1. Angell AM, Wee CP, Deavenport-Saman A, Parchment C, Bai C, Solomon O, Yin L. Sleep Disorders and Constipation in Autistic Children and Youth: Who Receives Standard of Care Drug Treatments?. J Autism Dev Disord;2025 (Mar 15)

PURPOSE: The purpose of this retrospective cohort analysis was to investigate sex differences in receipt of standard of care sleep and constipation drug treatments among autistic children and youth with sleep disorder and constipation, respectively. METHODS: We used the data from the OneFlorida + Data Trust to analyze healthcare claims for 19,877 autistic patients with sleep disorder and 32,355 patients with constipation, ages 1 to 22. We used logistic regression to examine sex differences in receiving sleep and constipation treatments, and a multivariate logistic regression model to further assess sex differences in ever receiving sleep and constipation treatments, adjusting for age, race, ethnicity, and urbanicity. RESULTS: In our multivariate analysis, autistic girls with sleep disorder were 1.27 times more likely than boys to receive sleep treatment (p < 0.0001). Although autistic girls with constipation appeared to be 1.10 times more likely than boys to receive treatment, it was not significantly different after adjusting for demographic and socio-economic characteristics (p = 0.372). Older children were 1.09 times more likely than younger children to receive sleep treatment (p < 0.0001) and 1.07 times more likely to receive constipation treatment (p < 0.0001). CONCLUSION: We did not find sex differences among autistic children for treatment of constipation, but autistic girls with sleep disorder were significantly more likely to have ever received treatment, which could indicate that girls experience more significant sleep disorders.

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2. Dembo RS, Hong J, DaWalt LS, Mailick MR. Age-related trajectories of health and cognition in mothers of children with developmental disabilities: Longitudinal findings from two independent studies. Soc Sci Med;2025 (Mar 4);372:117912.

Developmental disabilities are a heterogenous group of disorders characterized by impairments in physical functioning, learning, language, behavior, and self-care (Zablotsky et al., 2019). Parenting a child with a developmental disability can be a profound source of stress, particularly for mothers. This atypical parenting experience can begin with the birth of the child, or soon thereafter, and continues over the life course, often extending six decades or more. However, there is limited research on the impact of this parenting role across the full adult life course – from mothers’ early years of parenting through older age. Here we draw on data from two separate studies, one a national study of mothers of children with a range of developmental conditions (n = 96) and the other a community study of mothers of children with autism (n = 391). We used an accelerated longitudinal design to estimate mothers’ trajectories of health, mental health, and cognitive functioning beginning in their 20s and extending until their 80s or beyond, and conducted a series of cohort and sensitivity analyses. Together, the results of analyses of these two studies revealed very similar patterns across a number of important outcomes. The inclusion in one of the studies of a nationally representative comparison group of mothers whose children did not have disabilities (n = 1,181) indicated that after around age 65, aging in mothers of children with developmental disabilities differed from the norm, suggesting the ‘wear-and-tear’ effects of this common form of stressful parenting.

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3. Engels B, Bloemen MAT, Felius R, Damen K, Bolster EAM, Wittink H, Engelbert RHH, Gorter JW. Monitoring of child-specific activities in ambulatory children with and without developmental disabilities. BMC Pediatr;2025 (Mar 15);25(1):193.

BACKGROUND: Pediatric healthcare professionals facilitate children to enhance and maintain a physically active lifestyle. Activity monitors (AM) can help pediatric healthcare professionals assess physical activity in everyday life. However, validation research of activity monitors has often been conducted in laboratories and insight into physical activity of children in their own everyday environment is lacking. Our goal was to study the criterion validity of a prototype AM (AM-p) model in a natural setting. METHODS: Cross-sectional community-based study with ambulatory children (2-19 years) with and without developmental disability. Children wore the AM-p on the ankle and were filmed (gold standard) while performing an activity protocol in a natural setting. We labelled all videos per 5-second epoch with individual activity labels. Raw AM-p data were synchronized with activity labels. Using machine learning techniques, activity labels were subdivided in three pre-defined categories. Accuracy, recall, precision, and F1 score were calculated per category. RESULTS: We analyzed data of 93 children, of which 28 had a developmental disability. Mean age was 11 years (SD 4.5) with 55% girls. The AM-p model differentiated between ‘stationary’, ‘cycling’ and ‘locomotion’ activities with an accuracy of 82%, recall of 78%, precision of 75%, and F1 score of 75%, respectively. Children older than 13 years with typical development can be assessed more accurately than younger children (2-12 years) with and without developmental disabilities. CONCLUSION: The single ankle-worn AM-p model can differentiate between three activity categories in children with and without developmental disabilities with good accuracy (82%). Because the AM-p can be used for a heterogenous group of ambulatory children with and without developmental disabilities, it may support the clinical assessment for pediatric healthcare professionals in the future.

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4. Gao P, Wu J, Chang L, Jiang Z, Cui Y, Fan A, Ren S, Fu W, Xia S, Wei S, Ye D, Fang X. The impact of autistic traits on non-suicidal self-injury behavior among vocational high school students: A moderated mediation model. J Psychiatr Res;2025 (Mar 15);184:447-456.

BACKGROUND: Non-suicidal self-injury (NSSI) is a growing public health concern, yet its prevalence among vocational high school students is underexplored. The relationships between autistic traits, sleep patterns, and life satisfaction in relation to NSSI remain poorly understood. METHODS: This cross-sectional study was conducted on 10,252 vocational high school students with an average age of 20.1 from June 2022 to June 2023. Utilizing the PROCESS 3.4.1 macro in SPSS, analyses were performed to investigate the potential mediation of sleep disturbances in the relationship between autistic traits and non-suicidal self-injury behavior. Furthermore, we investigated the moderating effect of life satisfaction on this relationship. RESULTS: 8.2 % of vocational high school students in this study showed signs of NSSI issues. We found that sleep problems partially mediated the relationship between autistic traits and NSSI, accounting for 36.37 % of the mediation effect. Lastly, life satisfaction played a regulatory role in both direct and indirect paths of the aforementioned mediating model, with the mediation model remaining valid. CONCLUSION: Among vocational high school students, the prevalence of NSSI is notable, with high autistic traits influencing the development of NSSI by impacting sleep. Furthermore, life satisfaction plays a modifying role in this pathway.

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5. Leadbitter K, Langhorne S, Smallman R, Chu P, Ellis C, Harrison L, Hutton T, Butter C, Goldie C, James K, Hackett L, Dunkerley A, Bee P, Shields G, Davies L, Emsley R, Green J. Clinical effectiveness of an online psychoeducational and psychotherapeutic programme for caregivers of children newly diagnosed as autistic: a parallel, assessor-masked, randomised controlled trial in the UK (REACH-ASD). Lancet Psychiatry;2025 (Apr);12(4):289-302.

BACKGROUND: Caregivers of autistic children experience particularly poor levels of mental health and increased caregiving complexities. Proactive post-diagnostic family support is recommended but is inconsistently implemented, largely not evidence based, and does not directly address caregiver mental health. This study aimed to test the clinical effectiveness of the Empower-Autism programme plus treatment as usual versus the usual local post-diagnostic psychoeducation offer plus treatment as usual on caregiver mental health at the 52-week follow-up. METHODS: We did a prospective, multicentre, two-parallel-group, randomised controlled superiority trial of the Empower-Autism programme. Empower-Autism is a group-based, manualised, post-diagnostic programme designed to improve the mental health of caregivers of newly diagnosed autistic children. The programme combines autism psychoeducation and psychotherapeutic components based on Acceptance and Commitment Therapy and was delivered online via videoconferencing. Participants were recruited from 11 North-West England autism diagnostic or intervention centres and were parents or primary caregivers of children aged 2-15 years given an autism diagnosis within the past 12 months. Exclusion criteria were insufficient English language skills, significant learning disability, hearing or visual impairment, or psychiatric condition in caregiver and significant current family safeguarding concerns. Participants were randomly assigned to the intervention or treatment as usual (2:1), stratified by centre. Assessors were masked to group assignment but participants were not. The primary outcome was caregiver mental health assessed by the General Health Questionnaire-30 at 52 weeks. All outcomes were analysed following an intention-to-treat approach using linear mixed models on available cases in the first instance, which resulted in a modified intention-to-treat set due to missing data. Sensitivity analyses on multiply imputed data reflected the full intention-to-treat set. People with lived experience were involved in the trial across all stages. The trial was prospectively registered (ISRCTN 45412843) on Sept 11, 2019, and is complete. FINDINGS: Between Sept 16, 2020 and April 14, 2022, 835 potential participants were referred and screened, 384 provided consent, and 379 caregivers were recruited, 255 of whom were randomly assigned to the intervention group and 124 to the treatment as usual group. 333 (88%) participants were female and 46 (12%) were male, with a mean age of 40·6 years (SD 7·3; range 23-69). 294 (78%) of the 379 caregivers were White British, 18 (5%) were White Other, 12 (3%) were Mixed or of multiple ethnicity, 32 (8%) were Asian or Asian British, 16 (4%) were Black or Black British, six (2%) were from any other ethnic group, and one (<1%) had missing ethnicity data. 267 (70%) index children were male, 111 (29%) were female, and one (<1%) was non-binary or other, with a mean age 8·9 years (SD 3·5; range 2·0-16·0). In the available case analysis set (n=319) reflecting a modified intention-to-treat set due to missing data, participants randomly assigned to Empower-Autism had improved mental health at 52 weeks compared with those randomly assigned to treatment as usual (General Health Questionnaire-30 mean difference -4·95 [95% CI -8·21 to -1·68], p=0·0030). 181 adverse events (116 in the Empower-Autism group and 65 in the treatment as usual group) and 15 serious adverse events (nine in the Empower-Autism group and six in the treatment as usual group) were reported; none were deemed to be related to the study intervention. The most common adverse events concerned significant deteriorations in the mental health of caregiver participants or index children and other serious personal issues potentially affecting caregiver mental health. INTERPRETATION: To our knowledge, this is the first fully powered trial to show a statistically and clinically significant sustained effect on mental health in caregivers of newly diagnosed autistic children. In the context of the considerable clinical need in this area, we recommend the use of the Empower-Autism programme to clinicians and policy makers. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

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6. Li H, Chen Y, Qiu Y. Oxytocin lipidation expanding therapeutics for long-term reversal of autistic behaviors in rats. Int J Pharm;2025 (Mar 15);672:125299.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and repetitive, stereotyped behaviors. There is no universally effective pharmacological treatment targeting its core symptoms.Oxytocin, an endogenous polypeptide known as the « social hormone », has shown potential in improving emotional recognition and social interactions in individuals with ASD. However, its clinical application has been limited due to its short half-life and poor blood-brain barrier penetration. To address these challenges, we utilized peptide lipidation technology to enhance the pharmacokinetic properties and brain bioavailability of oxytocin. A series of lipidated oxytocin analogs was designed and synthesized, exhibiting superior brain distribution and pharmacokinetic profiles in valproic acid-induced autistic rat models compared to unmodified oxytocin. Among theseanalogs, C16-modified oxytocin (C16-OT), administered intrathecally, achieved the most extensive brain distribution with limited presence in the blood, resulting in long-lasting improvements in autistic behaviors. These improvements, including enhanced social behaviors and reduced stereotypical actions, were sustained for up to 42 days, contrasting with the brief effects typically reported in previous studies. Furthermore, a comparison of administration routes revealed that intrathecal injection achieved higher brain concentrations and more prolonged social behavioral improvements than intranasal delivery. These findings provide robust preclinical evidence that C16-OT, through optimized lipidation and intrathecal delivery, offers sustained central nervous system activity and significant, long-term reversal of social behavioral deficits in rats with autism.

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7. Page SD, Clark L, Souders MC, Pinto-Martin JA, Deatrick JA. Family management of common sleep disturbances among children with autism: Implications for pediatric nursing research and practice. J Pediatr Nurs;2025 (Mar 15);82:160-169.

BACKGROUND: Sleep disturbances are common among children with autism spectrum disorder (ASD) and can negatively impact the health and wellbeing of the child, caregiver, and family. Nurses are well-positioned to support families of children with ASD to improve sleep. DESIGN & PURPOSE: In this mixed methods study, we leveraged an existing dataset to 1) characterize qualitative descriptions of sleep disturbances experienced by children (4-10y) with ASD, 2) examine the convergence of qualitative descriptions of sleep disturbances with quantitative scores on the Children’s Sleep Habits Questionnaire (CSHQ), and 3) explore strategies used to manage bedtime and sleep disturbances. RESULTS: In this sample (n = 30), 70 % of caregivers described that their child had one or more sleep disturbances, with night wakings (43.3 %), bedtime resistance (30 %), and sleep anxiety (30 %) being most common. Qualitative descriptions largely converged with the CSHQ scores; however, in 20 % of cases, the caregiver reported no concerns about sleep while the CSHQ score indicated a clinically significant sleep problem. Management of bedtime and sleep disturbances required significant effort and balancing of multiple domains, including the child’s sleep needs, the sleep needs of the caregiver and other family members, the child’s sleep environment preferences and daytime activities that promote or disrupt sleep. CONCLUSION & IMPLICATIONS TO PRACTICE: Sleep disturbances are prevalent, despite efforts to implement bedtime routines and manage sleep disturbances. Pediatric nurses play an integral role in screening for sleep disturbances, educating families, and providing guidance for implementing behavioral and environmental interventions. Implications for clinical practice and future research are discussed.

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8. Rynard KM, Han K, Wainberg M, Calarco JA, Lee HO, Lipshitz HD, Smibert CA, Tripathy SJ. ASiDentify (ASiD): A Machine Learning Model to Predict New Autism Spectrum Disorder Risk Genes. Genetics;2025 (Mar 15)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects nearly 3% of children and has a strong genetic component. While hundreds of ASD risk genes have been identified through sequencing studies, the genetic heterogeneity of ASD makes identifying additional risk genes using these methods challenging. To predict candidate ASD risk genes, we developed a simple machine learning model, ASiDentify (ASiD), using human genomic, RNA- and protein-based features. ASiD identified over 1,300 candidate ASD risk genes, over 300 of which have not been previously predicted. ASiD made accurate predictions of ASD risk genes using six features predictive of ASD risk gene status, including mutational constraint, synapse localization and gene expression in neurons, astrocytes and non-brain tissues. Particular functional groups of proteins found to be strongly implicated in ASD include RNA-binding proteins and chromatin regulators. We constructed additional logistic regression models to make predictions and assess informative features specific to RNA-binding proteins, including mutational constraint, or chromatin regulators, for which both expression level in excitatory neurons and mutational constraint were informative. The fact that RNA-binding proteins and chromatin regulators had informative features distinct from all protein-coding genes, suggests that specific biological pathways connect risk genes with different molecular functions to ASD.

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9. Sun YQ, Huang XX, Guo W, Hong C, Ji J, Zhang XY, Yang J, Hu G, Sun XL. IFN-γ signaling links ventriculomegaly to choroid plexus and ependyma dysfunction following maternal immune activation. J Neuroinflammation;2025 (Mar 15);22(1):83.

Maternal immune activation (MIA) is a principal environmental risk factor contributing to autism spectrum disorder (ASD) and can be causally linked to ASD symptoms. In our study, we found that MIA triggered by poly (I: C) injection caused ventriculomegaly in offspring due to the dysfunction of the choroid plexus (Chp) and ependyma. We subsequently identified a sustained enhancement of interferon-γ (IFN-γ) signaling in the brain and serum of MIA offspring. Further study revealed that increased IFN-γ signaling could disrupt the barrier function of Chp epithelial cells by activating macrophages, and suppress the differentiation of primary ependymal cells via the signal transducer and activator of transcription 1/3 signaling. The effects of MIA on the offspring were mitigated by administration of IFNGR-blocking antibody in pregnant dams, while systemic maternal administration of IFN-γ was sufficient to mimic the effect of MIA. Overall, our findings revealed that ventriculomegaly caused by IFN-γ signaling could be a critical factor in compromising fetal brain development in MIA-induced ASD and provide a mechanistic framework for the association between maternal inflammation and abnormal development of ventricles in the offspring.

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10. Tamada K, Takumi T. Neurodevelopmental impact of CNV models in ASD: Recent advances and future directions. Curr Opin Neurobiol;2025 (Mar 15);92:103001.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication impairments and restricted, repetitive behaviors. ASD exhibits a strong genetic basis, with rare and common genetic variants contributing to its etiology. Copy number variations (CNVs), deletions or duplications of chromosomal segments, have emerged as key contributors to ASD risk. Rare CNVs often demonstrate large effect sizes and can directly cause ASD, while common variants collectively exert subtle influences. Recent advances have identified numerous ASD-associated CNVs, including recurrent loci such as 1q21.1, 2p16.3, 7q11.23, 15q11.2, 15q11-q13, 16p11.2 and 22q11.2. Mouse models carrying these CNVs have provided profound insights into the underlying neurobiological mechanisms. Recent studies integrating transcriptomic, proteomic, and functional imaging approaches have revealed alterations in synaptic function, neuronal differentiation, myelination, metabolic pathways, and circuit connectivity. Notably, investigations leveraging conditional knockout models, high magnetic field MRI, and single-cell analyses highlight disruptions in excitatory-inhibitory balance, white matter integrity, and dynamic gene regulatory networks. Parallel human-based approaches, including iPSC-derived neurons, cerebral organoids, and large-scale single-nucleus sequencing, are combined with animal model data. These integrative strategies promise to refine our understanding of ASD’s genetic architecture, bridging the gap between fundamental discoveries in model organisms and clinically relevant biomarkers, subtypes, and therapeutic targets in humans. This review summarizes key findings from recent CNV mouse model studies and highlights emerging technologies applied to human ASD samples. Finally, we outline prospects for translating findings from mouse studies to humans. By illuminating both unique and convergent genetic mechanisms, these advances offer a critical framework for unraveling etiological complexity in ASD.

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11. Turecki SC, Payne TW. Peer Acceptance of Autistic College Students. J Autism Dev Disord;2025 (Mar 15)

As autistic young adults increasingly enter into higher education, many are faced with difficult social adjustment (e.g., making friends, acquiring social support) in college (McLeod et al. McLeod et al., Journal of Autism and Developmental Disorders 49:2320-2336, 2019). Understanding peer acceptance of autistic college students is critical for community growth toward an equitable education experience. Predictors of autism acceptance, such as knowledge of autism, quantity and quality of experience with autism, and family relationships were explored. Acceptance of autism was assessed with a standardized vignette describing behavior of a hypothetical peer on campus, with no disclosure of a diagnosis (Nevill & White (Nevill and White, Journal of Autism and Developmental Disorders 41:1619-1628, 2011). Following the reading, participants made ratings on statements regarding willingness to engage and interact with the hypothetical case. Results revealed a positive correlation between raters’ quality of past experience with autism and their acceptance of a hypothetical autistic peer. Knowledge and quantity of experience did not predict acceptance. Having an autistic family member was also not associated with higher acceptance, however, the closeness of relationships with diagnosed family members was positively correlated with acceptance. These findings promote the idea that increasing acceptance of autistic college students could be facilitated through high quality social experiences with autistic individuals.

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12. Wannapaschaiyong P, Vivattanasinchai T, Wongkwanmuang A. Predictors of successful Picture Exchange Communication System training in children with communication impairments: insights from a real-world intervention in a resource-limited setting. BMJ Paediatr Open;2025 (Mar 13);9(1)

BACKGROUND: Children with communication impairments-such as autism spectrum disorder or global developmental delay-face significant challenges affecting their emotional and behavioural development. The Picture Exchange Communication System (PECS) is an augmentative communication tool designed to enhance their skills. However, its effectiveness can vary in resource-limited settings. This study aimed to identify predictors of successful PECS training among children with communication impairments in such environments. METHODS: This retrospective study analysed records of 61 children with communication impairments who underwent PECS training at Siriraj Hospital in Bangkok, Thailand, from 2020 to 2023. Success was defined as achieving PECS phase 3 proficiency and a Clinical Global Impression-Improvement score of 1-3 after 1 year. Logistic regression identified predictors of successful outcomes based on demographic, clinical, family and training-related factors. RESULTS: After 1 year, 46% (28 out of 61) of the children achieved successful PECS outcomes. Significant predictors of success were lower severity of communication impairment (Clinical Global Impression-Severity ≤4; adjusted OR= 15.24, p = 0.002), higher frequency of PECS sessions (>6 times per year; OR = 9.11, p = 0.010), higher family income (≥20,000 baht per month; OR = 9.83, p = 0.024) and frequent home practice (≥3 times per week; OR = 7.02, p = 0.066). CONCLUSIONS: In resource-limited settings, factors such as severity of impairment, intensity of intervention, socioeconomic status and caregiver involvement significantly influence the success of PECS training. Tailored interventions and strategic resource allocation are crucial to optimise communication outcomes for these children.

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13. Zhang Z, Yu J, Li Q, Zhao Y, Tang L, Peng Y, Liu Y, Gan C, Liu K, Wang J, Chen L, Luo Q, Qiu H, Ren H, Jiang C. Unraveling the causal pathways of maternal smoking and breastfeeding in the development of neuropsychiatric disorders: A Mendelian randomization perspective. J Affect Disord;2025 (Mar 15);373:35-43.

BACKGROUND: Maternal smoking around birth (MSAB) and early-life breastfeeding (BAB) represent critical factors that may exert enduring effects on neuropsychiatric health. Although previous research has examined these exposures separately, the combined impact of both on disorders such as ADHD, ASD, BD, MDD, ANX, and SCZ remains unclear. This study aims to evaluate the causal relationships between MSAB and BAB and the risk of developing these neuropsychiatric disorders through Mendelian randomization (MR) analysis. METHODS: A two-sample MR analysis was conducted to investigate the potential causal effects of MSAB and BAB on a range of neuropsychiatric disorders. Genetic variants associated with MSAB and BAB were obtained from genome-wide association studies (GWAS), while summary data for neuropsychiatric disorders were gathered from large GWAS consortia. The primary MR analysis was conducted using the inverse-variance weighted (IVW) method, with additional sensitivity analyses performed to confirm the robustness of the findings. A False Discovery Rate (FDR) correction was applied to control for the issue of multiple comparisons and reduce the risk of Type I errors. RESULTS: The IVW analysis indicated that there were significant associations between MSAB and an increased risk of the following conditions: The IVW analysis indicated significant associations between MSAB and an increased risk of ADHD (odds ratio [OR] = 5.36, 95 % confidence interval [CI] = 2.58-7.63, p-value for false discovery rate [PFDR] = 0.004) and major depressive disorder (MDD) (OR = 1.92, 95 % CI = 1.29-2.88, PFDR = 0. Furthermore, significant associations were observed between MSAB and an increased risk of bipolar disorder (BD) (OR = 6.33, 95 % CI = 1.56-8.73, PFDR = 0.020), anxiety disorders (ANX) (OR = 1.03, 95 % CI = 1.00-1.05, PFDR = 0.039), and attention deficit hyperactivity disorder (ADHD) (OR = 5.36, 95 % CI = 2.58-7.63, PFDR = 0.004). No significant associations were identified between MSAB and Autism Spectrum Disorder (ASD) or Schizophrenia (SCZ). In contrast, the results indicated that BAB was associated with a protective effect against ADHD (OR = 0.17, 95 % CI = 0.04-0.63, PFDR = 0.025), MDD (OR = 0.26, 95 % CI = 0.12-0.58, PFDR = 0.006), and ANX (OR = 0.96, 95 % CI = 0.49-0.99, PFDR = 0.030). No significant effects of BAB were observed for ASD, BD, or SCZ. CONCLUSIONS: This study shows that maternal smoking around the time of birth increases the risk of attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), bipolar disorder (BD), and anxiety disorders (ANX). In contrast, breastfeeding during infancy offers protective benefits against ADHD, MDD, and ANX. These findings underscore the vital importance of maternal health behaviours during the perinatal and infant feeding periods. They also highlight the need for targeted public health interventions aimed at reducing the risk of neuropsychiatric disorders.

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