1. Al-Ayadhi LY, Elamin NE, Madani A, Al-Ghamdi F, Al-Ghamdi HA, Halepoto DM. Examining the Prevalence, Characteristics, and Potential Links Between Skin Disorders and Autism Spectrum Disorder (ASD). J Clin Med. 2025; 14(2).

Background: Increasing evidence indicates that skin disorders may contribute to an increased risk of autism spectrum disorder (ASD). They can affect the quality of life, and they have an impact on social isolation, behavioral problems, cognitive scores, and some subscales of ASD. Methods: This study was an online questionnaire-based, observational, and cross-sectional study conducted during the period from August 2022 through January 2023 to examine dermatological manifestations among ASD individuals compared to controls. Descriptive and non-parametric tests were used for data analysis. Results: A total of 363 individuals with skin diseases were interviewed during the study period. In total, 189 (52.1%) of participants were autistic and 174 (47.9%) were controls. Asthma, anxiety, depression, and autoimmune disease were persistent in the ASD group compared to the controls (p < 0.001). The results also show that skin, food, and respiratory allergies were statistically significantly associated with ASD (50%, 22.2%, 14.8%, respectively) compared to the controls (26.4%, 10.3%, 7.5%, respectively) (p < 0.05). The most prevalent disease in the controls was eczema (15.5%), followed by dry skin (14.9%) and acne (10.3%). These diseases showed a statistically significant association with ASD compared to the controls (p < 0.0001). Conclusions: Our findings indicate that atopic disorders and comorbidities, including eczema, asthma, and allergies, are significantly associated with ASD. A large population-based study is warranted to clarify the prevalence of skin disorders among individuals with ASD, coupled with the study of the association between skin disorders and comorbidities to determine the relationship precisely.

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2. Aller TB, Kelley HH, Juhasz A, Covington B. COVID-19 health distress among autistic adults: Does psychological flexibility explain effects of health distress on mental health concerns?. Autism. 2025: 13623613241313403.

What is already known?In the United States, the COVID-19 Pandemic caused many autistic adults to be fearful and worried about their health. There is a lot of research that says that when autistic adults experience health distress it can worsen their mental health. We do not know, however, what might explain how experiencing health distress negatively affects mental health. Because of this, our participatory action research team wanted to understand if there are strengths-based processes that help us understand the relationship between health distress and mental health concerns.What does this paper add?We examined among 281 autistic adults how a strengths-based construct from acceptance and commitment therapy called psychological flexibility might explain the relationship between health distress and mental health concerns. We found that for adults that had more values progress, doing the things that mattered to them, was associated with better mental health even while experiencing health distress. We also found that values obstruction, getting stuck on uncomfortable thoughts and feelings and trying to avoid them, explained worse mental health for autistic adults experiencing health distress.Implications for research and practice?The findings of this study provide initial support that psychological flexibility can explain the relationship between health distress and mental health concerns among autistic adults. Interventions that seek to improve psychological flexibility, like acceptance and commitment therapy, might be useful in improving autistic adults’ mental health while they are experiencing health distress.

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3. Beg M, McMorris CA, Smyth K, Buchhalter J, Dewey D. Transdiagnostic Predictors of Health-Related Quality of Life in Children with Autism and Epilepsy: A Cross-Sectional Study. J Clin Med. 2025; 14(2).

Background/Objectives: Our understanding of the transdiagnostic factors that influence health-related quality of life (HRQOL) in individuals with neurodivergent conditions is very sparse and highly siloed by diagnosis labels. Research on transdiagnostic predictors of HRQOL across neurodevelopmental conditions is needed to enable care models that address shared needs of neurodivergent individuals beyond diagnostic boundaries. Our objective was to identify transdiagnostic factors associated with HRQOL in children with autism, epilepsy, or comorbid autism/epilepsy. Methods: This cross-sectional study included 37 autistic and/or epileptic children (mean age = 9.2; SD = 3.9; boys = 28). Parents provided sociodemographic information and completed the following measures: Social Communication Questionnaire (measure of severity of autistic symptoms); Parenting Stress Index, Fourth Edition; Pediatric Quality of Life Inventory; and the Behavioral Assessment System for Children, Third Edition. Child intellectual functioning was measured using age-appropriate scales: the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition: Canadian or the Wechsler Intelligence Scale for Children-Fifth Edition: Canadian. Results: Higher autistic symptom severity (OR = 0.851 95% CI: 0.732-0.988, p = 0.034) and parenting stress (OR = 0.687 95% CI: 0.493-0.959, p = 0.027) were associated with poorer HRQOL. Full Scale IQ and adaptive skills showed trend level associations with HRQOL. Sociodemographic factors including maternal education, child sex, and child age as well as child diagnosis were not associated with HRQOL. Conclusions: In this transdiagnostic sample of children, autism symptom severity and parenting stress were shared predictors of HRQOL. Interventions targeting child autistic symptoms and parents’ levels of stress could result in improved HRQOL in neurodivergent populations.

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4. Bo M, Carta A, Cipriani C, Cavassa V, Simula ER, Huyen NT, Phan GTH, Noli M, Matteucci C, Sotgiu S, Balestrieri E, Sechi LA. HERVs Endophenotype in Autism Spectrum Disorder: Human Endogenous Retroviruses, Specific Immunoreactivity, and Disease Association in Different Family Members. Microorganisms. 2024; 13(1).

Increasing evidence indicates that human endogenous retroviruses (HERVs) are important to human health and are an underexplored component of many diseases. Certain HERV families show unique expression patterns and immune responses in autism spectrum disorder (ASD) patients compared to healthy controls, suggesting their potential as biomarkers. Despite these interesting findings, the role of HERVs in ASD needs to be further investigated. In this review, we discuss recent advances in genetic research on ASD, with a particular emphasis on the implications of HERVs on neurodevelopment and future genomic initiatives aimed at discovering ASD-related genes through Artificial Intelligence. Given their pro-inflammatory and autoimmune characteristics, the existing literature suggests that HERVs may contribute to the onset or worsening of ASD in individuals with a genetic predisposition. Therefore, we propose that investigating their fundamental properties could not only improve existing therapies but also pave the way for new therapeutic strategies.

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5. Campanella S, Volpe T, Safar Y, Lunsky Y. « They need to speak a language everyone can understand »: Accessibility of COVID-19 vaccine information for Canadian adults with intellectual and developmental disabilities. Vaccine. 2025; 45: 126618.

Accessible vaccine information is one vital component of effective vaccination programs, however, there is limited research that explores how people with disabilities engage with public health messaging. This study aimed to understand how adults with intellectual and developmental disabilities (IDD) and their caregivers navigated Canada’s public health communications regarding COVID-19 vaccines. A national survey on the accessibility of vaccine information was conducted in the spring and summer of 2022. Surveys were completed by 208 adults with IDD, 102 family caregivers and friends, and 54 staff. Quantitative data were analyzed descriptively, and descriptive qualitative content analysis was applied to open-ended survey responses. Vaccine information was difficult to understand and was not accessible to many people with IDD and their caregivers. Approximately 75 % of adults with IDD found COVID-19-related information challenging to comprehend, followed by 69 % of family/friends and 56 % of staff. All three groups indicated they felt overwhelmed by the large quantity of information they had to navigate (adults with IDD, 72 %; family/friends, 65 %; staff, 70 %) and experienced difficulties such as finding trustworthy sources and identifying vaccine misinformation and disinformation. Respondents offered recommendations to improve public health messaging and the accessibility of future vaccine campaigns. Our study explored the experiences of Canadian adults with IDD and caregivers while navigating COVID-19 vaccine information, revealing significant barriers. To address these barriers and improve vaccine uptake, public health communications must ensure accessibility throughout every stage of immunization, including education campaigns, appointment booking, vaccination appointment, and aftercare services. Recommendations include using Easy Read language and multiple formats, supporting caregivers and community groups, and enlisting trusted community messengers to disseminate accurate information and build confidence among adults with IDD and their caregivers.

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6. Campbell K, Neul JL, Lieberman DN, Berry-Kravis E, Benke TA, Fu C, Percy A, Suter B, Morris D, Carpenter RL, Marsh ED, von Hehn J. A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome. J Neurodev Disord. 2025; 17(1): 4.

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy. DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy. METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment. Ketamine was dosed twice daily at 0.75 mg/kg/dose (Cohort 1) or 1.5 mg/kg/dose (Cohort 2). An independent safety monitoring committee evaluated safety and approved proceeding to the next dose cohort. Caregivers, participants, outcome assessors, and study staff except pharmacists were blinded to allocation. The primary endpoint was safety and tolerability. Exploratory efficacy endpoints included change in clinician- and caregiver-rated measures of RTT features, brain activity on electroencephalography, and wearable biosensors to measure respiration, heart rate, sleep, and activity. RESULTS: Twenty-three participants enrolled (11 in Cohort 1, 12 in Cohort 2) from 3/12/2019-11/22/2021. One participant was excluded from analysis due to not meeting inclusion criteria on blinded review prior to analysis. One participant was withdrawn from the study due to an adverse event (vomiting) after the first dose of ketamine. Although planned for four dose cohorts, the trial was stopped after Cohort 2 due to enrollment challenges associated with the COVID-19 pandemic. Ketamine was safe and tolerated in both cohorts, with 1 related treatment emergent adverse event of vomiting. No difference was observed in efficacy between ketamine and placebo. Electroencephalography showed the expected increase in high frequency power with ketamine. CONCLUSIONS: Short-term, low-dose oral ketamine was safe and well tolerated in girls with RTT. No clinical efficacy of ketamine in treating symptoms of RTT was observed with 5 days of treatment, despite electroencephalography evidence of ketamine target engagement during the first dose. Further studies are needed to evaluate safety and efficacy of higher dose and longer exposure to ketamine in RTT. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT03633058.

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7. Curley K, Hughes R, Kotera Y. Stressful but Not Unhappy: A Review of the Positive Aspects of Parenting a Child with Autism Spectrum Disorder. Children (Basel). 2025; 12(1).

This review aimed to identify and synthesise the evidence for the positive aspects of parenting a child with autism spectrum disorder (ASD). To date, ASD parental research has predominantly focused on the negative aspects; parents and carers are left uninformed of how to strengthen their positive mental wellbeing. Three electronic databases-PubMed, Scopus, and Web of Science -were searched for literature reporting positive aspects of parenting a child with ASD, published between January 2013 and December 2023. The PRISMA 2020 checklist was used for reporting. Two hundred and fifty-four articles were retrieved from the databases. After title/abstract screening (n = 213) and full-text reviews (n = 32), six papers were included (n = 6). Sixteen positive aspects of parenting a child with ASD were identified and grouped into three themes: joyful moments, journey to resilience, and social connection. These three themes are eudaimonic wellbeing constructs and often under-represented in ASD parental studies. Focusing on joyful moments, building resilience through the parenting journey, and finding support and connection with others in similar situations can support the mental wellbeing of parents and carers of children with ASD. Future research is needed to further evaluate the positive aspects of parenting a child with ASD.

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8. Di Giorgio E, Benavides-Varela S, Porru A, Caviola S, Lunghi M, Rigo P, Mioni G, Calignano G, Annunziata M, Valenza E, Liani V, Beghetti F, Spolaor F, Bettella E, Polli R, Sawacha Z, Murgia A. Neurobehavioral Outcomes Relate to Activation Ratio in Female Carriers of Fragile X Syndrome Full Mutation: Two Pediatric Case Studies. Int J Mol Sci. 2025; 26(2).

Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder that causes a range of developmental problems including cognitive and behavioral impairment and learning disabilities. FXS is caused by full mutations (FM) of the FMR1 gene expansions to over 200 repeats, with hypermethylation of the cytosine-guanine-guanine (CGG) tandem repeated region in its promoter, resulting in transcriptional silencing and loss of gene function. Female carriers of FM are typically less impaired than males. The Activation Ratio (AR), the fraction of the normal allele carried on the active X chromosome, is thought to play a crucial modifying role in defining phenotype severity. Here, we compare the cognitive, neuropsychological, adaptive, and behavioral profile of two FXS girls (10 and 11 years old) with seemingly identical FMR1 genotypic profile of FM but distinctive AR levels (70% vs. 30%). A multi-method protocol, combining molecular pathophysiology and phenotypical measures, parent reports, lab-based tasks, gait analyses, and eye-tracking was employed. Results showed that lower AR corresponds to worse performances in most (cognitive, neuropsychological, adaptive, behavioral, social, mathematical skills), but not all the considered areas (i.e., time perception and gait analysis). These observations underscore the importance of AR as a phenotypic modifying parameter in females affected with FXS.

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9. Długosz A, Wróblewski M, Błaszak B, Szulc J. The Role of Nutrition, Oxidative Stress, and Trace Elements in the Pathophysiology of Autism Spectrum Disorders. Int J Mol Sci. 2025; 26(2).

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, alongside repetitive behaviors, and atypical sensory-motor patterns. The growing prevalence of ASD has driven substantial advancements in research aimed at understanding its etiology, preventing its onset, and mitigating its impact. This ongoing effort necessitates continuous updates to the body of knowledge and the identification of previously unexplored factors. The present study addresses this need by examining the roles of nutrition, oxidative stress, and trace elements in the pathophysiology of ASD. In this review, an overview is provided of the key dietary recommendations for individuals with ASD, including gluten-free and casein-free (GFCF) diets, ketogenic diets (KDs), and other nutritional interventions. Furthermore, it explores the involvement of oxidative stress in ASD and highlights the significance of trace elements in maintaining neuropsychiatric health. The impact of these factors on molecular and cellular mechanisms was discussed, alongside therapeutic strategies and their efficacy in managing ASD.

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10. Esposito M, Piersanti C, Fadda R, Boitani M, Mazza M, Marrocco G. Oral Hygiene in Children with Autism: Teaching Self-Toothbrushing via Behavioural Intervention Including Parents. Children (Basel). 2024; 12(1).

BACKGROUND/OBJECTIVES: Children on the autism spectrum experience more oral hygiene issues than peers, and tooth-brushing behavior seems particularly challenging for them since it includes diverse skills and collaboration. In this study, the efficacy is explored of a behavioral intervention mediated by staff and parents in teaching self-brushing teeth in eight autistic children. First, we wanted to examine whether the intervention improved self-brushing teeth skills in a short-term period. Second, we evaluated the long-term outcomes of the intervention. Finally, we analyzed the individual differences which might predict better outcomes. METHODS: The training started during an ABA summer school with a supervised behavioral staff and lasted for eight sessions. The training package included several behavioral procedures such as prompting, fading, task analysis, chaining, differential reinforcement, direct instructions, visual aids, pictograms, and video modeling. According to a pre-and post-test design, we measured the frequency of independent self-brushing behaviors and interviewed the parents about the hygiene routines. RESULTS: The results indicate a significant improvement in children’s self-brushing teeth behavior and maintenance, where 33.7% of the steps were achieved by children at baseline and 77.5% at post-training, and with four children, 100%. The parent questionnaires reported significant improvement in autonomy of self-brushing and times a day dedicated to oral hygiene. The severity of symptoms, sensory hypersensitivity, and lower IQ levels of the children negatively correlated with the outcome. CONCLUSIONS: These results point to relevant practical suggestions for families and clinical staff to address oral hygiene in the autism population.

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11. Fang J, Kang SG, Huang K, Tong T. Integrating 16S rRNA Gene Sequencing and Metabolomics Analysis to Reveal the Mechanism of L-Proline in Preventing Autism-like Behavior in Mice. Nutrients. 2025; 17(2).

BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior. Effective interventions for the core autistic symptoms are currently limited. METHODS: This study employed a valproic acid (VPA)-induced mouse model of ASD to assess the preventative effects of L-proline supplementation on ASD-like behaviors. The method of 16S rRNA sequencing and untargeted metabolomics analyses were conducted to investigate the modulation of gut microbiota and gut metabolites by L-proline. RESULTS: The results indicated that L-proline supplementation significantly prevented ASD-like behavioral disorders, including alleviating social communication deficits and reducing repetitive behavior in the ASD mice. The 16S rRNA sequencing analysis revealed that L-proline regulated the composition and structure of gut microbiota. L-Proline supplementation enhances the abundance of the Verrucomicrobia at the phylum level and the Akkermansia at the genus level, while concurrently reducing the abundance of the Patescibacteria at the phylum level, as well as the Ileibacterium, Candidatus_Saccharimonas, and Lachnospiraceae_UCG-006 at the genus level in the VPA-induced mouse model for ASD. Additionally, the untargeted metabolomics results indicated that L-proline also modified the gut metabolite profiles. Functional analysis of the gut microbiota and KEGG pathway enrichment analysis of differential metabolites between the L-proline-supplemented and VPA groups corroborated that L-proline decreased pathways related to nucleotide metabolism, taurine and hypotaurine metabolism, and pyruvate metabolism, while increasing pathways involved in alpha-linolenic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. The integrative metabolomic and microbiome analyses showed strong connections between the gut metabolites and gut microbiota affected by L-proline. These findings suggest that the modulatory effects of L-proline on gut microbiota and its metabolites may play a crucial role in preventing autism in mice. CONCLUSIONS: These findings suggest that dietary L-proline may represent a viable, effective option for preventing the physiological and behavioral deficits associated with ASD in mice.

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12. Ferraro S, Saielli L, Biganzoli D, Tosi M, Guidi L, Longo R, Severino F, Carelli S, Rossi M, Pisciotta L, Ricci E, Brustia F, Verduci E, Zuccotti G, Mussap M, Cereda C. Amino Acid Patterns in Children with Autistic Spectrum Disorder: A Preliminary Biochemical Evaluation. Nutrients. 2025; 17(2).

BACKGROUND: The metabolism of plasma amino acid (AA) in children with autism spectrum disorder (ASD) has been extensively investigated, yielding inconclusive results. This study aims to characterize the metabolic alterations in AA profiles among early-diagnosed children with ASD and compare the findings with those from non-ASD children. METHODS: We analyzed plasma AA profiles, measured by ion exchange chromatography, from 1242 ASD children (median age = 4 years; 81% male). Additionally, we studied AA profiles from 488 children, matched for age and free of ASD (control group). Principal component and cluster analysis were employed to explore potential associations within the ASD group and to identify subgroups. RESULTS: We observed lower plasma levels of glutamine in children with ASD compared to non-ASD children (p < 0.001). Six essential, two conditionally essential, and four non-essential AA were found to be increased in children with ASD. The clustering analysis revealed two groups, labeled Neurological (NEU) and Nutritional (NUT), which included a majority of ASD children (94% and 78%, respectively). The NEU group exhibited high levels of taurine, aspartate, glutamic acid, and ornithine, while the NUT group showed elevated levels of branched-chain AA. CONCLUSIONS: In children with ASD, we identified some heterogeneous AA patterns that may serve as biochemical signatures of neurological impairment in some individuals, while in others they may indicate nutritional dysregulation.

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13. Ferrini L, Bartolini E, Mancini A, Tancredi R, Ferrari AR, Calderoni S. EEG Abnormalities and Phenotypic Correlates in Preschoolers with Autism Spectrum Disorder: A Single-Center Study. J Clin Med. 2025; 14(2).

Background: The literature suggests the existence of an association between autism spectrum disorders (ASDs) and subclinical electroencephalographic abnormalities (SEAs), which show a heterogeneous prevalence rate (12.5-60.7%) within the pediatric ASD population. The aim of this study was to investigate the EEG findings in a cohort of ASD preschoolers and their correlation with the phenotypic characteristics. Methods: We retrospectively reviewed data on 141 ASD preschoolers evaluated in a tertiary care university hospital over the period 2008-2018. All participants underwent at least one standard polygraphic electroencephalogram (EEG) and a clinical multidisciplinary assessment with standardized instruments. Results: 77 patients (55%) showed SEAs, which were mainly represented by epileptiform discharges (p < 0.00001), especially focal and multifocal (p = 0.010). Abnormal EEG (p = 0.035) and epileptiform discharges (p = 0.014) were associated with seizure onset and were predominant in sleep (p < 0.00001). Patients with abnormal tracing (p = 0.031) and slow abnormalities (p < 0.001) were significantly younger. ASD severity was not found to be correlated with EEG results, which showed a potential, albeit non-significant, association with some psychometric parameters. Very similar results were found when patients were divided according to sex. Conclusions: EEG abnormalities appear to correlate more with ASD internalizing, externalizing and emotional comorbidities, rather than with ASD core symptoms; larger samples are needed to further investigate this association.

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14. Forbes EJ, Tiego J, Langmead J, Unruh KE, Mosconi MW, Finlay A, Kallady K, Maclachlan L, Moses M, Cappel K, Knott R, Chau T, Sindhu VPM, Bellato A, Groom MJ, Kerestes R, Bellgrove MA, Johnson BP. Oculomotor Function in Children and Adolescents with Autism, ADHD or Co-occurring Autism and ADHD. J Autism Dev Disord. 2025.

Oculomotor characteristics, including accuracy, timing, and sensorimotor processing, are considered sensitive intermediate phenotypes for understanding the etiology of neurodevelopmental conditions, such as autism and ADHD. Oculomotor characteristics have predominantly been studied separately in autism and ADHD. Despite the high rates of co-occurrence between these conditions, only one study has investigated oculomotor processes among those with co-occurring autism + ADHD. Four hundred and five (n = 405; 226 males) Australian children and adolescents aged 4 to 18 years (M = 9.64 years; SD = 3.20 years) with ADHD (n = 64), autism (n = 66), autism + ADHD (n = 146), or neurotypical individuals (n = 129) were compared across four different oculomotor tasks: visually guided saccade, anti-saccade, sinusoidal pursuit and step-ramp pursuit. Confirmatory analyses were conducted using separate datasets acquired from the University of Nottingham UK (n = 17 autism, n = 22 ADHD, n = 32 autism + ADHD, n = 30 neurotypical) and University of Kansas USA (n = 29 autism, n = 41 neurotypical). Linear mixed effect models controlling for sex, age and family revealed that children and adolescents with autism + ADHD exhibited increased variability in the accuracy of the final saccadic eye position compared to neurotypical children and adolescents. Autistic children and adolescents demonstrated a greater number of catch-up saccades during step-ramp pursuit compared to neurotypical children and adolescents. These findings suggest that select differences in saccadic precision are unique to autistic individuals with co-occurring ADHD, indicating that measuring basic sensorimotor processes may be useful for parsing neurodevelopment and clinical heterogeneity in autism.

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15. Hendry A, Hulks V, Murphy S, Radford H, Smith S, Charman T, Mathers S, Rhodes S, Scerif G. Learning from the community: iterative co-production of a programme to support the development of attention, regulation and thinking skills in toddlers at elevated likelihood of autism or ADHD. Res Involv Engagem. 2025; 11(1): 7.

Programmes designed to support children with known, or increased likelihood of, autism or ADHD often focus on reducing behaviours central to a clinical diagnosis. However, supporting children to pursue their own goals and cope with everyday life through fostering executive function (EF) development, without enforcing neuro-normative assumptions, may be more acceptable to neurodivergent people, and more beneficial. The co-production process for this neurodiversity-affirming programme involved: Review of research priorities identified during published public-and-clinician consultations; iterative programme development through two pilot rounds with a general community sample; and consultation with stakeholders (parents with a connection to autism or ADHD, alongside early years specialists, psychologists and therapists) to check acceptability of the proposal, and refine the logic model and materials. The logic model for the resultant programme-Supporting Toddlers with a connection to autism or ADHD to develop strong Attention, Regulation and Thinking skills (START)-involves three mechanisms of change: The child has appropriate play-based opportunities to practise EF skills; Parenting behaviours linked to strong EFs are encouraged; Parents are empowered to improve environmental-fit for their child so that EF stressors are reduced. Children showing many autistic traits, or who have a close family member on the autism spectrum or having ADHD, are more likely than average to struggle with attention, regulation and thinking skills. This may lead to difficulties with mental health and independent living in later life. We aimed to create a parent-toddler programme that would help children with a connection to autism or ADHD to thrive, without pressuring them to act in a certain way. To do this we first reviewed the results of previous studies and community consultations, and identified how we could build on an existing parent support programme structure to meet the project goals. Next, we tried out our ideas with 18 families. Then, we asked nine parents with a connection to autism or ADHD (because they are neurodivergent themselves, and/or raising a neurodivergent child), and five professionals to help us improve the materials further. The end result is a programme called START (Supporting Toddlers with a connection to autism or ADHD to develop strong Attention, Regulation and Thinking skills). This 12-week group-based parent-toddler programme aims to foster children’s development in three ways: (1) Giving children opportunities to practise their skills through play and everyday activities (2) Creating a welcoming, accessible and non-judgemental space for parents to hear about and share ideas (3) Helping parents to identify ways to help their child feel calm, safe and supported. eng.

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16. Kanzari C, Hawani A, Ayed KB, Mrayeh M, Marsigliante S, Muscella A. The Impact of a Music- and Movement-Based Intervention on Motor Competence, Social Engagement, and Behavior in Children with Autism Spectrum Disorder. Children (Basel). 2025; 12(1).

BACKGROUND/OBJECTIVES: The main objective of this manuscript is to evaluate the effects of training, music, and movement intervention on motor functions, social engagement, and behaviors in autistic children. METHODS: Twenty-one children with a diagnosis of mild autism spectrum disorder (ASD), with an age range of 5-to-13 years, were divided into two groups: the experimental group (n = 10) and the control group (n = 11). All participants were examined before (T0) and after the intervention (T1) to evaluate their motor functions (Bruininks-Oseretsky Motor Performance Test (BOT-2)), maladaptive behavior (RCS (Response to Challenge Scale)), and enjoyment and engagement (PACES (Physical Activity Enjoyment Scale)). RESULTS: Statistical analysis showed that music and movement intervention significantly improved motor functions such as balance and bilateral coordination (p < 0.0001), social engagement (p = 0.002), and adaptive behaviors (p = 0.005) in children with ASD. Our research supports the feasibility of music and movement intervention and documents the interest in participating in children with ASD. CONCLUSIONS: This study demonstrates the benefits of movement and music interventions and can be considered a useful way to manage autism spectrum disorders in the future.

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17. Kong C, Bing Z, Yang L, Huang Z, Wang W, Grebogi C. Transcriptomic Evidence Reveals the Dysfunctional Mechanism of Synaptic Plasticity Control in ASD. Genes (Basel). 2024; 16(1).

BACKGROUND/OBJECTIVES: A prominent endophenotype in Autism Spectrum Disorder (ASD) is the synaptic plasticity dysfunction, yet the molecular mechanism remains elusive. As a prototype, we investigate the postsynaptic signal transduction network in glutamatergic neurons and integrate single-cell nucleus transcriptomics data from the Prefrontal Cortex (PFC) to unveil the malfunction of translation control. METHODS: We devise an innovative and highly dependable pipeline to transform our acquired signal transduction network into an mRNA Signaling-Regulatory Network (mSiReN) and analyze it at the RNA level. We employ Cell-Specific Network Inference via Integer Value Programming and Causal Reasoning (CS-NIVaCaR) to identify core modules and Cell-Specific Probabilistic Contextualization for mRNA Regulatory Networks (CS-ProComReN) to quantitatively reveal activated sub-pathways involving MAPK1, MKNK1, RPS6KA5, and MTOR across different cell types in ASD. RESULTS: The results indicate that specific pivotal molecules, such as EIF4EBP1 and EIF4E, lacking Differential Expression (DE) characteristics and responsible for protein translation with long-term potentiation (LTP) or long-term depression (LTD), are dysregulated. We further uncover distinct activation patterns causally linked to the EIF4EBP1-EIF4E module in excitatory and inhibitory neurons. CONCLUSIONS: Importantly, our work introduces a methodology for leveraging extensive transcriptomics data to parse the signal transduction network, transforming it into mSiReN, and mapping it back to the protein level. These algorithms can serve as potent tools in systems biology to analyze other omics and regulatory networks. Furthermore, the biomarkers within the activated sub-pathways, revealed by identifying convergent dysregulation, illuminate potential diagnostic and prognostic factors in ASD.

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18. Lee SM, Choi Y, Kim D, Jeong HJ, Do YH, Jung S, Lee B, Choi HJ, Kim S, Oh JM, Jeon S, Han J, Kim Y. Developmental deficits, synapse and dendritic abnormalities in a Clcn4 KO autism mice model: endophenotypic target for ASD. Transl Psychiatry. 2025; 15(1): 28.

Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests. Surprisingly, these symptoms were improved by Risperidone treatment, a drug commonly used to treat ASD. RNA sequencing data from mouse neural progenitor cells (mNPCs) showed that the genes regulating trans-synaptic signaling, transmembrane transport, and neuronal projection development were significantly decreased in Clcn4 knockdown (KD) cells compared to wild type (WT). Moreover, Risperidone treatment increased the genes related to the ion transmembrane transport, membrane potential, and neuron projection development in Clcn4 KD. Abnormalities in synaptic plasticity and dendritic spine formation were also observed in Clcn4 KO compared to WT. We observed that phosphorylation of SYNAPSIN, PSD95, ERK and CREB, as well as the expression of CDK5, were reduced in the brains of Clcn4 KO mice. In Clcn4 KO cortical neurons, the phosphorylation of SYNAPSIN and PSD95 expressions also decreased compared to WT, indicating disrupted synaptic function. Additionally, Sholl analysis revealed a reduction in dendritic branching and neuronal projection length in both mouse and human CLCN4 KD neurons. Finally, the decreased phosphorylation of SYNAPSIN and expression of PSD95 along with dendrite abnormalities were restored after Risperidone treatment. These data suggest that dendritic outgrowth and synapse remodeling may serve as endophenotypic targets for drug efficacy in ASD.

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19. Ma L, Liu C, Song R, Qian Y, Zhang F. Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Integr Neurosci. 2025; 24(1): 24948.

BACKGROUND: Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence. METHODS: The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software. RESULTS: Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = -0.48; 95% CI = -0.66- -0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = -1.15; 95% CI = -2.01- -0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2(')-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03-1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13-0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21-1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521-0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis. CONCLUSIONS: TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.

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20. Medyanik AD, Anisimova PE, Kustova AO, Tarabykin VS, Kondakova EV. Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies. Biomolecules. 2025; 15(1).

Developmental and epileptic encephalopathies (DEEs) are a group of neuropediatric diseases associated with epileptic seizures, severe delay or regression of psychomotor development, and cognitive and behavioral deficits. What sets DEEs apart is their complex interplay of epilepsy and developmental delay, often driven by genetic factors. These two aspects influence one another but can develop independently, creating diagnostic and therapeutic challenges. Intellectual disability is severe and complicates potential treatment. Pathogenic variants are found in 30-50% of patients with DEE. Many genes mutated in DEEs encode ion channels, causing current conduction disruptions known as channelopathies. Although channelopathies indeed make up a significant proportion of DEE cases, many other mechanisms have been identified: impaired neurogenesis, metabolic disorders, disruption of dendrite and axon growth, maintenance and synapse formation abnormalities -synaptopathies. Here, we review recent publications on non-channelopathies in DEE with an emphasis on the mechanisms linking epileptiform activity with intellectual disability. We focus on three major mechanisms of intellectual disability in DEE and describe several recently identified genes involved in the pathogenesis of DEE.

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21. Mirabella F, Randazzo M, Rinaldi A, Pettinato F, Rizzo R, Sturiale L, Barone R. Glycosylation Pathways Targeted by Deregulated miRNAs in Autism Spectrum Disorder. Int J Mol Sci. 2025; 26(2).

Autism Spectrum Disorder (ASD) is a complex condition with a multifactorial aetiology including both genetic and epigenetic factors. MicroRNAs (miRNAs) play a role in ASD and may influence metabolic pathways. Glycosylation (the glycoconjugate synthesis pathway) is a necessary process for the optimal development of the central nervous system (CNS). Congenital Disorders of Glycosylation (CDGs) (CDGs) are linked to over 180 genes and are predominantly associated with neurodevelopmental disorders (NDDs) including ASD. From a literature search, we considered 64 miRNAs consistently deregulated in ASD patients (ASD-miRNAs). Computational tools, including DIANA-miRPath v3.0 and TarBase v8, were employed to investigate the potential involvement of ASD-miRNAs in glycosylation pathways. A regulatory network constructed through miRNet 2.0 revealed the involvement of these miRNAs in targeting genes linked to glycosylation. Protein functions were further validated through the Human Protein Atlas. A total of twenty-five ASD-miRNAs were identified, including nine miRNAs that were differentially expressed in cells or brain tissue in ASD patients and associated with glycosylation pathways, specifically protein N- and O-glycosylation and glycosaminoglycan biosynthesis (heparan sulfate). A number of CDG genes and/or ASD-risk genes, including DOLK, GALNT2, and EXT1, were identified as targets, along with validated interactions involving four key miRNAs (hsa-miR-423-5p, hsa-miR-30c-5p, hsa-miR-195-5p, and hsa-miR-132-5p). B4GALT1, an ASD susceptibility gene, emerged as a central regulatory hub, reinforcing the link between glycosylation and ASD. In sum, the evidence presented here supports the hypothesis that ASD-miRNAs mediate the epigenetic regulation of glycosylation, thus unveiling possible novel patho-mechanisms underlying ASD.

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22. Rezq KA, Albalawi HMH, Alharbi HF. Exploring Social Support and Quality of Life Among Mothers of Children with Autism Spectrum Disorders: A Cross-Sectional Study. Healthcare (Basel). 2025; 13(2).

Background: Mothers of children with autism spectrum disorder (ASD) often experience significant stress, which can adversely affect their quality of life (QoL) and increase their reliance on social support. This study aimed to explore the relationship between social support and QoL among mothers of ASD children and identify associated factors. Methods: A cross-sectional study was conducted from December 2022 to March 2023, involving 218 mothers of ASD children in Saudi Arabia. An online questionnaire was distributed via autism associations. Inclusion criteria were mothers of children under 18 diagnosed with ASD, excluding those with diagnosed mental illnesses. Social support and QoL were measured using the Multidimensional Scale of Perceived Social Support (MSPSS) and the Quality of Life in Autism Questionnaire (QoLA). Statistical analysis was performed using Jamovi software. Results: The mean MSPSS and QoLA scores were 4.87 and 100.88, respectively, with a significant positive correlation (Spearman’s rho = 0.509, p < 0.001). Social support was positively associated with higher education and negatively with having more than one autistic child. QoLA scores were significantly predicted by family income (>SAR 10,000 or US 2667) and MSPSS score (p < 0.001). Conclusions: Social support enhances maternal QoL and is influenced by educational level and income, highlighting the need for targeted interventions to support mothers with multiple ASD children. While individual support is important, prioritizing societal accessibility may offer more effective long-term solutions by proactively addressing systemic challenges faced by autistic individuals and their families.

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23. Ricchiuti G, Tuerlinckx E, Taillieu A, Prinsen J, Steyaert J, Boets B, Alaerts K. Toward effective oxytocin interventions in autism: Overcoming challenges and harnessing opportunities. J Psychopharmacol. 2025: 2698811241309621.

Intranasal administration of oxytocin is emerging as a potential pharmacological option for mitigating social difficulties and regulating stress in autism spectrum disorder. However, initial single-dose and multiple-dose trials showed mixed results, with some demonstrating improvements in social and repetitive behavior and others showing no benefit over placebo. This perspective aims to elucidate factors contributing to this variability and to highlight pitfalls and opportunities in the field. We identified two major factors: design-related elements and individual participant characteristics. Pertaining to design-related elements, optimal dosing regimens have yet to be established, but appear to favor moderate intervention durations (i.e., 4-6 weeks) with intermittent and intermediate dosing (i.e., 24-32 IU every other day). Also, the context of the intervention seems crucial, as enhanced outcomes are mainly observed when oxytocin administration is paired with a socially stimulating and supporting environment. In addition, more adequate outcome measures have to be established to effectively assess oxytocin’s impact, including behavioral scales and objective biophysiological markers tapping into stress and neurophysiological regulation. Future research should also account for individual participant differences in biological sex, developmental stage and cognitive and adaptive functioning, and incorporate (epi)genetic screening to identify responders. Overall, refining study designs and personalizing intervention protocols are essential for optimizing oxytocin’s prosocial and anxiolytic effect in autism.

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24. Wang T, Sharp M, Morella I, Bedogni F, Trajkovski V, Brambilla R, Syed YA. Mice with 16p11.2 Deletion and Duplication Show Alterations in Biological Processes Associated with White Matter. Int J Mol Sci. 2025; 26(2).

Deletion and duplication in the human 16p11.2 chromosomal region are closely linked to neurodevelopmental disorders, specifically autism spectrum disorder. Data from neuroimaging studies suggest white matter microstructure aberrations across these conditions. In 16p11.2 deletion and duplication carriers, potential gene dosage effects may impact white matter organisation, contributing to phenotypes including impaired cognition. However, the biological mechanisms underlying this white matter pathology remain unclear. To bridge this knowledge gap, we utilised mouse models of 16p11.2 deletion and duplication to explore changes in corpus callosum oligodendrocytes, myelination, axon caliber, and astrocytes. Immunofluorescence staining was employed to measure lineage and mature oligodendrocyte numbers, as well as myelin basic protein and glial fibrillary acidic protein fluorescence intensity. Transmission electron microscopy was utilised to evaluate axonal structural alterations related to myelin, such as myelinated axon percentage, diameter, myelin thickness, and g-ratio. Our findings reveal changes in the number of mature oligodendrocytes, myelination levels, axon diameter, and astrocytes in the corpus callosum of mice with 16p11.2 deletion and duplication. Deletion mice displayed a tendency toward reduced counts of mature oligodendrocytes and myelination levels, while duplication mice exhibited a notable increase. Axon diameter variations included a significant increase in axon diameter and myelin thickness in both deletion and duplication mice, but with irregular structure in duplication mice. Variances in astrocytes between genotypes showed significant early increases in development for both deletion and duplication mice compared to wild-type mice, with this rise sustained in duplication mice but significantly diminished in deletion mice at a later stage. Our research reveals changes in the biological mechanisms impacting white matter. Comparison of reciprocal trends in 16p11.2 deletion and duplication mice with wild-type mice suggests the possibility of gene dosage effects. Identification of these mechanisms offers an initial step in unveiling therapeutic targets for associated neurodevelopmental disorder phenotypes.

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25. Yuan Z, Su T, Yang L, Xi L, Wang HJ, Ji Y. Maternal Glycemia and Its Pattern Associated with Offspring Neurobehavioral Development: A Chinese Birth Cohort Study. Nutrients. 2025; 17(2).

BACKGROUND/OBJECTIVES: This study investigates the impact of maternal glycemic levels during early and late pregnancy on offspring neurodevelopment in China. METHODS: Fasting plasma glucose (FPG) and triglyceride (TG) levels were measured in maternal blood during pregnancy, and the TyG index was calculated to assess insulin resistance. Hyperglycemia was defined as FPG > 5.1 mmol/L. Neurodevelopmental outcomes in offspring aged 6-36 months were evaluated using the China Developmental Scale for Children, focusing on developmental delay (DD) and developmental quotient (DQ). Mothers were categorized into four glycemic groups: healthy glycemia group (HGG), early pregnancy hyperglycemia group (EHG), late pregnancy hyperglycemia group (LHG), and full-term hyperglycemia group (FHG). Linear and logistic regression models were applied. RESULTS: Among 1888 mother-child pairs, hyperglycemia and FPG were associated with an increased risk of overall DD (aOR = 1.68; 95% CI 1.07-2.64) and lower DQ (aBeta = -1.53; 95% CI -2.70 to -0.36). Elevated FPG was linked to DD in fine motor and social behaviors. Compared to HGG, LHG and FHG significantly increased the risk of overall DD (aOR = 2.18; 95% CI 1.26-3.77; aOR = 2.64; 95% CI 1.38-5.05), whereas EHG did not. Male offspring were particularly vulnerable to early pregnancy hyperglycemia (aBeta = -2.80; 95% CI -4.36 to -1.34; aOR = 2.05; 95% CI 1.10-3.80). CONCLUSIONS: Maternal glycemic levels during pregnancy influence offspring neurodevelopment, with persistent hyperglycemia significantly increasing DD risk. Early pregnancy hyperglycemia particularly affects male offspring, underscoring the need for glycemic management during pregnancy.

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26. Zampatti S, Farro J, Peconi C, Cascella R, Strafella C, Calvino G, Megalizzi D, Trastulli G, Caltagirone C, Giardina E. AI-Powered Neurogenetics: Supporting Patient’s Evaluation with Chatbot. Genes (Basel). 2024; 16(1).

BACKGROUND/OBJECTIVES: Artificial intelligence and large language models like ChatGPT and Google’s Gemini are promising tools with remarkable potential to assist healthcare professionals. This study explores ChatGPT and Gemini’s potential utility in assisting clinicians during the first evaluation of patients with suspected neurogenetic disorders. METHODS: By analyzing the model’s performance in identifying relevant clinical features, suggesting differential diagnoses, and providing insights into possible genetic testing, this research seeks to determine whether these AI tools could serve as a valuable adjunct in neurogenetic assessments. Ninety questions were posed to ChatGPT (Versions 4o, 4, and 3.5) and Gemini: four questions about clinical diagnosis, seven about genetic inheritance, estimable recurrence risks, and available tests, and four questions about patient management, each for six different neurogenetic rare disorders (Hereditary Spastic Paraplegia type 4 and type 7, Huntington Disease, Fragile X-associated Tremor/Ataxia Syndrome, Becker Muscular Dystrophy, and FacioScapuloHumeral Muscular Dystrophy). RESULTS: According to the results of this study, GPT chatbots demonstrated significantly better performance than Gemini. Nonetheless, all AI chatbots showed notable gaps in diagnostic accuracy and a concerning level of hallucinations. CONCLUSIONS: As expected, these tools can empower clinicians in assessing neurogenetic disorders, yet their effective use demands meticulous collaboration and oversight from both neurologists and geneticists.

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