrome and probe their underlying cellular and circuit-level mechanisms. METHODS: We recorded resting-state EEG from 38 individuals with Rett syndrome and 30 age- and sex-matched typically developing individuals. Phase-amplitude coupling was quantified: modulation index was obtained to determine coupling strength, and phase bias was assessed to examine the preferred phase of coupling. We characterized phase-amplitude coupling across all low and high frequency combinations and electrodes, as well as within canonical theta-gamma and alpha-gamma frequency pairs across four predefined cortical regions. Finally, we modeled a biophysically-constrained Layer 4 cortical network to propose a possible mechanism underlying changes to oscillatory dynamics. RESULTS: We found significantly stronger phase-amplitude coupling in Rett syndrome across widespread cortical regions and frequency pairs, with a pronounced increase in theta-gamma and alpha-gamma coupling in anterior, posterior, and whole-brain regions (P < 0.05). Individuals with Rett syndrome also exhibited a more positive alpha-gamma phase bias in anterior and whole-brain regions (P < 0.05). Biophysically constrained modelling demonstrated that reduced VIP-expressing interneuron activity alone could recapitulate the pattern of increased theta-gamma and alpha-gamma phase-amplitude coupling observed in Rett syndrome (P < 0.001). CONCLUSIONS: These findings identify alterations in awake-state phase-amplitude coupling in Rett syndrome and propose a mechanistic link to VIP+ interneuron dysfunction. Elevated phase-amplitude coupling may serve as a promising biomarker of cortical dysfunction and a translational bridge from neural circuitry to clinically observable EEG signatures. By implicating VIP+ interneurons, our results open new avenues for testing interventions in preclinical models to identify potential novel therapeutic targets for individuals with Rett syndrome.

Lien vers le texte intégral (Open Access ou abonnement)

21. Le Pong J, Howe TH, Chen HL, Weng ZC, Wang TN. Enhancing Handwriting Performance in Autistic Children: A Randomized Crossover Study on the Effectiveness of a Spatial-Structured Handwriting Intervention Program. Autism Res. 2025.

Handwriting is an essential skill for school-aged children. Research indicates that autistic children often demonstrate poor handwriting fundamentals, which significantly affect their handwriting performance. These children also often exhibit weak central coherence (WCC), a cognitive visual processing characteristic that impairs their ability to integrate details into a cohesive whole in writing tasks. This challenge is particularly pronounced in logographic handwriting, where spatial relationships between radicals are essential for legibility, adding another layer of complexity. The modified geometric-based handwriting intervention program was designed to improve fundamental skills while addressing the spatial demands of logographic characters and the impact of WCC for autistic children. Twenty-two first- and second-grade autistic students were recruited and received a 12-h one-on-one handwriting intervention. Assessments of handwriting performance (legibility and speed), fundamental skills (visual perception, fine motor coordination, and visual-motor integration), and acceptability (motivation and satisfaction) were collected for data analysis. Results showed significant improvements in handwriting legibility, visual perception, and fine motor coordination, with high acceptance ratings from both participants and caregivers. This study provides evidence that the program effectively enhances handwriting legibility and foundational skills while maintaining high motivation levels in autistic children.

Lien vers le texte intégral (Open Access ou abonnement)

22. Li M, Qiao Z, Li J, Zhou H, Huang D, Cai Y, Li X, Zhang Z, Zhou J, Zhou J. Prenatal valproic acid on the basis of gestational diabetes also induces autistic behavior and disrupts myelination and oligodendroglial maturation slightly in offspring. Transl Psychiatry. 2025; 15(1): 271.

INTRODUCTION: Gestational diabetes mellitus (GDM) and prenatal exposure to valproic acid (VPA) are both constitute risk factors for autism in progeny. Notably, dysmyelination in the corpus callosum serves as a prominent element connecting GDM and autism in the white matter lesions. OBJECTIVE: The cumulative effects of GDM and prenatal VPA on both autistic behavior and dysmyelination in progeny have been investigated in this study. METHODS: In vivo, female mice exhibiting leptin receptor deficiencies and maintained on a high-fat diet were utilized to create GDM models, to which prenatal VPA was administered. In vitro, oligodendrocyte precursor cells (OPCs) were treated with VPA in the high-fat and high-glucose culture. RESULTS: The offspring subjected to both GDM and prenatal VPA demonstrated comparable declines in social interaction, myelination, and OPC maturation, akin to those exclusively exposed to VPA. Remarkably, the application of clemastine facilitated remyelination, ameliorated autistic behaviors, and promoted the progression of OPCs. Furthermore, the compromised myelination and OPC maturation instigated by the combination of GDM and prenatal VPA were found to be less severe compared to those precipitated by VPA alone. This differential impact can be attributed to the opposing influences of GDM and VPA on gamma-aminobutyric acid receptor activation in OPCs, extracellular regulated protein kinases (ERK) phosphorylation in OPCs, and the modulation of histone deacetylase 3 and dual specificity phosphatase 5 expression. CONCLUSIONS: we delineate the antagonistic effects of GDM and prenatal VPA on ERK phosphorylation in fetal OPCs, consequently altering their proliferation and differentiation, thereby culminating in milder dysmyelination and autistic behaviors.

Lien vers le texte intégral (Open Access ou abonnement)

23. Lopes LPN, Raimundo ACS, Itria A, Caetano R, Lopes LC. Recalculation of the budgetary impact of risperidone use for Autism Spectrum Disorder: a case study using measured demand data, Brazil, 2017-2019. Epidemiol Serv Saude. 2025; 34: e20240732.

OBJECTIVE: To analyze the budgetary impact of use of risperidone for autism spectrum disorder (ASD) in the Brazilian National Health System (SUS). METHODS: This is a case study with a document-based approach, which compared the estimates of the budgetary impact analyses presented in the recommendation reports of the National Commission for the Incorporation of Technologies (CONITEC) for the use of risperidone for ASD with amounts recalculated from measured demand data. The recalculation for children (0-17 years) and adults (≥18 years) was made using data from the Open Health Intelligence Room platform on the dispensing of risperidone in the SUS, considering a three-year time period (2017-2019). RESULTS: The total budgetary impact over three years of use of risperidone for ASD showed differences between measured demand (children: BRL 10,389,702.70; adults: BRL 15,075,767.80) and that estimated by CONITEC in its recommendation reports (children: R$ 6,579,809.00; adults: R$ 9,877,790.18). CONCLUSION: The budgetary impact of use of risperidone for ASD, based on measured demand, differed from the impact initially predicted in CONITEC’s recommendation reports.

Lien vers le texte intégral (Open Access ou abonnement)

24. Mavel S, Pellé L, Andres CR. Impact of maternal microbiota imbalance during pregnancy on fetal cerebral neurodevelopment: Is there a link to certain autistic disorders?. Brain Behav Immun Health. 2025; 48: 101074.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with a heterogeneous group of psychiatric disorders primarily characterized by impairments in communication and social interactions. ASD typically emerges around 18 months of age. While no single etiology has been identified, theories suggest a combination of genetic predisposition and environmental factors, such as exposure to toxics, viral infections, and neuroinflammatory processes. However, the mechanisms linking environmental risk factors to ASD remain poorly understood, particularly during the prenatal period. Among the various hypotheses, the gut microbiota has been proposed as a potential modulator of nervous system development and function. During pregnancy, the maternal microbiota could trigger gestational inflammatory responses, leading to maternal immune activation (MIA). These deleterious processes could play a causal role in the etiopathogenesis of neurodevelopmental disorders in offspring. The gut microbiota could be the missing link between genetic susceptibility and environmental exposures in certain forms of ASD. The gut microbiome induces the production of microbiota-derived signaling metabolites, immune mediators, gut hormones, and neural signaling via the spinal cord and vagus nerve. This review synthesizes the current knowledge from preclinical rodent models and human studies that investigate the impact of the maternal gut microbiota during pregnancy on ASD risk in offspring. Additionally, the potential roles of the maternal oral and vaginal microbiota are also discussed in the context of this maternal-offspring pairing. Finally, we examine how restoring maternal microbiome balance, through interventions such as pre/probiotics, may help reduce the perinatal risk of certain ASD by positively influencing prenatal environmental factors.

Lien vers le texte intégral (Open Access ou abonnement)

25. Milo Rasouly H, Krishna Murthy SB, Vena N, Povysil G, Beenken A, Verbitsky M, Shril S, Lekkerkerker I, Yang S, Khan A, Fasel D, Wongboonsin J, Martino J, Ke J, Elefant N, Tomar N, Harnof O, Kisselev S, Bheda S, Reytan-Miron S, Lim TY, Jamry-Dziurla A, Lugani F, Zhang JY, Marasa M, Kolupaeva V, Groopman EE, Jin G, Ghavami I, Stevens KO, Coughlin AC, Kil BH, Chatterjee D, Bradbury D, Zheng J, Mehl K, Morban M, Reingold R, Piva S, Mu X, Mittrori A, Szmigielska A, Gliwińska A, Ranghino A, Bomback AS, Badenski A, Latos-Bielenska A, Capone V, Materna-Kiryluk A, Amoroso A, Izzi C, La Scola C, Cohen DJ, Santoro D, Drozdz D, Fiaccadori E, Lin F, Scolari F, Tondolo F, La Manna G, Appel GB, Ghiggeri GM, Zaza G, Montini G, Masnata G, Krzemien G, Pisani I, Radhakrishnan J, Zachwieja K, Gesualdo L, Biancone L, Meneghesso D, Mizerska-Wasiak M, Tkaczyk M, Zaniew M, Borszewska-Kornacka MK, Szczepanska M, Saraga M, Rao MK, Bodria M, Miklaszewska M, Uy NS, Baraldi O, Bjanid O, Esposito P, Zamboli P, Marzuillo P, Canetta PA, Sikora P, Westland R, Crew RJ, Alam S, Guarino S, Negrisolo S, Hays T, Mane S, Grandinetti V, Tasic V, Lozanovski VJ, Caliskan Y, Goldstein D, Lifton RP, Ionita-Laza I, Kiryluk K, van Eerde AM, Hildebrandt F, Sanna-Cherchi S, Gharavi AG. Exome analysis links kidney malformations to developmental disorders and reveals causal genes. Nat Commun. 2025; 16(1): 7290.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are developmental disorders that commonly cause pediatric chronic kidney disease and mortality. We examine here rare coding variants in 248 CAKUT trios and 1742 singleton CAKUT cases and compare them to 22,258 controls. Diagnostic and candidate diagnostic variants are detected in 14.1% of cases. We find a significant enrichment of rare damaging variants in constrained genes expressed during kidney development and in genes associated with other developmental disorders, suggesting phenotype expansion. Consistent with these data, 18% of CAKUT patients with diagnostic variants have neurodevelopmental or cardiac phenotypes. We identify 40 candidate genes, including CELSR1, SSBP2, XPO1, NR6A1, and ARID3A. Two are confirmed as CAKUT genes: ARID3A and NR6A1. This study suggests that many yet-unidentified syndromes would be discoverable with larger cohorts and cross-phenotype analysis, leading to clarification of the genetic and phenotypic spectrum of developmental disorders.

Lien vers le texte intégral (Open Access ou abonnement)

26. Moon H, Sloofman L, Avila MN, Klei L, Devlin B, Buxbaum JD, Roeder K. A framework to infer de novo exonic variants when parental genotypes are missing enhances association studies of autism. bioRxiv. 2025.

MOTIVATION: Gene-damaging mutations are highly informative for studies seeking to discover genes underlying developmental disorders. Traditionally, these de novo variants are recognized by evaluating high-quality DNA sequence from affected offspring and parents. However, when parental sequence is unavailable, methods are required to infer de novo status and use this inference for association studies. RESULTS: We use data from autism spectrum disorder to illustrate and evaluate methods. Separating de novo from rare inherited variants is challenging because the latter are far more common. Using a classifier for unbalanced data and variants of known inheritance class, we build an inheritance model and then a de novo score for variants when parental data are missing. Next, we propose a new Random Draw (RD) model to use this score for gene discovery. Built into an existing inferential framework, RD produces a more powerful gene-based association test and controls the false discovery rate. AVAILABILITY AND IMPLEMENTATION: The implementation code and publicly available data are provided at: https://github.com/HaeunM/TADA-RD.

Lien vers le texte intégral (Open Access ou abonnement)

27. Morgan E, Punches B, Failla M. Self-Reported Diagnosis of Autism Is Associated With a Lower Likelihood of HIV Testing. J Acquir Immune Defic Syndr. 2024; 97(4): e6-e9.

Sexuality and sexual risk behaviors among autistic adults are often overlooked, resulting in inadequate sexual education courses and a reliance on peers or the internet as primary sources of information. Here, we plan to begin to fill this gap by assessing HIV and sexually transmitted infection (STI) outcomes among autistic adults. Data come from the 2007 NHIS data set, the only nationally representative and publicly available data set to host measures of HIV and autism alongside one another (and the only year of this survey to do so). Survey-weighted models were used to examine the association between self-reported measures of HIV/STIs and self-reported autism diagnosis. Compared with those who had not been told that they have autism, participants with an autism diagnosis had lower odds of ever having an HIV test in their lifetime (adjusted odds ratio [aOR] = 0.05; 95% confidence interval [CI]: 0.01 to 0.26). No association was observed between autism diagnosis and plans for an HIV test within the next year, nor did any autistic adults report testing positive for any STI within the past 5 years. These results suggest that further research is needed among the autism spectrum disorder community, particularly in terms of achieving the US goal of ending the HIV epidemic by 2030.

Lien vers le texte intégral (Open Access ou abonnement)

28. Mortazavi M, Guevara J, Diaz J, Tran S, Ziaei Jam H, Batalov S, Bainbridge M, Besterman AD, Gymrek M, Palmer AA, Sebat J. Long Read Genome Sequencing Elucidates Diverse Functional Consequences of Structural and Repeat Variation in Autism. medRxiv. 2025.

Long-read whole genome sequencing (LR-WGS) technologies enhance the discovery of structural variants (SVs) and tandem repeats (TRs). Application of LR-WGS has potential to identify novel risk factors that contribute to autism spectrum disorder (ASD). We performed LR-WGS on 243 individuals from 63 ASD families and generated an integrated call set combining long- and short-read data. LR-WGS increased detection of gene-disrupting SVs and TRs by 29% and 38%, respectively, and enabled identification of novel exonic de novo germline and somatic SVs that were not detected previously with short read WGS. We observed complex SV patterns, including a previously undescribed class of nested duplication-deletion (DUP-DEL) events. Joint analysis of phased TRs and methylation data revealed that hypermethylation of expanded FMR1 alleles (≥35 CGG repeats) in females occurs independently of X chromosome inactivation. Rare SVs, TRs, and damaging SNVs together accounted for 6.2% (95% CI: 1.7-15%) of the heritability of ASD in this sample. These findings demonstrate how LR-WGS can resolve complex genetic variation and its functional consequences and regulatory effects in a single assay.

Lien vers le texte intégral (Open Access ou abonnement)

29. Parish-Morris J. Viewing Early Diagnosis Through a Developmental Lens-« Autistic, Yet Still a Girl ». JAMA Netw Open. 2025; 8(8): e2525893.

Lien vers le texte intégral (Open Access ou abonnement)

30. Prahl A, Fraze K, Kannan A, Grauzer J, Sturdivant RX. Functional Reading Activities to Motivate and Empower for Young Adults With Intellectual or Developmental Disabilities: A Randomized Pilot Trial. Am J Speech Lang Pathol. 2025: 1-17.

PURPOSE: Reading proficiency is an important life skill that contributes to improved quality of life and becoming an active member in society. This pilot randomized clinical trial tested the effects of a functional literacy intervention in young adults with intellectual and/or developmental disabilities (IDDs). METHOD: Participants included 44 young adults with IDD between 18 and 26 years old. Participants were randomly assigned to the Functional Reading Activities to Motivate and Empower (FRAME) treatment group or a « business-as-usual » control group. Participants participated in 24 twice-weekly sessions in which they were taught reading comprehension strategies in the context of functional text stimuli or activities of daily living that require reading (e.g., text messages, e-mails). The primary outcome measure was the number of reading comprehension strategies used. Secondary outcomes included (a) multiple-choice comprehension questions, (b) text message response, (c) e-mail response, (d) summarization, and (e) verbal responses to functional text samples. RESULTS: Young adults with IDD in the treatment group made statistically significant gains in use of reading comprehension strategies (d = 1.09, p = .002) and multiple-choice comprehension questions (d = 0.79, p = .038) as compared with the control group. There were no statistically significant differences on the remaining outcome measures. CONCLUSIONS: This study provides preliminary support for the short-term effects of the FRAME intervention for young adults with IDD, with particular emphasis on explicit reading comprehension strategy instruction within a functional context. Therapeutic services typically end during the transition period for young adults with disabilities. However, it is essential that evidence-based literacy supports are available as this is a skill that continues to develop throughout the lifespan and has the potential to transform an individual’s transition to adulthood and independence. Future research should include a larger clinical trial and evaluate mediators of intervention effects.

Lien vers le texte intégral (Open Access ou abonnement)

31. Reaven J, Cosgrove KT, Losh A, Nickles S, Kerns CM, Pickard K, Blakeley-Smith A, Hayutin L, Meyer AT, Middleton C, Reyes NM, Boles RE. Facing your fears in schools: using the ADIS/ASA to characterize anxiety and intervention outcomes in students with autism or suspected autism. Front Psychiatry. 2025; 16: 1569435.

BACKGROUND: Autistic youth are at higher risk of developing anxiety compared to their peers, with as many as 40% experiencing clinical anxiety. Emerging research suggests that these rates are an underestimate as distinct presentations of anxiety (e.g., fear of change, idiosyncratic fears) are often not recognized. CBT is a well-established approach for managing anxiety in autistic youth, but many have difficulty accessing these interventions. School-based CBT programs, like Facing Your Fears in Schools (FYF-S), have shown effectiveness in reducing anxiety in autistic students and may increase access to care. The Anxiety and Related Disorders Interview Schedule for DSM-5 with Autism Spectrum Addendum is a semi-structured interview that captures both DSM-5 and distinct presentations of anxiety. This study aimed to: 1) characterize a subsample of students with autism or suspected autism and anxiety and 2) examine effectiveness of FYF-S using the ADIS/ASA. METHODS: This study utilized a subsample of students (N=37; ages 7-14) from a larger Type 1 hybrid-effectiveness trial who had either autism or suspected autism. Students were randomized to either FYF-S or Usual Care (UC). Caregivers completed the ADIS/ASA at baseline and post-intervention. The ADIS/ASA was administered by clinicians rigorously trained to reliability and masked to condition. RESULTS: Students had both DSM-5 and distinct anxiety diagnoses at Time 1. Further, students in FYF-S demonstrated significant reductions in anxiety compared to UC, as evidenced by fewer anxiety diagnoses overall and significant improvement in total anxiety. CONCLUSION: This is the first school-based study using the ADIS/ASA to characterize anxiety and measure outcomes in autistic students. Overall, results indicate that FYF-S may be a promising school-based intervention for autistic youth. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT03685474, identifier NCT03685474.

Lien vers le texte intégral (Open Access ou abonnement)

32. Siedler A, Zasępa E, Idczak-Paceś E, Saad D, Zębrowska I. Coping strategies as mediators of internalizing symptoms on quality of life in school-aged children with autism spectrum disorder and typical development. Res Dev Disabil. 2025; 164: 105083.

BACKGROUND: Children with autism spectrum disorder (ASD) often report lower quality of life (QoL) than their typically developing peers, yet the coping processes that underlie these differences remain unclear. AIMS: This study investigated which coping styles mediate the impact of internalizing symptoms (depression, anxiety, anger control difficulties) on children’s self-reported QoL and whether these pathways differ between ASD and typically developing groups. METHODS: A total of 172 school-aged children (80 ASD and 92 typically developing) completed standardized measures of QoL, internalizing symptoms, and four coping styles. Moderated mediation analyses tested coping as parallel mediators and diagnostic group as a moderator. RESULTS: Across both groups, higher internalizing symptoms were linked to poorer QoL. Problem-solving coping emerged as a protective mediator in typically developing children only, while other coping styles did not mediate symptom-QoL links in either group. CONCLUSIONS: Problem-focused coping supports QoL in typically developing youth but appears less effective in ASD. Children with ASD derived immediate relief from palliative strategies (e.g., structured calming techniques), yet these strategies did not attenuate the negative impact of internal distress on their broader day-to-day well-being. Interventions that adapt problem-solving strategies to the needs of children with ASD may enhance their well-being.

Lien vers le texte intégral (Open Access ou abonnement)

33. Sui Y, Lin J, Noyes MD, Kwon Y, Wong I, Koundinya N, Harvey WT, Wu M, Hoekzema K, Munson KM, Garcia GH, Knuth J, Wertz J, Wang T, Hennick K, Karunakaran D, Polo Prieto RA, Meyer-Schuman R, Cherry F, Pehlivan D, Suter B, Gustafson JA, Miller DE, Berk-Rauch H, Nowakowski TJ, Chakravarti A, Zoghbi HY, Eichler EE. Pangenome discovery of missing autism variants. medRxiv. 2025.

Autism spectrum disorders (ASDs) are genetically and phenotypically heterogeneous and the majority of cases still remain genetically unresolved. To better understand large-effect pathogenic variation, we generated long-read sequencing data to construct phased and near-complete genome assemblies (average contig N50=43 Mbp, QV=56) for 189 individuals from 51 families with unsolved cases of autism. We applied read- and assembly-based strategies to facilitate comprehensive characterization of de novo mutations (DNMs), structural variants (SVs), and DNA methylation profiles. Merging common SVs obtained from long-read pangenome controls, we efficiently filtered >97% of common SVs exclusive to 87 offspring. We find no evidence of increased autosomal SV burden for probands when compared to unaffected siblings yet note a trend for an increase of SV burden on the X chromosome among affected females. We establish a workflow to prioritize potential pathogenic variants by integrating autism risk genes and putative noncoding regulatory elements defined from ATAC-seq and CUT&Tag data from the developing cortex. In total, we identified three pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, as well as nine candidate de novo and biparental homozygous SVs, most of which were missed by short-read sequencing. Our work highlights the potential of phased genomes to discover complex more pathogenic mutations and the power of the pangenome to restrict the focus on an increasingly smaller number of SVs for clinical evaluation.

Lien vers le texte intégral (Open Access ou abonnement)

34. Yamada S, Kumoi H, Sasaki H, Nakagawa Y. Leap motion-based bimanual coordination analysis in schizophrenia and autism spectrum disorder. J Psychiatr Res. 2025; 190: 248-54.

Impairments in bimanual coordination have been reported in schizophrenia and autism spectrum disorder (ASD), yet their characteristics and specificity remain unclear. This study employed a Leap Motion Controller (LMC) to assess fine motor coordination in 24 patients with schizophrenia, 19 individuals with ASD, and 20 healthy controls (HCs) using a bimanual peg pinch task. Coordination was quantified through spatial symmetry and temporal phase locking (PLV) of index and thumb movements. Individuals with schizophrenia showed significant impairments in both spatial and temporal coordination compared to HCs, consistent with prior literature and supporting the notion that such motor deficits may reflect neurodevelopmental anomalies. In contrast, no significant group-level differences were found between the ASD and HC groups, although the ASD group exhibited reduced variability in spatial metrics (e.g., box length), suggesting subtle but consistent coordination irregularities. These findings may be attributable to the characteristics of the ASD sample-relatively high-functioning adults diagnosed in adolescence or adulthood-whose motor profiles and developmental experiences may differ from those diagnosed in early childhood. Importantly, the study implies that PLV may not sufficiently capture spatial asymmetries observed in ASD, while spatial metrics such as size asymmetry may offer better sensitivity. Future research should employ spatially sensitive tools and stratified sampling to better characterize motor profiles in ASD and in psychiatric conditions involving neurodevelopmental disruption, such as schizophrenia. Combined with advanced analytic methods, LMC-based assessment may contribute to noninvasive early detection and differential diagnosis across such conditions.

Lien vers le texte intégral (Open Access ou abonnement)

35. Yusuf M, Genovese AC. Letter: Evolving Clinical Evidence: Electroencephalography Abnormalities in Autism Spectrum Disorder and the Emerging Role of Neuroelectric Biomarkers in Psychiatry. J Child Adolesc Psychopharmacol. 2025.

Lien vers le texte intégral (Open Access ou abonnement)