1. Angelopoulou M, Siaperas P, Livadas S, Karantana E, Papadimitriou DT, Angelopoulos N. Endocrine circuitry in autism spectrum disorders: A systematic review of mechanistic insights and clinical implications. Neuroscience;2025 (Oct 15);585:351-366.

The increasing global prevalence of Autism Spectrum Disorder (ASD) diagnoses-largely driven by heightened awareness, evolving diagnostic criteria, and improved detection-has intensified efforts to elucidate its complex neurobiological underpinnings, although the true change in occurrence remains uncertain. While much attention has been paid to genetic and neurodevelopmental factors, emerging evidence highlights the crucial role of the endocrine system in modulating social, cognitive, and behavioral outcomes associated with ASD. To systematically review the existing literature on endocrine dysfunction and hormonal signaling pathways implicated in ASD, with the aim of identifying common mechanistic links and evaluating their clinical relevance.A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar for studies published between 1980 and 2024. The review included 183 human studies evaluating associations between ASD and hormonal alterations, encompassing thyroid function, HPA axis dysregulation, growth hormone signaling, sex hormones, obesity, melatonin, oxytocin, vitamin D status, and exposure to endocrine-disrupting chemicals. Alterations in multiple endocrine axes were consistently associated with ASD, including prenatal thyroid imbalances, cortisol rhythm dysregulation, aberrant IGF-1 levels, elevated fetal steroidogenic activity, and impaired oxytocin signaling. Endocrine disruptors such as phthalates and pesticides were also linked to increased ASD risk in susceptible populations. Endocrine dysfunctions are frequently associated with ASD, with multiple hormonal axes potentially influencing its pathophysiology, although causality remains unconfirmed. Understanding hormonal influences across developmental stages could inform early detection strategies and novel therapeutic approaches.

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2. Bearss K, Shih W, Tagavi DM, Kuo Y, Fettig A, Locke J. A Pilot Feasibility Randomized Trial of the RUBI in Educational Settings Intervention With Paraeducators Supporting Autistic Students in Public Elementary Schools. J Autism Dev Disord;2025 (Oct 15)

PURPOSE: This pilot randomized study evaluates the feasibility, acceptability, and preliminary effectiveness of RUBI in Educational Settings (RUBIES), a school-based adaptation of the evidence-based Research Unit in Behavioral Intervention (RUBI) parent training program, when implemented by elementary school paraeducators supporting autistic students with externalizing behaviors that impact safety and well-being. METHODS: A 24-week pilot randomized controlled trial was conducted with 67 paraeducators and 65 autistic students across 39 public schools in the United States. Paraeducators were randomly assigned to RUBIES or an active comparator, Psychoeducation on Autistic Students in Schools (PASS). RESULTS: Feasibility outcomes, including adherence to intervention strategy implementation, were high for paraeducators receiving RUBIES. Acceptability measures demonstrated strong engagement and satisfaction among paraeducators, with RUBIES paraeducators reporting significantly greater confidence in managing student behaviors compared to those who received PASS. While both groups showed reductions in externalizing behaviors, no significant differences were found between RUBIES and PASS on standardized outcome measures of student externalizing behaviors. CONCLUSION: Findings suggest that RUBIES is a feasible and acceptable intervention for paraeducators, though further research is needed to assess its effectiveness in promoting behavioral change in autistic students at school.

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3. Brown CR, Foster JD. Modulation of Autism-Associated Serotonin Transporters by Palmitoylation: Insights into the Molecular Pathogenesis and Targeted Therapies for Autism Spectrum Disorder. ACS Chem Neurosci;2025 (Oct 15);16(20):3964-3977.

Autism spectrum disorder (ASD) is a developmental disorder of the nervous system characterized by a deficiency in interpersonal communication skills, a pathologic tendency for repetitive behaviors, and highly restrictive interests. The spectrum is a gradient-based construct used to categorize the widely varying degrees of ASD phenotypes, and has been linked to a genetic etiology in 25% of cases. Prior studies have revealed that 30% of ASD patients exhibit hyperserotonemia, or severely elevated whole blood serotonin (5HT), implicating the serotonergic system in the pathogenesis of ASD. Likewise, escitalopram, a selective-serotonin reuptake inhibitor (SSRI), has been demonstrated to effectively improve core ASD symptoms potentially by modulating abnormal brain activation in ASD patients. Molecular studies have uncovered proband patients with rare mutations in the serotonin transporter (SERT) that manifest enhanced surface expression and 5HT transport capacity, suggesting that abnormal enhancement of SERT function may be involved in the pathogenesis of ASD. Here, we reveal that palmitoylation is enhanced in the ASD SERT F465L and L550V coding variants, and confirm prior reports of enhanced kinetic activity and surface expression of F465L. Furthermore, treatment of F465L with the irreversible palmitoyl acyl-transferase inhibitor, 2-bromopalmitate (2BP), or escitalopram, rectified enhanced F465L palmitoylation, surface expression, and transport capacity to basal WT levels. Overall, our results implicate disordered SERT palmitoylation in the pathogenic mechanism of ASD, with basal recovery of these processes following escitalopram treatment providing insight into its molecular utility as an ASD therapeutic.

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4. Carpita B, Nardi B, Pini S, Parri F, Perrone P, Pronestì C, Giovannoni F, Russomanno G, Bonelli C, Massimetti G, Cremone IM, Fiorillo A, Dell’Osso L. Social camouflaging of autistic traits is associated with more severe symptoms among subjects with feeding and eating disorders. Eat Weight Disord;2025 (Oct 15);30(1):81.

PURPOSE: Given the high prevalence of autistic traits among individuals with eating disorders (EDs), this study investigates the relationship between social camouflaging and eating disorder symptoms. It specifically examines how camouflaging behaviors may influence the manifestation and severity of disordered eating. METHODS: A total of 70 patients with EDs and 50 healthy controls (HCs) were assessed using the Camouflaging Autistic Traits Questionnaire (CAT-Q) and the Eating Disorder Inventory-2 (EDI-2). Independent samples t tests were used to compare CAT-Q scores between groups. ANOVA followed by Bonferroni post-hoc tests examined differences across EED subtypes. Pearson correlation analyses assessed associations between CAT-Q and EDI-2 scores. Finally, a linear regression model was used to evaluate whether camouflaging (CAT-Q total score) significantly predicted eating disorder symptom severity (EDI-2 total score). RESULTS: ED patients scored significantly higher than HCs across all CAT-Q domains and on the total score (all p < .001). No significant differences in camouflaging scores were observed among the different ED subtypes. CAT-Q domain and total scores were significantly positively correlated with all EDI-2 domains, with few exceptions. Linear regression analysis indicated that CAT-Q total score was a significant predictor of EDI-2 total score (β = .728, p < .001). CONCLUSIONS: Our findings reinforce the notion that social camouflaging, often used as a coping strategy, is associated with the presence and severity of eating disorder symptoms. Overall, the study underscores the complex interplay between autistic traits and disordered eating, highlighting the importance of further research into this connection. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

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5. Chen C, Tsai SY, Tahamata VM, Chuang YH, Cheng Y, Fan YT. Decoding the brain’s excitatory-inhibitory metabolite balance in relation to sensory responsivity and autistic traits. Neuroimage;2025 (Oct 15);320:121470.

Brain excitatory-inhibitory (E-I) balance plays a fundamental role in sensory and social processing. Alterations in E-I neurotransmitter systems-commonly indexed by the glutamate and glutamine (Glx)/GABA ratio-have been implicated in various neurodevelopmental conditions, including autism spectrum disorder (ASD). However, how individual differences in E-I balance relate to sensory responsivity and autism-spectrum-related traits in neurotypical populations remains poorly understood. In this study, we evaluated E-I balance across sensory-related brain regions in 92 neurotypical participants to explore its association with sensory responsivity and autistic traits. Our findings revealed that individuals with higher levels of self-reported autistic traits also exhibited stronger associations with sensory responsivity and higher Glx/GABA ratios. In cross-correlation analyses, the Glx/GABA ratio was significantly associated with both autistic traits and sensory responsivity, whereas Glx alone showed fewer associations. Clustering analyses further grouped autistic traits with the Glx/GABA ratio, rather than with the individual metabolite concentrations, suggesting that the ratio may be more behaviorally relevant than either metabolite alone. Moreover, the prefrontal Glx/GABA ratio demonstrated stronger associations with both autistic traits and sensory responsivity compared to other brain regions, a finding further supported by hierarchical moderation and mediation analyses. Overall, these results suggest that individual variability in regional E-I balance may be meaningfully related to sensory and social-affective traits, even within non-clinical populations. These findings may offer insights into the broader neurobiological mechanisms underlying sensory-affective processing across the general population spectrum.

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6. Chen H, Li M, Yao P, Nie Z, Xu L, Zhang Y, Xu X, Shen C, Huang J, Liu Y, Li Z, Wen J, Zhao L, Cao X. Observed improvements in immune parameters and behavioral symptoms following low-dose IL-2 treatment in four autistic children with immune dysfunction. BMC Psychiatry;2025 (Oct 15);25(1):991.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition for which there are no definitive medications targeting core symptoms. Growing evidence indicates that individuals with ASD exhibit immune dysfunction and evidence of peripheral and central inflammation. Immunotherapy interventions have shown promise in addressing this dysregulation. Notably, low-dose Interleukin-2 (Ld IL-2), an established treatment for certain autoimmune diseases, represents a potential therapeutic approach. Our study aims to investigate the association between Ld IL-2-induced immune modulation and behavioral improvements in children with ASD. This research may offer novel insights into potential treatment strategies for ASD. CASE PRESENTATION: In our previously completed single-arm, self-controlled clinical study (data unpublished), 24 ASD children with immune abnormalities received Ld IL-2 treatment, all of whom showed varying degrees of symptom improvement. This paper presents case reports of four ASD children who demonstrated marked clinical improvement and substantial correction of immune imbalance following treatment. The average age of 4 participants was approximately 6 years old, comprising two boys and two girls. Assessments using the Childhood Autism Rating Scale(CARS), Aberrant Behavior Checklist (ABC), Autism Treatment Evaluation Checklist (ATEC), Krug’s Autism Behavior Scale (CABS), Hospital Anxiety and Depression Scale (HADS), and Caregiver Strain Questionnaire (CGSQ)revealed substantial behavioral improvements and no adverse events. Improvements persisted for three months post-treatment, with notable progress in Speech/Language/Communication and body/health/behavior domains. According to caregivers, there has been a observed improvement in the subjects’ sleep quality, accompanied by a gradual restoration of overall physical health. Immune testing in the four pediatric patients revealed a marked decrease in both the proportion of Type 1 cytotoxic T cells (Tc1) and the Tc1/Regulatory T cell ratio. CONCLUSIONS: Our findings in these four cases describe an association between Ld IL-2 treatment and observed improvements in ASD symptoms, potentially linked to immune modulation.

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7. Chen R, Bai MS, Zhao T, Xue Y, Mohamed ZA, Jia FY. The relationship between screen time and anxiety/depression symptoms in preschool children with autism spectrum disorder: the mediating role of cortical volume. BMC Pediatr;2025 (Oct 14);25(1):818.

BACKGROUND: Both screen time (ST) and the development of cortical volume have significant effects on the mental health of children. This study aims to examine the relationship between ST and mental health in preschool children with autism spectrum disorder (ASD) while investigating the potential mediating role of cortical volume. The findings may provide evidence to support clinical identification and intervention strategies. METHODS: A retrospective observational analysis was conducted on 149 children with ASD aged 18–60 months, who were categorized into two groups based on their daily ST: high-dose exposure (HDE) and low-dose exposure (LDE). The study compared the two groups in terms of demographic characteristics, ASD symptoms, neurodevelopmental level, mental health condition (assessed using the Child Behavior Checklist, CBCL), and cortical volume. Pearson correlation tests were used to determine the direct correlations between ST, cortical volume, and mental health. Multi-step linear regression analysis was used to investigate the mediating effect of cortical volume on the association between ST and mental health conditions. RESULTS: Children in the HDE group showed significantly higher anxiety/depression scores (60.02 ± 28.76 vs. 50.17 ± 23.10, p = 0.03) and reduced cortical volume in the left superior frontal area (25,232.13 ± 3069.41 vs. 26,441.19 ± 3032.22, p = 0.02) compared to the LDE group. ST was positively correlated with anxiety/depression symptoms (r = 0.20, p = 0.02) and negatively correlated with the left superior frontal cortical volume (r= -0.29, p < 0.001). Furthermore, mediation analysis revealed that the cortical volume of the left superior frontal area fully mediated the relationship between ST and anxiety/depression symptoms. CONCLUSIONS: The findings suggest that ST adversely affects the mental health of children with ASD, with cortical volume in the left superior frontal area potentially serving as a key mediator in this relationship. These findings highlight the need for ST management in early ASD interventions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR2100051141. Registered on 14 September 2021. [URL: http://www.chictr.org.cn] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-025-06203-5.

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8. Choi JW, Parenti M, Slupsky CM, Tancredi DJ, Schmidt RJ, Shin HM. Maternal serum and placental metabolomes in association with prenatal exposure to per- and polyfluoroalkyl substances and their relevance to child neurodevelopment in an ASD-enriched cohort. Environ Pollut;2025 (Oct 15);383:126811.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to altered neurodevelopment in children, but the contribution of maternal metabolic disruption to this relationship remains unclear. We investigated associations between prenatal PFAS exposure, maternal metabolism, and child neurodevelopment. We analyzed 172 mother-child pairs from the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Nine PFAS were measured in maternal serum collected during pregnancy. Metabolites were quantified in third-trimester serum and placental tissue using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. At age three, children were clinically classified as having autism spectrum disorder (ASD), typical development (TD), or non-typical development (non-TD), the latter including children with atypical developmental features who do not meet the criteria for ASD. Multiple linear regression assessed associations between individual PFAS and metabolites, and quantile-based g-computation evaluated PFAS mixture effects. Principal component analysis (PCA) summarized metabolomic profiles. One-way analysis of covariance (ANCOVA) and multinomial logistic regression examined associations between metabolites and child neurodevelopment. Correlation network analysis explored relationships among PFAS, serum, and placental metabolites. After multiple comparison correction, perfluorooctane sulfonate (PFOS) was significantly associated with serum 2-hydroxybutyrate (q < 0.10). Higher perfluorooctanoate (PFOA), PFOS, and PFAS mixture levels were associated with lower serum PC-2 scores. Higher serum PC-3 score, reflecting mitochondrial dysfunction, was associated with increased non-TD risk. Network analysis identified 2-hydroxybutyrate as a key serum metabolite potentially linked to PFAS and placental amino acids. Prenatal PFAS exposure was associated with maternal metabolic alterations; however, no clear linkage to child neurodevelopment were observed. These findings suggest the need to consider gene-environment interactions in studies of neurodevelopmental outcomes.

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9. Cleper R, Kapra O, Goldental N, Gross R. The association between autism spectrum disorder and congenital malformations: a population-based nested case-control study. Mol Psychiatry;2025 (Oct 15)

We examined whether specific congenital malformations (CM) detected at birth are associated with increased likelihood of autism spectrum disorder (ASD), by a case-control study nested within a 12-year birth cohort derived from the Israel National Birth Registry. The cohort included all registered ASD cases (n = 2099) and 1:1 age- and sex- matched controls. Overall, CM were more prevalent in the ASD group as compared with controls [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.29-2.38]. This association remained robust after adjusting for birth weight, parental age, parental ethnicity, and maternal immigration [adjusted OR (aOR) 1.61, 95% CI 1.14-2.29]. The most prevalent CM types among the ASD group were circulatory system (2.1 vs. 1.2% among controls) and urogenital organs (1.8 vs. 0.8%). The association between ASD and genital CM was limited to males and persisted in the adjusted models (aOR 2.24, 95% CI 1.16-4.34). In the stratified by sex analysis, a strong association between all non-genitourinary CM and ASD was found in females (aOR 3.47, 95% CI 1.13-10.65). In conclusion, CM, most notably genitourinary in males exclusively, and others (mostly circulatory) in females, are more prevalent in newborns later diagnosed with ASD, as compared with age- and sex-matched controls. These sex-specific CM might represent useful pre- and postnatal markers of ASD, and their presence in newborns at-risk of ASD might indicate earlier and more frequent neurodevelopmental assessments. Our findings might also guide future research of plausible genetic, epigenetic, and prenatal underpinnings of ASD.

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10. Corbera S, Penadés R, Assaf M. Editorial: Underlying neurobiological, genetic, and behavioral mechanisms in schizophrenia and autism spectrum disorder. Front Psychiatry;2025;16:1694809.

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11. Dougnon G, Rummel L, Matsui H. Mutation of ube3a causes developmental abnormalities and autism-like molecular and behavioral alterations in zebrafish. Brain Res Bull;2025 (Oct 15);231:111542.

Mutations in the UBE3A gene are responsible for neurodevelopmental disorders (NDDs), including Angelman syndrome (AS), which is characterized by developmental delays, impaired motor coordination, and cognitive disabilities. In recent years, UBE3A mutations have also been linked to autism spectrum disorders (ASD), due to their significant role in synaptic plasticity and cognitive function. Although substantial research has utilized mammalian models, the zebrafish (Danio rerio) provides unique opportunities to investigate gene functions owing to their transparent embryos, rapid development, and suitability for large-scale genetic and behavioral studies. In this study, we characterized a zebrafish model harboring a point mutation (T > A) in exon 3 of the zebrafish ube3a gene, which induces a stop codon resulting in a truncated protein. We performed comprehensive developmental, behavioral, and molecular analyses to investigate the impact of Ube3a dysfunction at both larval and adult stages. We observed alterations in embryonic development, significant locomotor deficits, including stereotypic movements, and reduced social preference and aggressiveness. Furthermore, RNA sequencing analysis of both larvae and adults revealed dysregulation in chromatin, nucleosome, protein-DNA, and primary cilia-related genes. Our findings provide a functional characterization of the ube3a mutation in zebrafish at both larval and adult stages. This zebrafish model offers new insights into the roles of UBE3A in neurodevelopment and behavior, expanding our understanding of its dysfunction in NDDs.

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12. Hertzog A, Tolun AA, Wykes AD, Brown D, Breit SN, Ellaway C, Ho G, Gold W. Evaluating the utility of growth differentiation factor 15 and fibroblast growth factor 21 as blood biomarkers for Rett syndrome. Sci Rep;2025 (Oct 15);15(1):36017.

Rett syndrome (RTT, OMIM #312750) is a severe genetic, neurodevelopmental disorder, primarily affecting females, that occurs due to pathogenic variants in MECP2. Clinical features include loss of acquired developmental milestones, such as purposeful hand movements and communicative abilities and the onset of stereotypic hand movements. Mitochondrial dysfunction/impairment, and inflammation have been reported in individuals with RTT. Despite numerous clinical trials and medications thought to be disease-modifying, treatment often remains purely symptomatic. A significant impediment in determining treatment efficacy has been the lack of clinical biomarkers that correlate with disease state. Mitokines, such as fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), have been established as biomarkers of cellular stress and mitochondrial dysfunction that may be of clinical utility for patients with RTT. We aimed to determine the suitability of these mitokines as biomarkers for RTT where we analysed their expression levels in blood samples from individuals with RTT as well as fromthe Mecp2(T158A) mouse model . Our data showed higher FGF21 and GDF15 levels in female Mecp2-deficient mice compared to their wild type littermates. Median FGF21 and GDF15 levels also trended higher in the affected human cohort compared to controls; however, these elevations did not reach statistical significance and appear to be correlated with sodium valproate therapy.

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13. Li C, Geng Z, Liu Y, Li X, Wang T, Ahmad M, Luo H, Zhou H, Cui Y. Two-hit immune activation induced autism-like phenotypes in mice: The underlying mechanism may involve the lung-brain axis. Brain Res;2025 (Oct 15);1865:149850.

Neuroinflammation plays important roles in the pathogenesis and development of autism spectrum disorder (ASD). However, the mechanism by which peripheral organ inflammation affects neuroinflammation is still unclear. This study aimed to investigate that the interaction between the lungs and the brain as a potential mechanism underlying this effect. Ovalbumin (OVA) can induce neuroinflammation and cause neurotoxicity, leading to tissue damage or cognitive memory impairment. OVA – induced maternal immune activation (MIA) provides a stable animal model for studying ASD and other human neurodevelopmental disorders. Postnatal reinfection is an additional risk factor for ASD and may lead to pathological and physiological changes. Here we compared the expression of cytokines in the hippocampus and lung tissues of MIA offspring after the second acute immune stimulation at three times post birth, as well as the correlation between cytokines and autism-like phenotypes.Interestingly, our research findings suggest that maternal and postpartum OVA-induced immune activation and lung injury may produce an autistic phenotype, with potential mechanisms involving the lung- brain axis.

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14. Lin G, Xinying G, Jingwen Q, Ziwen S, Xingrong S, Lei P. Deficiency of the innate immune protein IFITM3 impairs phagocytosis and promotes autism-like behaviors in mice. Int Immunopharmacol;2025 (Oct 15);167:115599.

Interferon-induced transmembrane protein 3 (IFITM3) plays a protective role in autism spectrum disorder (ASD), a condition characterized by neuronal degradation and loss. The clearance of apoptotic neurons via efferocytosis activates resolution signaling pathways, driven by phagolysosome-mediated degradation of dying cells. We found that this degradation by phagolysosomal IFITM3 activates the Mer receptor tyrosine kinase/ musculoaponeurotic fibrosarcoma oncogene family B pathway, which drives the proliferation of anti-inflammatory microglia. This efferocytosis-induced microglial proliferation (EIMP) promotes the expansion of resolving microglia. In dexamethasone-induced regression models, IFITM3 depletion inhibits EIMP, reduces apoptotic neuron clearance, and hinders tissue resolution. In conclusion, IFITM3 promotes apoptotic neuron clearance and EIMP in ASD, thereby mediating the resolution of inflammation. These findings suggest that IFITM3 could serve as a potential therapeutic target for modulating neuroinflammation in ASD.

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15. Liu Z, Wu C, Lin Z, Li H, Liu Y, Amjad N, Majid M, Basnet R, Li Z. Triple-phase VPA administration in Sprague-Dawley rats: A cost-effective ASD model unveiling the synaptic-mitochondrial-inflammatory axis as a therapeutic target. Life Sci;2025 (Oct 15);379:123900.

AIMS: To overcome limitations of traditional single-dose valproic acid (VPA) models in autism spectrum disorder (ASD) research-including severe maternal toxicity and imprecise embryonic exposure-this study established a cost-effective ASD model using a three-phase sequential VPA strategy in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Pregnant SD rats received VPA (400 → 450 → 400 mg·kg(-1)) on gestational days 11.5, 12.5, and 13.5. Maternal/neonatal survival, neurodevelopmental milestones, and behavioral phenotypes (open field, three-chamber sociability, repetitive grooming) were assessed. Synaptic ultrastructure (transmission electron microscopy), neuroinflammation (ELISA for IL-1β, IL-6, TNF-α, IL-10), and oxidative stress (CAT, SOD, GSH-Px, MDA) in the prefrontal cortex were analyzed. KEY FINDINGS: The optimized protocol eliminated maternal mortality (p < 0.01) and resorption (p < 0.0001), while enhancing neonatal survival (p < 0.01) and litter size (12-16 pups). Model rats exhibited core ASD phenotypes: social deficits (p < 0.0001), repetitive grooming (P < 0.01), and delayed neurodevelopment. Synaptic vesicle depletion, mitochondrial cristae disruption, proinflammatory cytokine upregulation (p < 0.01), and antioxidant suppression (p < 0.01) confirmed synaptic-mitochondrial-inflammatory axis dysregulation. SD rats outperformed C57BL/6 mice in phenotypic fidelity and modeling efficiency. SIGNIFICANCE: This study pioneers a three-phase VPA strategy that balances high ASD phenotyping fidelity with animal welfare. The synaptic-mitochondrial-inflammatory axis is identified as a novel therapeutic target. SD rats provide a superior, cost-effective platform for ASD mechanism and intervention studies.

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16. Liyew WA, Moges A, Girma F, Abebe W, Afework M. Sensory and cognitive awareness impairment patterns in children with autism spectrum disorder: a factorial analysis of the underlying constructs. Child Adolesc Psychiatry Ment Health;2025 (Oct 15);19(1):112.

BACKGROUND: Individuals with autism spectrum disorder (ASD) have a wide range of challenges related to sensory and cognitive awareness. In Ethiopia, the increasing prevalence of ASD underscores the need for a comprehensive understanding of the associated challenges and impairments, an area that has not been studied so far. OBJECTIVE: The objective of this study was to investigate the underlying patterns of sensory and cognitive awareness impairments in children diagnosed with ASD at autism centers in Addis Ababa, Ethiopia. METHODS: An institution-based cross-sectional study was conducted at the Nehemia Autism Center and the Nia Foundation in Addis Ababa, Ethiopia. The study included children aged 4 to 16 years who had a confirmed diagnosis of ASD. A total of 145 study participants involved in this study. Study subjects were identified in collaboration with staff and caregivers. Caregivers of the study subjects were approached by trained data collectors, and written informed consent was obtained. The sensory/cognitive awareness subscale of the Autism Treatment Evaluation Checklist (ATEC) was administered to caregivers. This questionnaire tool has been validated for the autism population in Ethiopia. A face‒to-face interview was conducted. Data analysis was conducted IBM SPSS Version 22 Statistical Software. Principal component analysis with varimax rotation was employed to examine the patterns of sensory and cognitive awareness impairments. The numbers of principal components and factors to be retained were determined by examining the Eigenvalues and scree plot. Eigenvalues greater than 1 were used. The variable composition of each factor was examined by analyzing the factor loadings in the rotated component matrix. High variable loadings above 0.3 were considered for each factor. RESULTS: This study revealed five patterns of sensory and cognitive awareness impairments in children diagnosed with ASD. Pattern 1, limitation in social engagement and exploration (α = 0.822); Pattern 2 challenges in emotional awareness and cognitive responsiveness (α = 0.743); Pattern 3 challenges in story comprehension and creativity (α = 0.62); Pattern 4 difficulties in social reciprocity and reward (α = 0.34); and Pattern 5 trouble with focus and attention (α = 0.12). All of these patterns accounted for 60% of the total variance. CONCLUSION: In this study, five patterns of sensory and cognitive awareness impairments were identified. Clinicians and therapists may need to consider these patterns for more personalized and effective support of children with ASD.

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17. Macenski C, Ravichandran C, Tran D, McDougle CJ, Thom RP. Psychiatric Clinical Presentations in Adolescents and Adults With Autism Spectrum Disorder With and Without Co-Occurring Gender Diversity: A Retrospective Chart Review. J Autism Dev Disord;2025 (Oct 15)

PURPOSE: Psychiatric presentations and psychopathology in people with co-occurring gender diversity (GD) and autism spectrum disorder (ASD) are not well understood. The aim of this study is to characterize mental health presentations and history (psychiatric diagnoses, psychotropic medication use, history of suicidal ideation and suicide attempts, and psychiatric hospitalization rates) in patients with co-occurring ASD and GD among those seeking psychiatric care at a tertiary care outpatient neurodevelopmental disorders center. METHODS: This retrospective chart review included 125 patients who were divided into three study groups: index patients with co-occurring GD and ASD (n = 25), and age-matched comparison males (n = 50) and females (n = 50) with ASD and without indication of GD in their medical records. All subjects were required to have one initial psychiatric note documented in their electronic medical record (EMR), and their records were reviewed for psychiatric diagnoses, psychotropic medication use, history of suicidal ideation and suicide attempts, and psychiatric hospitalizations. RESULTS: All three groups experienced high rates of psychopathology across all characteristics of presentation and history assessed, aside from psychiatric hospitalization which was infrequent across groups. 119/125 (95%) subjects were assigned two or more psychiatric diagnoses in addition to the ASD diagnosis required for study eligibility. CONCLUSION: Results warrant further investigation of the prevalence of psychiatric conditions in GD individuals with ASD.

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18. Martínez-Minguet D, Noel R, García SA, Costa M, Pastor O. Review of autism spectrum disorder databases for the identification of candidate genes. Database (Oxford);2025 (Jan 18);2025

Research into the genetics of autism spectrum disorder (ASD) seeks to unravel its complex genetic background by identifying genes associated with the condition at varying levels of confidence. While these findings hold significant potential for clinical applications, the dispersed nature of scientific evidence presents a challenge for the reliable identification of ASD candidate genes. Although ASD candidate genes are gathered in genetic databases, these vary widely in the gene sets, biological information, and confidence level classification methods, leading to inconsistencies and complicating research efforts. This study aims to identify and assess the quality and reliability of ASD genetic databases to support more robust identification of ASD candidate genes. Using a Systematic Mapping Study, we identified 13 specialized databases. We then followed a Data Quality Approach in two stages, first assessing Accessibility, Currency, and Relevance dimensions to select the potentially relevant databases to be used as ASD candidate gene sources. The selected databases were analysed, assessing Completeness-at schema and data level-, and Consistency between high-confidence ASD genes. The four selected databases are: AutDB, SFARI Gene, GeisingerDBD, and SysNDD. SFARI Gene demonstrated the highest completeness at schema level (89%), while AutDB showed the highest completeness at data level (90%). However, only 1.5% consistency was observed across the four databases in their classification of high-confidence ASD candidate genes. Our findings highlight the unique contributions of each database and reveal substantial inconsistencies in gene classification, driven by differences in scoring criteria and the scientific evidence considered. These inconsistencies have important implications for both clinical users and researchers, as conclusions may vary depending on the database used. This study supports researchers when using ASD genetic databases, promoting consistent interpretation and improved clinical decisions.

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19. Mathur M, Bess K, Gibson A, Le YC, McKay S. A Cross-Sectional Analysis of the Social Determinants of Health (SDOH) Needs in Early Childhood Among Children at Risk and Diagnosed With Autism Spectrum Disorder. J Autism Dev Disord;2025 (Oct 15)

PURPOSE: Unmet social determinants of health (SDOH) play a significant role in the reported barriers to healthcare access and support experienced by children with autism spectrum disorder (ASD). Limited studies have explored how unmet SDOH needs impact children with ASD during early childhood. This study examined SDOH needs in children with a positive Modified Checklist for Autism in Toddlers (MCHAT) or ASD diagnosis and whether specific needs are more strongly associated with these outcomes. METHODS: Using cross-sectional data from pediatric patients’ electronic health records, descriptive statistics were used to examine the prevalence of SDOH needs and associations were examined using multinomial logistic regression among children (< 5 years of age) with developmental delays. Patients were stratified into 3 groups: (1) no positive MCHAT screen or no ASD diagnosis, (2) positive MCHAT screen and no diagnosis, and (3) ASD diagnosis (ICD-10 code: F84.0). Patients and/or their caregivers were screened for five SDOH factors: food insecurity, housing stability, financial strain, health literacy, and transportation issues. RESULTS: Children diagnosed with ASD had 49% higher odds of reporting at least one SDOH (AOR:1.49, p = 0.045), compared to those with no positive MCHAT screen or diagnosis. Although not significant, a positive MCHAT screen and/or ASD diagnosis trended toward higher odds of financial strain, housing instability, and low health literacy. CONCLUSIONS: The findings emphasize the need to screen and address SDOH, particularly financial risk and health literacy, during early childhood among autistic children. Pediatric primary care SDOH programs should be tailored to better support families' unique needs.

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20. Oliver-Aronson L, Kohn L, Gev T, Golan O. Parental Insightfulness and Its Association With Social Competence in Autistic and Non-Autistic Children. Autism Res;2025 (Oct 15)

Parental insightfulness (PI), the parent’s capacity to reflect upon their own and their child’s mental and emotional states, has been associated with various aspects of children’s socio-emotional development. This study examined PI regarding child-peer interactions and its association with social competence in autistic and non-autistic (NA) children, aged 4-7 years. We hypothesized that parents of autistic and NA children would demonstrate different patterns of PI and that PI would moderate the association between autism diagnosis and social competence. Participants included 68 autistic children and their parents and 46 NA children and their parents. Parents watched videos of their child playing with a peer and completed the Insightfulness Assessment (IA) interview. They also reported on their child’s social competence and their own parental reflective functioning. Results revealed that compared to NA children’s parents, parents of autistic children showed similar levels of positive insightfulness about their child but had greater difficulties maintaining focus on their child’s mental states, showed less acceptance, and more concern about the child. PI moderated the negative association between autism diagnosis and children’s social competence so that in higher PI levels, the association was weaker than in lower PI levels. This study’s findings suggest higher PI may mitigate social challenges for autistic children. Hence, PI and its nuances may be an intervention target for autistic children’s parents with the aim of improving children’s social outcomes.

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21. Schiltz H, Su D, Lerner J, Mazefsky C, Lord C. Development of a Conceptual Model of Loneliness in Verbal Autistic Adults Using Qualitative Content Analyses. J Autism Dev Disord;2025 (Oct 15)

PURPOSE: Loneliness has serious consequences for physical and mental health. Therefore, the high vulnerability of autistic adults to loneliness is concerning (Hymas et al., in: Rev J Autism Dev Disord., 2022. https://doi.org/10.1007/s40489-022-00330-w ). However, foundational questions regarding the operationalization and importance of loneliness to the autistic community remain largely unanswered, and thus were the aims of the current study. METHODS: Procedures followed initial steps of the PROMIS (Patient-Reported Outcomes Measurement Information System) guidelines. A preliminary conceptual model of loneliness was developed based on literature in the general population and presented to focus groups and individual interviews involving 13 autistic adults and 5 autism professionals. Transcripts were analyzed using qualitative content analysis. RESULTS: Participants indicated that research on loneliness in autistic adults was worthwhile because of the commonality, significant negative impact, need to challenge misconceptions, and identify prevention/intervention strategies. Revisions to an initially proposed conceptual model of loneliness in autism included clarifications (e.g., satisfaction with vs. presence of relationships), modifications (e.g., frequency vs. availability of contact), and additions (e.g., social exhaustion, feelings of difference, and animals). CONCLUSION: Our proposed conceptual model of loneliness in autism identifies key nuances and concepts overlooked by models and measures of loneliness developed for non-autistic populations. These findings underscore the need to improve methods for assessing loneliness among autistic adults.

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22. Schwarzlose RF. Infant sensory gating and a developmental cascade to autistic traits and anxiety. Neuropsychopharmacology;2025 (Oct 15)

Disruptions to the infant sensory environment can have lasting effects on neural response properties and behavior in both humans and animals. Recent work has begun to highlight an additional factor in infant sensory experience: differences in inhibitory signaling and sensory gating. Converging work from human and animal studies has begun to implicate a developmental cascade by which impaired sensory gating during a sensitive period of neonatal neurodevelopment promotes a phenotype of sensory over-responsivity, autistic traits, anxiety, and other psychiatric challenges. In this Review, I propose a model for this developmental cascade and highlight how differences in infant sensory responsivity represent an important intermediate phenotype for research, screening, and supportive intervention.

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23. Selçuk Özmen E, Koç AE. Understanding Human Behavior: Examining the Dark Triad of Personality in the Light of Autism Spectrum Traits. Eurasian J Med;2025 (Sep 16);57(3):1-7.

Background: This study aims to examine the relationship between dark triad personality traits and autism spectrum traits, exploring their impact on social skills, communication, imagination, and empathy. By doing so, it seeks to contribute to psychological assessment and intervention strategies in these areas. Methods: The study was conducted with a community sample of adults aged 18 and above. Participants were invited through online platforms to complete an anonymous survey. The survey included a sociodemographic form, the short dark triad scale, and the autism spectrum quotient. Inclusion criteria required participants to be at least 18 years old, have sufficient proficiency in Turkish, and not have any known mental or developmental disabilities that could affect their ability to complete the survey. Exclusion criteria included undergoing psychiatric treatment during the study. Prior to participation, informed consent was obtained from all participants, and voluntary participation was emphasized. Results: The findings revealed a significant negative correlation between autism spectrum traits and Machiavellianism (r=-0.247, P=.001). This suggests that individuals with communication difficulties tend to struggle with manipulative or strategic social behaviors. Regarding the relationship between autism traits and narcissism, results indicated that higher autism-related imagination scores were associated with lower narcissism levels (r=-0.237, P=.002). Individuals with fewer autism traits were observed to have a stronger sense of self-worth. This finding suggests that the construction of an exaggerated self-image, a core component of narcissism, may be negatively influenced by deficits in imagination. On the other hand, no significant relationship was found between psychopathy and autism subdimensions. This indicates that the core features of psychopathy, such as emotional detachment and impulsivity, do not directly align with the structured and repetitive behaviors associated with autism. Conclusion: This study provides important insights into the impact of autism traits and dark triad characteristics on social functioning. Future research should further investigate the cognitive and emotional foundations of these traits using larger and more diverse samples.

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24. Shahraki AG, Houshmand F, Saghaei E, Amini-Khoei H. Cuminaldehyde, a Hopeful Agent, Mitigates Autistic-Like Behaviors, Combating Hippocampal Neuroinflammation in Maternal Separation Stress Model in Male Mice. Dev Neurobiol;2025 (Oct);85(4):e23008.

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that appears in the earliest ages of the lifespan. The causes of ASD remain anonymous, although immunological, genetic, biological, and psychosocial theories have been proposed. Stresses during early life, such as maternal separation (MS), are one of the psychosocial causes of ASD. The neuroimmune response is complicated in the pathophysiology of ASD. Cuminaldehyde (CA) has different pharmacological effects, such as anti-inflammatory properties. This study aimed to explore effects of CA on autistic-like behaviors in maternally separated mice with respect to its probable anti-neuroinflammatory effects. METHODS: Forty male mice were randomly allocated to five groups, including control mice administered with normal saline, and MS groups received normal saline and CA with doses of 5, 25, 50 mg/kg intraperitoneally for 14 continuous days. The three-chamber sociability, the resident-intruder, and shuttle box tests were performed. Subsequently, mice were euthanized, and the expression of the NLRP3, TLR4, HMGB1, and IL-1β genes in the hippocampus was investigated using real-time PCR. RESULTS: MS mice showed diminished sociability preference, damaged passive avoidance memory, as well as aggressive behaviors. Behaviors related to autism in MS mice are associated with a rise in the expression of inflammatory markers in the hippocampus. CA reversed the deleterious effects of MS on behaviors, in addition to a decrease in the expression of inflammatory genes in the hippocampus. CONCLUSION: CA, via attenuation of neuroimmune reaction in the hippocampus, partially mitigated autistic-like behaviors in the MS mouse model.

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25. Shi Z, Jin Y, Xu H, Gao L, Wu M, Chang Y, Song X, Guo X. Altered neurotransmitters in cerebrospinal fluid of children with autism spectrum disorder. Brain Res;2025 (Oct 15);1865:149851.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Neurotransmitter imbalances have been implicated in ASD, but few studies have examined cerebrospinal fluid (CSF) alterations in ASD patients. Identifying specific CSF biomarkers could enhance our understanding of the underlying neurobiology and improve diagnostic and therapeutic approaches. METHODS: CSF samples were collected from 17 children, including 8 with ASD and 9 typically developing controls. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze neurotransmitter levels and metabolites in the CSF samples. Statistical comparisons were performed to identify group differences in neurotransmitter concentrations. RESULTS: ASD participants had significantly lower levels of glutamine, norepinephrine, and kynurenine compared to controls. Neurotransmitter dysregulation, particularly in the glutamine-glutamate cycle, was observed in ASD, potentially contributing to core symptoms. CONCLUSION: Our findings suggest that neurotransmitter imbalances in the CSF could serve as potential biomarkers for ASD. Further research is needed to validate these findings and explore therapeutic interventions targeting these neurotransmitter pathways.

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26. Soltysova M, Tomova A, Paulinyova M, Lakatosova S, Trebaticka J, Ostatnikova D. Gut microbiota in children and adolescents with autism, ADHD and anorexia nervosa, and its link to the levels of satiety hormones. Neuroscience;2025 (Oct 15);585:394-407.

Neurodevelopmental disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and anorexia nervosa (AN) significantly impact affected individuals and their families. This study investigated differences in gut microbiota composition, neurotrophic factors, intestinal inflammation biomarkers, and food intake-regulating hormones between affected children and healthy controls. As these disorders are often accompanied by abnormal eating behaviours, we also explored the levels of food intake regulating hormones and their interrelations with other parameters. Our cohort comprised 117 children, including 65 patients (30 boys with ASD, 21 girls with AN, and 14 patients with ADHD) and 52 age- and sex-matched healthy children. We found several common patterns in dysbiosis of different disorders. Richness was lower in ASD and ADHD, and the Bacteroidetes/Firmicutes ratio was higher in all disorders. The Desulfovibriota abundance was increased in ADHD and AN, and Escherichia-Shigella was elevated in ASD and ADHD. Faecalibacterium abundance was decreased in ADHD and AN. A reduction of Bifidobacterium was also common. Children with ASD exhibited an elevated Bacteroidetes and a diminished Actinobacteriota, and Ruminococcus. Children with ADHD manifested reduced Firmicutes. Girls with AN displayed a decreased Firmicutes and increased Proteobacteria, Cyanobacteria, and Verrucomicrobiota. Calprotectin, zonulin and neurotrophic factors levels showed no significant differences. Lower PYY levels in ADHD and reduced PYY, leptin, and ghrelin levels in AN patients were found. Notably, certain resemblances was observed in the microbiotic taxa abundances across all patient cohorts, underscoring the conceivable influence of gut microbiota composition on the behavioral manifestations of mental disorders.

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27. Voniati L, Georgiou R. Communication and feeding skills in Rett syndrome: Case report. J Intellect Dev Disabil;2025 (Oct 15):1-9.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental condition that causes regression of previously acquired abilities after normal development. RTT symptoms affect communication and feeding skills, which may have serious consequences for individuals with RTT. Essential aspects of their daily care include feeding and language intervention. METHOD: This report describes the case of a 14-year-old diagnosed with RTT. The adolescent engaged in an intervention program focusing on speech, language, and feeding needs. The article provides a comprehensive overview of the evaluation, intervention, and re-evaluation process for the challenges she encountered. RESULTS: Reassessments revealed positive outcomes in the adolescent’s feeding and communication. CONCLUSION: This study underscores the importance of speech and language therapy interventions for individuals with RTT and showcases their effectiveness in improving daily life.

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28. Wu Q, Hong Q, Kim NY, Adolphs R, Paul LK, Charpentier CJ. Variability and stability of autistic traits in the general population: A systematic comparison between online and in-lab samples. Personal Neurosci;2025;8:e5.

The surge of online psychological assessments have brought the autism research community both opportunities and challenges: while they enable rapid large-scale data collection and more power to characterize individual differences, they also bring concerns about data quality, generalizability beyond online samples, and whether autistic traits can be reliably characterized with self-report measures administered online. Here we tackle these concerns by providing a systematic characterization of the autistic traits variability across individuals in a large cross-sectional dataset (N = 2826) as well as its temporal reliability within individuals in a test-retest dataset (N = 247), with both online and in-lab samples. We measured autistic traits using the Social Responsiveness Scale, 2nd version, Adult Self Report (SRS-2-ASR) – a tool that quantifies individual differences in autistic traits along a continuum for the general adult population. Across individuals, we found elevated SRS scores in online samples and were able to trace this effect to specific subsets of SRS items. SRS scores also covaried with internalizing symptoms, decreased with age, and were lower in women compared to other genders. Within individuals, we find moderate-to-good test-retest reliability of SRS scores over long intervals, with no difference between online and in-lab samples, suggesting robust temporal stability. We conclude that there are systematic differences in autistic traits between online and in-lab samples that are partly explained by systematic population-level differences in internalizing symptoms, particularly social anxiety. Future studies that sample across different populations should measure, control for, or stratify with respect to these factors.

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29. Zhang H, Liang Z, Zhuang H, Wang M, Huang Y, Cao X, Chen H, Shen L, Feng C. Proteomic study of plasma and L1CAM-captured exosomal proteins in children with autism spectrum disorders. J Pharm Biomed Anal;2025 (Oct 15);264:116965.

Autism spectrum disorder (ASD) has become a neurodevelopmental disorder that seriously endangers the health of infants and children. In order to explore the pathogenesis of the disease and search for early diagnostic biomarkers. In this study, plasma exosomes (PEs) and neural cell adhesion molecule L1 (L1CAM)-captured exosomes (LCEs) of ASD and controls were extracted and lysed to obtain proteins. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics were applied to investigate the differences in the expression of PEs and LCEs proteins between the two groups. Twenty-eight plasma exosomal differentially expressed proteins (DEPs) were identified, which were mainly associated with immunity, inflammation, complement and coagulation, and lipoprotein metabolism and transport. Twenty L1CAM-captured exosomal DEPs were identified, which were mainly involved in cytoskeleton, tight junctions, focal adhesion, and platelet-associated pathways. Meanwhile, our results suggested that processes or signaling pathways associated with the DEPs from plasma exosomes may be activated, whereas those associated with L1CAM-captured exosome may be inhibited. These processes or signaling pathways have been reported to be associated with ASD in previous studies. These DEPs have the potential to be diagnostic markers. This study provides new insights into disease mechanisms and diagnostic markers of ASD.

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30. Zhang J, Zhang Y, Chen Y, Zhu J. Prenatal stress and cortical morphometric similarity network in offspring: Transcriptional signatures of associated genes. J Affect Disord;2025 (Oct 15);387:119519.

BACKGROUND: Prenatal stress is known to disrupt neurodevelopment in offspring, heightening their risk of mental health disorders. However, its impact on the morphometric similarity network (MSN)-a framework that integrates multiple anatomical features to quantify structural similarity across brain regions in the developing offspring-remains poorly understood. METHODS: Using data from the Queensland Twin Adolescent Brain (QTAB) longitudinal study focusing on adolescent twins, we investigated the impact of prenatal stress on cortical MSN in 414 early adolescents (aged 9-14 years). Furthermore, we analyzed the relationship between MSN strength alterations associated with prenatal stress and anatomically organized gene expressions. Disease-related analysis and functional enrichment analysis were conducted. RESULTS: Adolescents exposed to prenatal stress exhibited smaller age-related changes in MSN strength between ages 9 and 14, particularly in regions associated with emotional regulation, cognitive control, and decision-making, despite showing greater similarity at age 9 compared to their unexposed peers. We identified cortical patterns characterized by weighted gene expression, strongly associated with group differences in MSN strength. Gene expressions linked to prenatal stress-related MSN strength changes were correlated with differential gene expression (DGE) implicated in conditions such as autism spectrum disorder (ASD) and inflammatory bowel disease (IBD). CONCLUSIONS: These results enhance insights into the interplay between gene expression and structural brain changes driven by prenatal stress, highlighting a potential mechanistic link between prenatal stress and neurodevelopmental vulnerability, shedding light on the biological pathways underpinning neurodevelopmental risk factors.

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