1. Al-Saleh I, Aljerayed Y, Gheith M, Alobaid N, Alenazi H, Elkhatib R, Aldhalaan H, Alnemer M, Mohamed G, Shoukri M. Longitudinal analysis of maternal exposure to phthalates and bisphenol A and their impact on infant neurodevelopment and autistic behavior: The potential mediating role of thyroid hormones. Int J Hyg Environ Health. 2025; 269: 114647.

This prospective cohort study investigated the impact of maternal exposure to endocrine-disrupting chemicals, specifically phthalates and bisphenol A (BPA), on infant neurodevelopment. From 2019 to 2022, 672 pregnant women consented to participate in the study during their initial prenatal appointments at the Obstetrics and Gynecology Clinic of King Faisal Specialist Hospital & Research Centre. Two urine samples were collected each trimester to measure seven phthalate metabolites and BPA levels. Neurodevelopmental performance was evaluated using the Ages & Stages Questionnaires® Third Edition at 6, 12, and 18 months of age, and the risk of autism was assessed with the Modified Checklist For Autism in Toddlers at 18 months. Linear mixed models and logistic regression were applied to evaluate trimester-specific and overall associations using natural log-transformed urinary concentrations of phthalates and BPA. Our results showed that each one-unit increase in the log-transformed concentration of specific phthalates and BPA was associated with significant changes in infant developmental scores. During the first trimester, elevated levels of mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), and BPA were associated with 4.3 %-5.6 % decreases in gross motor (GM) scores. In contrast, monoethyl phthalate (MEP) and low-molecular-weight (∑LMW) phthalates were linked to 4 %-4.5 % increases in communication (COMM) scores. In the third trimester, MECPP and Σ(3)DEHP were positively associated with GM and fine motor (FM) scores, while MiBP was associated with reduced personal-social (PSoc) scores. Sex-stratified analyses revealed differences in susceptibility, with males showing stronger adverse associations in problem-solving and social domains and females more affected in gross and fine motor scores. Mediation analysis identified free thyroxine (FT4) as a partial mediator, accounting for 12.7 % of the effect of ∑LMW phthalates on COMM scores during the first trimester. However, most mediation effects through maternal thyroid hormones were small and not statistically significant. Additionally, some first-trimester exposures, such as MEP and mono-(2-ethyl-5-oxohexyl) phthalate, appeared to be associated with lower odds of a positive M-CHAT screen. At the same time, MnBP showed a potential increase in risk. However, these exploratory findings were based on crude models and a limited number of positive cases and should be interpreted cautiously. Our study also examined overall exposure to phthalates and BPA across pregnancy, revealing consistent yet subtle impacts across developmental domains. This study adds novel insights by assessing trimester-specific exposures and investigating maternal thyroid hormones as potential mediators of early neurodevelopmental outcomes.

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

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

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3. Cooke K, Ridgway K, Pecora L, Westrupp E, Hedley D, Hooley M, Stokes MA. Outcomes of Experiencing Interpersonal Violence in Autism: A Mixed Methods Systematic Review and Meta-Analysis. Trauma Violence Abuse. 2025: 15248380251357618.

In this review and meta-analysis, we aimed to examine outcomes of interpersonal violence among autistic people. Intersectionality and minority theories suggest that negative outcomes are heightened among people with multiple marginalized identities. Thus, we also aimed to investigate gender-related outcomes of interpersonal violence among autistic people. We conducted a systematic database search with inclusion criteria including mixed methods, peer-reviewed research examining any harmful interpersonal act (e.g., physical, sexual, and psychological) experienced by autistic people. We undertook a random-effects meta-analysis with pooled data from 9 studies, comprising 3,647 autistic participants aged 1 to 80 years. Violence was associated with worsened mental health, with the strongest association for internalizing symptoms (d = 0.66, p < .001; 95% CI [0.51, 0.80]) and suicidal thoughts and behavior (d = 0.63, p < .001; [0.44, 0.82]). Narrative synthesis of 57 studies comprising 37,418 participants (13,127 autistic, 24,291 non-autistic) found violence was associated with numerous adverse health, development, and functional outcomes, including worsened mental health and behavioral difficulties compared to non-autistic controls from childhood. Females and gender minorities reported greater intra- and interpersonal health and development difficulties related to violence, emerging in early childhood and enduring into adulthood. Findings provide strong evidence of lifelong negative outcomes associated with interpersonal violence experienced by autistic people, providing evidence for the relevance of minority stress and intersectionality theories in understanding risk. Indeed, our results raise concerns that autistic people, and particularly non-male (female, gender diverse) individuals, have higher susceptibility for abuse from a young age, while being conditioned to respond with social desirability, superficial adaptivity, and dissociation.

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

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

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5. Michels S, Mali A, Jäntti H, Rezaie M, Malm T. Microglial involvement in autism spectrum disorder: insights from human data and iPSC models. Brain Behav Immun. 2025; 130: 106071.

Autism spectrum disorder (ASD) presents a range of lifelong challenges in social communication, repetitive behaviors, and restricted interests, affecting over 2% of the preschool population. Early neurodevelopmental disruptions, particularly those affecting microglia, appear to be central to the pathophysiology of ASD, with microglia influencing synaptic development and stability in the brain. However, the neurobiological mechanisms underlying ASD are still not fully understood. Traditional ASD studies, which rely on animal models and postmortem tissues, have limitations in capturing human-specific neurodevelopmental dynamics. Recent advances in human model systems, including induced pluripotent stem cell (iPSC)-derived neural cultures and brain organoids, offer promising insights into microglia-neuron interactions relevant to ASD. This review evaluates current research using human-based models to explore ASD pathophysiology, focusing on the role of microglia in neurodevelopment, and discusses the strengths and future potential of these innovative approaches.

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6. Zaleski AL, Craig KJT, Khan R, Waber R, Xin W, Powers M, Ramey U, Verbrugge DJ, Fernandez-Turner D. Real-world evaluation of prevalence, cohort characteristics, and healthcare utilization and expenditures among adults and children with autism spectrum disorder, attention-deficit hyperactivity disorder, or both. BMC Health Serv Res. 2025; 25(1): 1048.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are among the most common neurodevelopmental disorders. However, significant gaps persist in understanding health and healthcare-related needs of individuals diagnosed with ASD and/or ADHD across the lifespan. Thus, this real-world evaluation sought to characterize the prevalence of ASD, ADHD, and co-existing ASD and ADHD (AuDHD); sociodemographics; frequent comorbidities and co-occurring diagnoses; and healthcare utilization and expenditures among members of a large national payor. METHODS: This study represents an observational, cross-sectional evaluation of claims from a large national payor. Retrospective claims analyses of commercial fully insured (C-FI) members from 1/1/2022-12/31/2022 identified diagnoses for ASD and/or ADHD among adults (≥ 18 year) and children (< 18 year). Chi-squared tests, T-tests, and Fisher's exact tests examined between-group differences in sociodemographic, health, and healthcare-related measures among members with neurodevelopmental disorders compared to members without ASD and/or ADHD. RESULTS: Within adults (N = 1,928,106), 4.2% of members (60.2% White, 52.9% female, mean age: 34.1 ± 10.9 year) were diagnosed with neurodevelopmental disorders: ADHD (4.0%, n = 76,515); ASD (0.1%, n = 2,134); or AuDHD (0.1%, n = 1,266) (all P < 0.0001). Within children (N = 464,749), 6.7% of members (47.8% White, 67.5% male, mean age: 11.3 ± 3.8 year) were diagnosed with neurodevelopmental disorders: ADHD (5.0%, n = 23,250); ASD (1.1%, n = 5,098); or AuDHD (0.6%, n = 2,665) (all P < 0.0001). Increased odds (i.e., ≥ 2) for certain co-occurring diagnoses were consistently observed across all three neurodevelopmental cohorts for adults and children, which were primarily behavioral health (BH)-related. Compared to those without neurodevelopmental disorders, both adults and children with ASD and/or ADHD had higher healthcare utilization rates [adults: 615.2 to 1024.8 per thousand per month (PTPM); children: 398.4 to 1205.3 PTPM; all P < 0.001)]; largely owing to increased use of BH-related services, translating to greater total healthcare expenditures [adults: $140.3 to $292.1 per member per month (PMPM); children: $50.8 to $845.4 PMPM; all P < 0.001)]. CONCLUSIONS: Leveraging real-world data of 2,392,855 members from a large national payor, 4.1% of adults and 6.7% of children were diagnosed with ASD and/or ADHD. This population appeared to consistently exhibit specific co-existing diagnoses that frequently co-occur in addition to greater observed healthcare utilization and expenditures. Trial registration Not applicable.

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7. Zhou Q, Li D, Zhang Y, Zhang Q, Li Y, Zhu C, Wang K. Evaluating the effectiveness of intelligent interaction technology in autism interventions: A meta-analysis based on trial assessment. Res Dev Disabil. 2025; 164: 105087.

PURPOSE: This research aims to conduct a systematic review of the literature on the utilization of intelligent interaction technologies, including Extended Reality (XR) and robotic systems, within the context of autism interventions. METHOD: This study commenced on June 16, 2022, and conducted a systematic search of publications from 2017 to 2024 using Boolean terms such as « Virtual Reality » AND « autism » AND « RCT » in PubMed, Web of Science, Cochrane Library, SpringerLink, and Embase. Two reviewers independently conducted research selection, data extraction, and quality assessment (using Cochrane Risk of Bias tool, RoB 2), and resolved differences through discussion. Statistical analysis was conducted in STATA using a random-effects model to calculate Standardized Mean Difference (SMD), supplemented by sensitivity analysis, funnel plot, and Egger’s test to ensure robustness. RESULT: The meta-analysis included 13 studies involving 459 individuals with ASD from different regions (age range: 2-15 years, diagnosed using standardized instruments), including Europe, the Americas, Asia, and the Middle East, but without representatives from Africa. The results showed that intelligent interactive intervention demonstrated significant efficacy (SMD=0.66, 95 % CI: 0.27-1.05, p < 0.001). Subgroup analyses indicated that age and intervention targets influenced the effect size, with particularly pronounced positive impacts observed in preschool-aged children and cognitive interventions. Subgroup analysis of intervention measures showed that the XR group exhibited a more positive effect. In contrast, the robotic group, due to high heterogeneity and wide confidence intervals, did not lead to a conclusion that this intervention was effective overall. Additionally, sensitivity analysis, funnel plots, and Egger's test were conducted, demonstrating that the results are stable and no significant publication bias. CONCLUSION: In conclusion, the overall efficacy of intelligent interaction as an intervention is positive, showing benefits in social, cognitive, and behavioral aspects of ASD, particularly with XR (SMD=0.80, 95 % CI: 0.47-1.13). However, further research is required to ascertain the effects of robots. Furthermore, this study suggests intelligent interaction demonstrated larger effects for preschool-aged children(2-6 years; SMD=1.00, p = 0.007).

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8. Zoga K, Villiere S, Tikiyani V, Edwards-Cintron AF, Thokachichu P, Nicodemus P, Camara PG, Hart MP. Multiple autism genes influence GABA neuron remodeling via distinct developmental trajectories. Genetics. 2025.

Variation in over 100 genes are now associated with increased risk for autism and related neurodevelopmental conditions, but how this variation results in distinct and overlapping behavioral changes is still not well understood. Recent efforts have focused on screening many autism genes at once for functional and phenotypic convergence, and identified subsets that are crucial for many early steps of neurodevelopment. Few studies have screened later steps of neurodevelopment, circuit function, circuit plasticity, or behaviors. We screened twenty conserved autism-associated genes for impact on experience-dependent neuron remodeling in C. elegans. Loss of unc-44/ANK2, set-4/KMT5B, daf-18/PTEN, gap-2/SYNGAP1, and chd-1/CHD8 increased, while unc-36/CACNA2D3 decreased, neurite outgrowth of the GABAergic DVB neuron in adults. Although daf-18/PTEN, set-4/KMT5B, and unc-44/ANK2 had convergent phenotypes, they arise from distinct temporal trajectories with differential impact on DVB pre-synaptic morphology. Screening for the DVB regulated spicule protraction behavior identified multiple autism genes involved, but only unc-44/ANK2 and unc-36/CACNA2D3 were shared between screens. Application of a metric geometry computational framework (CAJAL) to the DVB morphology dataset identified 5 additional genes that impact DVB morphology, including unc-2/CACNA1A and unc-10/RIMS1, which also significantly impacted behavior. This work defines new regulators and molecular mechanisms of experience-dependent neuron remodeling and circuit plasticity, and further links these processes with conserved autism genes. It also demonstrates the utility of using intact, behavior generating circuits in C. elegans, to screen for novel roles for conserved autism genes.

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