1. Boström AED, Andersson P, Wachtel LE, Jarbin H, Jokinen J, Lundberg J. Association between autism diagnosis rates and adolescent depression: A population-based study in Sweden. Psychiatry Res;2024 (Dec 25);344:116341.

INTRODUCTION: The association between increasing diagnosis rates of autism-related disorders (ASD-R) in Swedish regions and diagnosis rates of major depressive disorders (MDD) in adolescents remains unexplored. METHODS: Following STROBE guidelines, this pre-registered (https://osf.io/duvq7) observational study, utilizing registry data from 2008 to 2022 across the 21 Swedish regions, employed a generalized linear mixed model (GLMM) to analyze the association between ASD-R (ICD-10: F84) and MDD diagnosis rates (ICD-10: F32) in 15-19 year olds, with registered primary diagnoses considered. The GLMM included psychiatric care affiliation rates (PCAR) as fixed effects and variations across years and regions as random intercepts. The model incorporated bipolar disorder (BD) rates and the male-to-female ratio of ASD-R diagnoses when justified. Separate models were created for combined sexes, males, and females. RESULTS: A significant inverse relationship was observed between ASD-R and MDD diagnosis rates across all sex groups. In the combined-sex model, the mean ratio was 0.40 (P = 0.003), while the sex-specific models showed ratios of 0.28 for males (P < 0.001) and 0.37 for females (P = 0.017). All ratios were significantly below 1, indicating a negative association between ASD-R and MDD diagnosis rates. CONCLUSIONS: The study's observational nature limits causal inferences, but findings reveal that higher primary diagnosis rates of ASD-R correlate with lower primary diagnosis rates of MDD in adolescents of both sexes, although more pronounced in males. These results highlight the importance of further research on the relationship between ASD-R and MDD diagnosis rates, emphasizing the need for prospective, longitudinal, and individualized register data that include both primary and co-diagnoses.

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2. Bottema-Beutel K, Guo R, Braun C, Dunham-Carr K, Markfeld JE, Pulliam G, Clark SM, Keçeli-Kaysılı B, Feldman JI, Woynaroski T. Considerations for Measuring Caregiver Talk in Interactions With Infants at Elevated and Population-Level Likelihood for Autism: Deriving Stable Estimates. J Speech Lang Hear Res;2025 (Jan 2);68(1):234-247.

PURPOSE: This study aims to help researchers design observational measurement systems that yield sufficiently stable scores for estimating caregiver talk among caregivers of infant siblings of autistic and non-autistic children. Stable estimates minimize error introduced by facets of the measurement system, such as variability between coders or measurement sessions. METHOD: Analyses of variance were used to partition error variance between coder and session and to derive g coefficients. Decision studies determined the number of sessions and coders over which scores must be averaged to achieve sufficiently stable g coefficients (0.80). Twelve infants at elevated likelihood of an autism diagnosis and 12 infants with population-level likelihood of autism diagnosis participated in two semistructured observation sessions when the children were 12-18 months of age and again 9 months later. Caregiver follow-in talk was coded from these sessions. RESULTS: Two sessions and one coder were needed to achieve sufficient stability for follow-in talk and follow-in comments for both groups of infants at both time points. However, follow-in directives did not reach sufficient stability for any combination of sessions or coders for the population-level likelihood group at either time point, or for the elevated likelihood group at Time 2. CONCLUSION: Researchers should plan to collect at least two sessions to derive sufficiently stable estimates of caregiver talk in infants at elevated and general population-level likelihood for autism. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27996875.

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3. Ford ALB, Elmquist M, Johnson LD, Tapp J. Preliminary Examination of the Stability of Sequential Associations Between the Talk of Educators and Autistic Preschoolers Using Generalizability Theory. J Speech Lang Hear Res;2025 (Jan 2);68(1):248-258.

PURPOSE: Estimating the sequential associations between educators’ and children’s talk during language learning interactions requires careful consideration of factors that may impact measurement stability and resultant inferences. This research note will describe a preliminary study that used generalizability theory to understand the contribution of two measurement conditions-occasions and raters-on estimates of sequential associations between educator talk and autistic preschooler talk in inclusive preschool classrooms. METHOD: We used an existing data set of four 15-min video-recorded occasions of educator-child interactions for 11 autistic preschoolers during free-play in their inclusive classroom. Two trained raters coded all videos for preschooler talk and type of educator talk (i.e., opportunities for expressive language [OELs], other talk). We conducted two generalizability studies on sequential association estimates for two interaction directions (i.e., preschooler talk following educator OEL and educator talk following preschooler talk). We conducted a series of decision studies to explore configurations of measurement conditions to optimize future investigations. RESULTS: We had unstable estimates for both interaction directions in our current methodological approach, with raters accounting for minimal error and occasions accounting for considerable error. Future investigations would require at least six observation occasions for stable estimates of the sequential association between autistic preschooler talk following educator OEL that was stable after six occasions. More than 15 occasions were required for stable estimates of the association between educator talk following autistic preschooler talk. CONCLUSION: We will share recommendations and implications for future investigations to estimate educator and child talk sequential associations within preschool language interactions.

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4. Gonzalez D, Jonak CR, Bernabucci M, Molinaro G, Collins K, Assad SA, Gibson JR, Binder DK, Huber KM. Enhanced CB1 receptor function in GABAergic neurons mediates hyperexcitability and impaired sensory-driven synchrony of cortical circuits in Fragile X Syndrome model mice. bioRxiv;2025 (Jan 2)

Electroencephalographic (EEG) recordings in individuals with Fragile X Syndrome (FXS) and the mouse model of FXS ( Fmr1 KO) display cortical hyperexcitability at rest, as well as deficits in sensory-driven cortical network synchrony. A form of circuit hyperexcitability is observed in ex vivo cortical slices of Fmr1 KO mice as prolonged persistent activity, or Up, states. It is unknown if the circuit mechanisms that cause prolonged Up states contribute to FXS-relevant EEG phenotypes. Here we examined the role of endocannabinoids (eCB) in prolonged Up states in slices and resting and sensory-driven EEG phenotypes in awake Fmr1 KO mice. Bidirectional changes in eCB function are reported in the Fmr1 KO that depend on synapse type (excitatory or inhibitory). We demonstrate that pharmacological or genetic reduction of Cannabinoid Receptor 1 (CB1R) in GABAergic neurons rescues prolonged cortical Up states and deficits in sensory-driven cortical synchrony in Fmr1 KO mice. In support of these findings, recordings from Fmr1 KO cortical Layer (L) 2/3 pyramidal neurons revealed enhanced CB1R-mediated suppression of inhibitory synaptic currents. In contrast, genetic reduction of Cnr1 in glutamatergic neurons did not affect Up state duration, but deletion of Fmr1 in the same neurons was sufficient to cause long Up states. These findings support a model where loss of Fmr1 in glutamatergic neurons leads to enhanced CB1R-mediated suppression of GABAergic synaptic transmission, prolonged cortical circuit activation and reduced sensory-driven circuit synchronization. Results suggest that antagonism of CB1Rs as a therapeutic strategy to correct sensory processing deficits in FXS.

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5. Lesire S, Lata R, Hoogvliets Y, Herrebosch K, Van De Velde P, Speleers A, Christ F, Van Belle S, Debyser Z. LEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates. Structure;2025 (Jan 2);33(1):78-90.e76.

Methyl-CpG-binding protein 2 (MeCP2) is a ubiquitously expressed nuclear protein involved in transcriptional regulation and chromatin remodeling. MeCP2 exists in two isoforms, MeCP2 E1 and E2, which share the same functional domains. Loss-of-function mutations in the MeCP2 gene are the main cause of Rett syndrome (RTT). Previous studies identified a complex formation between MeCP2 and lens epithelium derived growth factor (LEDGF), a transcriptional regulator that exists in two isoforms, LEDGF/p75 and LEDGF/p52. Here, we characterized the molecular and functional interaction between MeCP2 and LEDGF. The NCoR interaction domain (NID) domain in MeCP2 is essential for the direct binding to the PWWP-CR1 region of LEDGF. Introduction of R306C, an RTT mutation in the NID of MeCP2, reduced the interaction with LEDGF. Our data reveal mutual inhibition of MeCP2 and LEDGF multimerization due to overlapping binding sites. Aligning with this observation, LEDGF depletion resulted in larger MeCP2 and DNA foci in NIH3T3 cells, suggesting a role for the MeCP2-LEDGF complex in chromatin organization.

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6. Linert J, Finestack LH, Abbeduto L. Syntactic Growth of Adolescent Boys With Fragile X Syndrome or Down Syndrome: A Longitudinal Study. J Speech Lang Hear Res;2025 (Jan 2);68(1):193-215.

PURPOSE: The current study addresses a gap in the literature regarding syntactic development of adolescent boys with fragile X syndrome (FXS) and Down syndrome (DS). Specifically, we ask whether syntactic skills plateau or continue to change during adolescence for these groups and whether the profile of syntactic change differs between boys with FXS and those with DS. METHOD: Participants were 38 boys with FXS (with and without autism) and 20 boys with DS between the ages of 10 and 16 years, as well as 33 boys who were neurotypical between the ages of 3 and 8 years at study entry. Trained examiners evaluated the participants annually for four consecutive years. The evaluation included standardized language assessments and a conversational language sample, which was analyzed using mean length of utterance-morphemes and the Index of Productive Syntax. For each measure, we fit a series of candidate models, including the intercept-only model and models with nonverbal cognition and maternal IQ as moderators. We then used Akaike’s information criteria-corrected to determine which model in a candidate set had the most empirical evidence. RESULTS: Our between-groups results indicated that FXS and DS have distinct syntactic profiles. However, our growth analyses and moderator analyses yielded mixed results. For most measures, the most likely models suggest that there is no plateau in the growth of syntactic skills for boys with FXS or DS and that nonverbal cognition is associated with the rate of change. CONCLUSIONS: These results suggest that syntactic change continues to occur throughout adolescence for boys with FXS or DS. The results also indicate that the growth profiles are distinct between the two groups. Future research with more participants from more diverse backgrounds would add more clarity to these findings. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27984548.

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7. Manzo J, Hernández-Aguilar ME, Toledo-Cárdenas MR, Herrera-Covarrubias D, Coria-Avila GA. Dysregulation of neural tube vascular development as an aetiological factor in autism spectrum disorder: Insights from valproic acid exposure. J Physiol;2025 (Jan 2)

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition affecting a substantial number of children globally, characterized by diverse aetiologies, including genetic and environmental factors. Emerging research suggests that neurovascular dysregulation during development could significantly contribute to autism. This review synthesizes the potential role of vascular abnormalities in the pathogenesis of ASD and explores insights from studies on valproic acid (VPA) exposure during neural tube development. VPA, a widely used antiepileptic drug and mood stabilizer, crosses the placental barrier and impacts the developing fetal brain. Studies indicate that VPA disrupts normal angiogenesis by reducing the expression levels of vascular endothelial growth factor A (VEGFA) and its receptors, and purinergic signalling, which are crucial for both vascular and neural development. Such disruptions may lead to abnormalities in neuronal migration and pathfinding, potentially contributing to the neural and behavioural manifestations of ASD. Thus despite the relatively limited findings, improper vascularization of the neural tube appears to be a contributing factor in the pathogenesis of ASD, as also suggested by VPA studies. Integrating these insights, it is hypothesized that vascular factors should be considered in the aetiological analysis of idiopathic autism.

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8. Marcassa G, Dascenco D, Lorente-Echeverría B, Daaboul D, Vandensteen J, Leysen E, Baltussen L, Howden AJM, de Wit J. Synaptic signatures and disease vulnerabilities of layer 5 pyramidal neurons. Nat Commun;2025 (Jan 2);16(1):228.

Cortical layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons are embedded in distinct information processing pathways. Their morphology, connectivity, electrophysiological properties, and role in behavior have been extensively analyzed. However, the molecular composition of their synapses remains largely uncharacterized. Here, we dissect the protein composition of the excitatory postsynaptic compartment of mouse L5 neurons in intact somatosensory circuits, using an optimized proximity biotinylation workflow with high spatial accuracy. We find distinct synaptic signatures of L5 IT and PT neurons that are defined by proteins regulating synaptic organization and transmission, including cell-surface proteins (CSPs), neurotransmitter receptors and ion channels. In addition, we find a differential vulnerability to disease, with a marked enrichment of autism risk genes in the synaptic signature of L5 IT neurons compared to PT neurons. These results align with human studies and suggest that the excitatory postsynaptic compartment of L5 IT neurons is susceptible in autism. Our approach is versatile and can be broadly applied to other neuron types to create a protein-based, synaptic atlas of cortical circuits.

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9. Markfeld JE, Kiemel Z, Santapuram P, Bordman SL, Pulliam G, Clark SM, Hampton LH, Keçeli-Kaysili B, Feldman JI, Woynaroski TG. Links Between Early Prelinguistic Communication and Later Expressive Language in Toddlers With Autistic and Non-Autistic Siblings. J Speech Lang Hear Res;2025 (Jan 2);68(1):178-192.

PURPOSE: The present study explored the extent to which early prelinguistic communication skills predict expressive language in toddlers with autistic siblings (Sibs-autism), who are known to be at high likelihood for autism and language disorder, and a comparison group of toddlers with non-autistic older siblings (Sibs-NA). METHOD: Participants were 51 toddlers (29 Sibs-autism, 22 Sibs-NA) aged 12-18 months at the first time point in the study (Time 1). Toddlers were seen again 9 months later (Time 2). Three prelinguistic communication skills (i.e., intentional communication, vocalization complexity, and responding to joint attention) were measured at Time 1 via the Communication and Symbolic Behavior Scales Developmental Profile-Behavior Sample. An expressive language aggregate was calculated for each participant at Time 2. A series of correlation and multiple regression models was run to evaluate associations of interest between prelinguistic communication skills as measured at Time 1 and expressive language as measured at Time 2. RESULTS: Vocalization complexity and intentional communication displayed significant zero-order correlations with expressive language across sibling groups. Vocal complexity and responding to joint attention did not have significant added value in predicting later expressive language, after covarying for intentional communication across groups. However, sibling group moderated the association between vocalization complexity and later expressive language, such that vocal complexity displayed incremental validity for predicting later expressive language, covarying for intentional communication, only within Sibs-NA. CONCLUSIONS: Results indicate that prelinguistic communication skills, in particular intentional communication, show promise for predicting later expressive language in siblings of autistic children. These findings provide additional empirical support for the notion that early preemptive interventions targeting prelinguistic communication skills, especially intentional communication, may have the potential to scaffold language acquisition and support more optimal language outcomes in this population at high likelihood for a future diagnosis of both autism and language disorder. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27745437.

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10. McMahon M, Cooney-Miner D, Bourne M, Brown H. Pilot educational intervention for the care of adolescents with autism spectrum disorder during puberty. J Am Assoc Nurse Pract;2025 (Jan 1);37(1):36-43.

Puberty is a particularly vulnerable time for individuals with autism spectrum disorder (ASD) during which baseline challenges are exacerbated, functioning often deteriorates, and additional barriers emerge. Specific concerns include increased vulnerability, decreased safety, and increased mood and behavioral disturbances. Youth with ASD need guidance and explicit instruction/skill development on topics such as hygiene/self-care, appropriate sexual activity, and menstruation management. Lack of provider preparation, knowledge, and confidence, along with stigma about the needs and capabilities of individuals with ASD, are major barriers to care. Initiatives to expand the preparation of health care personnel, including nurse practitioners, to provide quality care to individuals with ASD are essential. This article describes the results of a pilot project using a brief, self-guided educational intervention for developing and practicing family nurse practitioners. Before and after viewing the educational module, participants completed author-created surveys assessing their self-perceived knowledge, attitudes, and intent to change practice. Expert analysis of survey items provided face validity. Comparison of mean presurvey and postsurvey responses showed significant increases in self-perceived knowledge, attitudes, and intent to implement practice changes. Lack of confidence was endorsed as the most common remaining barrier to change. Findings indicate that the brief module improved participants’ self-reported knowledge, attitudes, and intent to implement practice recommendations. Such interventions can be easily incorporated into nursing education and professional development and are appropriate for dissemination to nurse practitioners working within and outside primary care settings, as well as to related service providers.

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11. Mendes M, Chen DZ, Engchuan W, Leal TP, Thiruvahindrapuram B, Trost B, Howe JL, Pellecchia G, Nalpathamkalam T, Alexandrova R, Salazar NB, McKee EA, Rivera-Alfaro N, Lai MC, Bandres-Ciga S, Roshandel D, Bradley CA, Anagnostou E, Sun L, Scherer SW. Chromosome X-wide common variant association study in autism spectrum disorder. Am J Hum Genet;2025 (Jan 2);112(1):135-153.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD. The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest symptoms similar to those in males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leaves them underrepresented in genome-wide studies. Here, we conducted an X-chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Collection (SSC), and Simons Powering Autism Research (SPARK), alongside 8,981 population controls (43% males). We analyzed 418,652 X chromosome variants, identifying 59 associated with ASD (p values 7.9 × 10(-6) to 1.51 × 10(-5)), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on Xp22.2 (lead SNP rs12687599, p = 3.57 × 10(-7)) harboring ASB9/ASB11 and another encompassing DDX53 and the PTCHD1-AS long non-coding RNA (lead SNP rs5926125, p = 9.47 × 10(-6)). When mapping genes within 10 kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD (GRPR, AP1S2, DDX53, HDAC8, PCDH19, PTCHD1, PCDH11X, PTCHD1-AS, DMD, SYAP1, CNKSR2, GLRA2, OFD1, CDKL5, GPRASP2, NXF5, and SH3KBP1). FGF13 emerged as an X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation.

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12. Mokhtar Tawfeek ES, Aly Abou Elez Gawish S, Hamed WS, Asker SA. Construction of an animal model of autism based on interaction between cerebellar histological, immunohistochemical, and biochemical changes in adult male albino rat. Ultrastruct Pathol;2025 (Jan 2);49(1):39-57.

METHODS: Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining. RESULTS: The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group. CONCLUSION: The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.

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13. Naguy A, Alayadhi N, Pridmore S, Alamiri B. Early Positive Report of Viloxazine for a Child with Hyperkinetic Autism. Psychopharmacol Bull;2025 (Jan 1);55(1):89-92.

Herein, authors report on an ASD child with comorbid ADHD, ID, metabolic syndrome and nocturnal enuresis that failed multiple trials of psychotropic agents for behavioural dyscontrol. Viloxazine adjuventia brought about remarkable improvement spanning different domains. Purported pharmacodynamic mechanisms are briefly discussed. This case represents one of the earliest reports of viloxazine use in ASD.

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14. Nakamura D, Hanawa Y, Seki S, Yamauchi M, Iwami Y, Nagatsuka Y, Suzuki H, Aoyagi K, Hayashi W, Otowa T, Iwanami A. Predictive model using autism diagnostic observation schedule, second edition for differential diagnosis between schizophrenia and autism spectrum disorder. Front Psychiatry;2024;15:1493158.

BACKGROUND: Although schizophrenia and autism spectrum disorder (ASD) are currently conceptualized as distinct disorders, the similarity in their symptoms often makes differential diagnosis difficult. This study aimed to identify similarities and differences in the symptoms of schizophrenia and ASD to establish a more useful and objective differential diagnostic method and to identify ASD traits in participants with schizophrenia. METHODS: A total of 40 participants with schizophrenia (13 females, mean age: 34 ± 11 years) and 50 participants with ASD (15 females, mean age: 34 ± 8 years) were evaluated using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and other clinical measures. RESULTS: ADOS-2 Module 4 original and revised algorithms did not significantly discriminate schizophrenia and ASD, whereas the « Predictive Model » combining the A7, A10, B1, B6, B8, and B9 showed superior accuracy in differentiating both disorders. Both algorithms in the ADOS-2 had high schizophrenia false-positive rates, and significant positive correlations were observed between all domains and the total scores of both algorithms in the ADOS-2 and Positive and Negative Syndrome Scale (PANSS) negative scale scores in the schizophrenia group. The PANSS negative-scale scores were significantly higher in patients positive for autism spectrum cut-offs (CutOff-POS) than in patients negative for autism spectrum cut-offs (CutOff-NEG) for both algorithms in the ADOS-2. Logistic regression analysis revealed that the positivity for both algorithm scales in the ADOS-2 was predicted using only the PANSS negative scale scores. CONCLUSIONS: This study showed that a combination of several items in the ADOS-2 is useful for discriminating between ASD and schizophrenia. The study’s findings could help develop strategies benefiting ASD and schizophrenia treatments.

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15. Ni LS, Wai Tong C, Kam Ki Stanley L. Effects of an acceptance and commitment-based parenting program for parents of children with autism spectrum disorder on parenting stress and other parent and children health outcomes: A pilot randomized controlled trial. Autism;2025 (Jan 2):13623613241311323.

This study aimed to examine whether an acceptance and commitment therapy (ACT)-based parenting program, incorporating topics of emotional and stress management, parenting skills training, autism-related education, and self-care learning, could be successfully implemented, well-received, and beneficial for parents of children with autism. We randomly assigned 40 parents to either participate in the eight-session ACT-based parenting program or receive usual care only. The program was found to be feasible, with many parents willing to participate and complete the sessions. The parents also reported high satisfaction with the program and found it beneficial, according to satisfaction surveys and interviews. The results showed that parents who participated in the ACT-based parenting program had significant improvements in several outcomes compared to parents in usual-care-only group, including reduced parenting stress, decreased depressive and anxiety symptoms, and increased confident in their parenting abilities. Their autistic children showed fewer emotional and behavioral problems after the intervention. Based on these findings, we conclude that the ACT-based parenting program is feasible and acceptable and has promising effects for parents of autistic children. In the future, larger studies should be conducted to further explore its effectiveness for different groups of parents caring for children with autism or other neurodevelopmental conditions.

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16. Nicholls T. Shrinking the autism employment gap: Finding out what really works. Autism;2025 (Jan 1):13623613241310926.

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17. Rad AB, Villavicencio T, Kiarashi Y, Anderson C, Foster J, Kwon H, Hamlin T, Lantz J, Clifford GD. From motion to emotion: exploring challenging behaviors in autism spectrum disorder through analysis of wearable physiology and movement. Physiol Meas;2025 (Jan 2)

OBJECTIVE: This study aims to evaluate the efficacy of wearable physiology and movement sensors in identifying a spectrum of challenging behaviors, including self-injurious behavior (SIB), in children and teenagers with autism spectrum disorder (ASD) in real-world settings. APPROACH: We utilized a long-short-term memory (LSTM) network with features derived using the wavelet scatter transform to analyze physiological biosignals, including electrodermal activity and skin temperature, alongside three-dimensional movement data captured via accelerometers. The study was conducted in naturalistic environments, focusing on participants’ daily activities. MAIN RESULTS: Our findings indicate that the best performance in detecting challenging behaviors was achieved using movement data. The results showed a sensitivity of 0.62, specificity of 0.71, F1-score of 0.36, and an area under the ROC curve of 0.71. These results are particularly significant given the study’s focus on real-world scenarios and the limited existing research in this area. SIGNIFICANCE: This study demonstrates that using wearable technology to record physiological and movement signals can detect challenging behaviors in children with ASD in real-world settings. This methodology has the potential to greatly improve the management of these behaviors, thereby enhancing the quality of life for children with ASD and their caregivers. This approach marks a significant step forward in applying the outcome of ASD research in practical, everyday environments.

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18. Sabeh P, Dumas SA, Maios C, Daghar H, Korzeniowski M, Rousseau J, Lines M, Guerin A, Millichap JJ, Landsverk M, Grebe T, Lindstrom K, Strober J, Ait Mouhoub T, Zweier C, Steinraths M, Hebebrand M, Callewaert B, Abou Jamra R, Kautza-Lucht M, Wegler M, Kruszka P, Kumps C, Banne E, Waberski MB, Dieux A, Raible S, Krantz I, Medne L, Pechter K, Villard L, Guerrini R, Bianchini C, Barba C, Mei D, Blanc X, Kallay C, Ranza E, Yang XR, O’Heir E, Donald KA, Murugasen S, Bruwer Z, Calikoglu M, Mathews JM, Lesieur-Sebellin M, Baujat G, Derive N, Pierson TM, Murrell JR, Shillington A, Ormieres C, Rondeau S, Reis A, Fernandez-Jaen A, Au PYB, Sweetser DA, Briere LC, Couque N, Perrin L, Schymick J, Gueguen P, Lefebvre M, Van Andel M, Juusola J, Antonarakis SE, Parker JA, Burnett BG, Campeau PM. Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability. Am J Hum Genet;2025 (Jan 2);112(1):75-86.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder. E3 ubiquitin ligases are responsible for transferring ubiquitin to substrate proteins to regulate a variety of cellular functions, including protein degradation, protein-protein interactions, and protein localization. Knocking out ubr-5 in C. elegans resulted in a lower movement score compared to the wild type, supporting a role for UBR5 in neurodevelopment. Using an in vitro autoubiquitination assay and confocal microscopy for the human protein, we found decreased ubiquitination activity and altered cellular localization in several variants found in our cohort compared to the wild type. In conclusion, we found that variants in UBR5 cause a neurodevelopmental syndrome that can be associated with a movement disorder, reinforcing the role of the UBR protein family in a neurodevelopmental disease that differs from previously described ubiquitin-ligase-related syndromes. We also provide evidence for the pathogenic potential loss of UBR5 function with functional experiments in C. elegans and in vitro ubiquitination assays.

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19. Scala M, Bradley CA, Howe JL, Trost B, Salazar NB, Shum C, Mendes M, Reuter MS, Anagnostou E, MacDonald JR, Ko SY, Frankland PW, Charlebois J, Elsabbagh M, Granger L, Anadiotis G, Pullano V, Brusco A, Keller R, Parisotto S, Pedro HF, Lusk L, McDonnell PP, Helbig I, Mullegama SV, Douine ED, Corona RI, Russell BE, Nelson SF, Graziano C, Schwab M, Simone L, Zara F, Scherer SW. Genetic variants in DDX53 contribute to autism spectrum disorder associated with the Xp22.11 locus. Am J Hum Genet;2025 (Jan 2);112(1):154-167.

Autism spectrum disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exon PTCHD1, an adjacent multi-isoform long noncoding RNA (lncRNA) named PTCHD1-AS (spanning ∼1 Mb), and a poorly characterized single-exon RNA helicase named DDX53 that is intronic to PTCHD1-AS. While the relationship between PTCHD1/PTCHD1-AS and ASD is being studied, the role of DDX53 has not been comprehensively examined, in part because there is no apparent functional murine ortholog. Through clinical testing, here, we identified 8 males and 2 females with ASD from 8 unrelated families carrying rare, predicted damaging or loss-of-function variants in DDX53. Additionally, we identified a family consisting of a male proband and his affected mother with high-functioning autism, both harboring a gene deletion involving DDX53 and exons of the noncoding RNA PTCHD1-AS. Then, we examined databases, including the Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, as well as population controls. We identified 26 additional individuals with ASD harboring 19 mostly maternally inherited, rare, damaging DDX53 variations, including two variants detected in families from the original clinical analysis. Our findings in humans support a direct link between DDX53 and ASD, which will be important in clinical genetic testing. These same autism-related findings, coupled with the observation that a functional orthologous gene is not found in mice, may also influence the design and interpretation of murine modeling of ASD.

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20. Vivanti G, Lee WL, Ventimiglia J, Tao S, Lyall K, Shea LL. Prevalence of Dementia Among US Adults With Autism Spectrum Disorder. JAMA Netw Open;2025 (Jan 2);8(1):e2453691.

This cohort study evaluates the prevalence of dementia diagnoses among US adults with autism spectrum disorder. eng program support through a contracting position with the Pennsylvania Department of Human Services, Office of Developmental Programs, Bureau of Supports for Autism and Special Populations. No other disclosures were reported.

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