1. Boxberger A, Chen B, Olson L, Cordova M, Mahmalji J, Rios A, Linke AC, Fishman I. Correction: Functional connectivity patterns differ as a function of co-occurring attentional problems in preschoolers with autism. J Neurodev Disord. 2025; 17(1): 71.

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2. Chang JC, Chen YC, Lin HT, Chen YL, Gau SS. Identifying gut microbiota composition disparities in autistic individuals and their unaffected siblings: correlations with clinical characteristics. Transl Psychiatry. 2025.

Recent research has begun to illuminate a potential link between autism spectrum disorder (ASD) and the microbial environment. The unaffected sibling design is a valuable approach to identifying markers and protective factors for the condition, particularly in Asian populations lacking specific data. We assessed 239 autistic individuals, 102 unaffected siblings (SIB), and 81 typically developing controls (TDC) aged 4 to 25 years. We analyzed fresh stool samples via 16S rRNA amplicon library preparation and Illumina V3V4 sequencing. We employed taxonomic diversity analysis and microbiota differential abundance analysis to discern variations in microbial composition. In addition, we analyzed the associations between microbiota profiles and autistic symptoms, emotional/behavioral problems, and gastrointestinal symptoms. The SIB had higher alpha diversity, and autistic individuals had a different beta diversity compared to the TDC. Compared to ASD and SIB, the TDC group exhibited a higher relative abundance of microbiota, including Blautia, Eubacterium hallii group, Anaerostipes, Erysipelotrichaceae UCG 003, Parasutterella, and Ruminococcaceae UCG 013 at the genus level. Furthermore, the family Prevotellaceae and genera Agathobacter were predominant in SIB compared to ASD and TDC. We found that the microbial communities were related to autistic symptoms and gastrointestinal symptoms. Moreover, individuals with more Anaerostipes exhibited significantly less social impairment and internalizing problems. Our study reveals unique microbial compositions in the ASD and SIB groups and a relationship between behavior patterns and microbial composition. These findings suggest the potential of microbial interventions for autistic individuals that warrant further exploration.

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3. Filogamo F, Liguori FM, La Rana G, Russo R, Cristiano C. Low-dose combination of ultramicronized palmitoylethanolamide and docosahexaenoic acid on neurosteroid and neuroinflammatory dysregulation in autism spectrum disorders. Neurotherapeutics. 2025: e00816.

Several studies show that neurosteroids currently play a significant role in autism spectrum disorders (ASD). However, the pathway of neurosteroid synthesis involved in ASD remains unclear. This study aimed to investigate the crosstalk between autism and neurosteroids, focusing on the mechanism of allopregnanolone production. We used the BTBR T+ tf/J (BTBR) mouse, a well-established animal model of ASD that exhibits typical autism-like behaviors along with neuroinflammation. In the hippocampus of BTBR mice, we observed a marked overexpression of pregnenolone and a related reduction in allopregnanolone levels. This neurosteroid imbalance also appears to be associated with an inflammatory pattern and the manifestation of repetitive and asocial behaviors. The combination of low doses of ultramicronized palmitoylethanolamide (PEA-um) and docosahexaenoic acid (DHA) restores allopregnanolone production modulating neurosteroidogenesis. In association with neurosteroid modulation, this restoration reduces repetitive behaviors and improves social interactions in BTBR mice, also modulating the inflammatory profile with a significant reduction in proinflammatory cytokines and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. These effects demonstrate an important role of the peroxisome proliferator-activated receptor alpha (PPAR-α), whose expression is particularly reduced in BTBR mice. In addition, the pivotal involvement of PPAR-α was further supported by administering a specific antagonist that abolished the advantageous effects of PEA-um + DHA. Overall, our findings demonstrate the potential synergistic effect of the low-dose combination of PEA-um and DHA, confirming their therapeutic effect in ASD and the involvement of neurosteroids in their mechanism of action.

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4. Lacroix A, Tzang CC, Yu JX, Jacob BK, Alexandrovsky M, Winge-Breen A, Rodak T, Lai MC. Disproportionate mental health risks in autistic females: A rapid review with quantitative and narrative syntheses. Front Neuroendocrinol. 2025: 101229.

Mental health conditions are highly prevalent among autistic people, but an updated synthesis of sex-stratified prevalence data, contributing factors, and support strategies is lacking.To address this knowledge gap, we conducted a rapid review utilizing PRISMA-ScR guidelines. MEDLINE, CINAHL, and PsycINFO databases were searched for studies (2004-2024) including female participants with a clinical autism diagnosis, and with a focus on mental health. Of 8,420 records screened, 218 met inclusion criteria. An exploratory quantitative synthesis of population-based and registry-based studies revealed higher rates of mental health conditions in autistic females than males for anxiety, mood, eating, obsessive-compulsive, psychotic, and personality disorders. Narrative synthesis identified moderating factors, including sex-related physiology, gendered experiences, age, age at autism diagnosis, autism characteristics, and co-occurring conditions. Biological and social mechanisms likely interact as contributing factors. Severe consequences of poor mental health underscore the need for tailored approaches accounting for the specific profiles of autistic females.

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5. Lin L, Zhang Y, Zhou D, Wang Q, Wang X, Sun J, Li H, Cong F. Burden and risk factors of autism spectrum disorder: global study and analysis. Pediatr Res. 2025.

BACKGROUND: Autism spectrum disorder (ASD) is increasingly prevalent globally, making it vital to understand its patterns and contributing factors. METHODS: This study utilized Global Burden of Disease 2021 data to analyze ASD trends from 1990-2021 and project to 2030. Mendelian randomization (MR) was used to investigate links between ASD and brain characteristics, metabolism, blood markers, and gut bacteria. RESULTS: High-income Asia Pacific countries, notably Japan (299.14 per 100,000), exhibit the highest age-standardized disability-adjusted life year (DALY) rates. Our findings also show that as countries advance socially and economically, reported ASD rates tend to be higher (ρ = 0.57). The overall global impact of ASD, measured in DALYs, is predicted to rise by nearly 59% by 2030, largely driven by population growth. The MR analysis suggested connections between ASD risk and specific factors like the size of certain brain areas (e.g., the right parahippocampal gyrus), levels of particular metabolic substances (e.g., methionine sulfone), and the presence of certain gut bacteria (e.g., Bacteroides). CONCLUSIONS: ASD is a growing global health concern with unequal community impact. Identifying potentially modifiable factors related to brain health, metabolism, and gut bacteria offers important clues for developing better strategies for ASD prevention, early diagnosis, and support. IMPACT: Significant disparities in ASD burden exist, with the highest rates in high-income Asia Pacific nations. Global ASD-attributable disability is projected to increase by 2030, posing an urgent public health issue. Mendelian randomization suggests potential causal links between ASD risk and neural, metabolic, and gut microbiota factors. This study provides updated global burden estimates and systematically explores modifiable biological factors for ASD, moving beyond prior observational research. This study emphasizes the need for integrated strategies in ASD prevention, early detection, and intervention to address growing global burden.

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6. Long JS, Ikuta T. Interhemispheric auditory tract microstructure in autism spectrum disorder: A diffusion tensor study. Psychiatry Res Neuroimaging. 2025; 356: 112106.

BACKGROUND: Autism spectrum disorder (ASD) involves social communication differences and may include sensory or auditory-processing differences. The interhemispheric auditory pathway remains understudied. METHODS: Diffusion tensor imaging from ABIDE was analyzed. The interhemispheric auditory tract was reconstructed with probabilistic tractography and diffusion metrics were compared between ASD and matched controls. RESULTS: Probabilistic tractography results from 48 ASD and 38 control participants were analyzed. The ASD group showed lower fractional anisotropy and higher radial diffusivity within the tract than controls, consistent with weaker microstructural coherence and myelin-related differences. LIMITATIONS: Secondary multi-site data without harmonization; no behavioral measures of auditory sensitivity or impulsivity for correlation. CONCLUSIONS: Interhemispheric auditory connectivity differs in ASD and may contribute to speech perception and communication challenges, supporting the tract’s relevance as a potential psychiatry-facing biomarker.

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7. Oakley B, Boatman CA, Baldoza S, Hearn A, Larkworthy C, Kent R, Ozsivadjian A, Doswell S, Dittner A, Roestorf A, Rawal D, Carter B, Simonoff E. Feasibility Study of a Novel App-Based Anxiety Intervention for Autistic People. Autism Res. 2025.

At least 50% of autistic people experience clinically relevant anxiety symptoms. However, reasons for elevated rates of anxiety in autism remain poorly understood and there is a high unmet need for novel and adapted therapies for anxiety that are accessible to autistic people. This study aimed to establish the feasibility of a novel app-based anxiety management tool (« Molehill Mountain ») that has been developed with, and adapted for, autistic people. A single-centre, single-arm feasibility study design was employed, whereby autistic people (≥ 16 years) with mild-to-severe symptoms of anxiety were recruited to a 13-week intervention period (King’s College London, UK; clinicaltrials.gov identifier NCT05302167). Of 123 prospective participants screened, 100 (81%) participants aged 16-74 years (n = 69 female) were enrolled within approximately 15 months. n = 76 (76%) completed an anxiety measure at ~15 weeks (Generalized Anxiety Disorder-7 Item Scale; GAD-7). Most adhered to the full intervention duration: 65% (n = 47), with most using the app weekly (1-6 days per week; 58%). 73% of participants agreed that they found the app easy to use overall and that an app is a good format for offering anxiety support to autistic people. There was a significant reduction in self-reported anxiety symptom severity with mean difference 2.88 (95% CI 1.88, 3.89; p < 0.001; Cohen's d = 0.45). We found that an autism-adapted app-based anxiety management tool is acceptable to the community and associated with reduced anxiety symptom severity in autistic adults, on average. Following optimization to further enhance usability, the efficacy of the Molehill Mountain app for reducing anxiety must now be tested under randomized controlled conditions in a full-scale clinical trial.

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8. Ravichandran I, Kannapiran RT, Ramadass A, Reuben J, Sujeetha B, Srinivas P. Development and Validation of a Home-based Psychosocial Intervention Module for Parents of Children with Autism Spectrum Disorder. Indian J Psychol Med. 2025: 02537176251400234.

BACKGROUND: Despite its high prevalence, autism spectrum disorder (ASD) presents specific difficulties for families, especially in India. Where access to early and affordable treatment is limited. Parents often struggle to manage behavioral and developmental issues due to shortages of trained professionals and high therapy costs. This study aimed to develop and validate a culturally appropriate, low-cost, home-based psychosocial intervention module for parents of children with ASD. This study presents the development and validation of a culturally relevant, home-based psychosocial intervention module for parents of children with ASD in India. Unlike previous research that often focused on clinic-based or resource-intensive interventions, this module integrates evidence-based strategies with parental perspectives and expert input to address real-world challenges in resource-limited settings. Its novelty lies in combining child-focused techniques with parental well-being strategies within a structured eight-session format. By emphasizing accessibility, cultural sensitivity, and feasibility, this work contributes a practical and scalable model that complements existing treatments and bridges critical service gaps. METHODS: The study was conducted in two phases between August 2022 and November 2023. Phase I (development of module): The module was systematically developed through literature review, semi-structured parent interviews, and multidisciplinary expert consultations to identify culturally relevant and feasible intervention components. The preliminary module, consisting of eight structured sessions that integrate behavioral, communication, and emotional regulation strategies derived from Applied Behavior Analysis (ABA) and play therapy principles, was developed based on these inputs. Phase II (validation): The drafted module underwent content and face validation by 15 domain experts using structured rating scales, and item-content validity index (I-CVI) values were computed for each session. RESULTS: The development phase identified key parental challenges, including limited access to therapy, stigma, and financial constraints. In the validation phase, experts rated all module items as highly relevant (I-CVI = 0.86-1.00). Qualitative feedback emphasized the module’s clarity, contextual relevance, and practicality for Indian families. CONCLUSION: The validated intervention module offers a practical, evidence-based framework for ASD interventions in resource-limited settings. A further pilot study will evaluate its acceptability, usability, and impact on parental outcomes and symptom management.

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9. Rieffe C, Hu CQ, Broekhof E. Empathy as risk and protective factor in the development of adolescent aggression; the role of autism unraveled. Sci Rep. 2025.

Empathy can strengthen interpersonal relationships, but the question is to what extent empathy also functions this way in autistic adolescents. Despite previous perceptions of lower empathic levels in autistic adolescents, recent studies have stated otherwise. The present study aimed to investigate the developmental trajectories of affective and cognitive empathy, as well as how they predicted the development of proactive and reactive aggression over time in autistic and non-autistic (allistic) adolescents. Eighty-two autistic (Mage = 11.73 years, SD = 1.34) and 105 allistic adolescents (Mage = 11.49 years, SD = 1.36) between 9 and 15 years old were included in this study. Self-reports were administered at 3 time points with 9-month intervals. Longitudinal analyses revealed both affective and cognitive empathy remained stable over time in both groups. Moreover, higher and increasing levels of affective empathy were longitudinally related to increasing levels of reactive aggression for autistic adolescents only, while no relationship was found for allistic participants. Additionally, higher levels of cognitive empathy were longitudinally related to decreasing levels of proactive aggression in both groups. The outcomes support the assumption that, compared to allistic adolescents, autistic adolescents are more easily over-aroused when affected by another person’s emotional states.

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10. Singh A, Rochester JR, Blain R, Walker VR, Pelch KE, Hannani A, Frye J, Lawler CP, Haugen AC, Garton AE, Rooney AA. Protocol for a systematic evidence map of environmental research related to autism spectrum disorders: the aWARE project. Environ Int. 2025; 207: 109839.

INTRODUCTION: Emerging data supporting the potential contribution of environmental chemical exposures to the etiology of autism spectrum disorders (ASD) led to increased interest, research, and publications. This diverse and rapidly growing body of evidence covers a range of study designs, environmental exposures, and ASD-related outcomes. The amount and complexity of research present barriers to identifying, characterizing, and synthesizing relevant evidence to better understand potential associations. The objective of this protocol is to describe a systematic evidence map (SEM) method for identifying and characterizing published scientific research on early-life environmental chemical and physical exposures and ASD or ASD-related outcomes into an interactive resource called aWARE – a Web-based tool for Autism Research and the Environment. METHODS: A comprehensive search for ASD-related studies will be conducted in PubMed, Web of Science, and Scopus, without limits on publication year or language. Eligibility criteria focused on early-life environmental exposure will guide the selection of relevant articles using DistillerSR® and study characteristics will be extracted using DEXTR, a web-based semi-automated data extraction software. Studies will be categorized based on key concepts including major categories of exposure (e.g., air pollution), evidence stream (human, experimental animal), study design, and ASD outcomes, and visualized as SEMs in aWARE, a queryable and interactive database created using Tableau. Input from the autism community will be used to guide the scope of this project and format of the SEMs to increase the utility of the tool. The results of the SEMs will also be summarized in a brief narrative format. CONCLUSION: This protocol reports pre-specified SEM methods for developing the aWARE tool on ASD and environmental exposures including outreach to the autism community for important input. The resulting project will advance ASD research with the protocol ensuring transparency and replicability.

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11. Yogitha PS, Suchitra MR. Fortified tofu red banana peel as a nutritional modulator: Computational and molecular insights into food-drug interactions and genetic targets in autism spectrum disorder. Comput Biol Chem. 2026; 120(Pt 2): 108739.

BACKGROUND: Neurodevelopmental anomalies are features of drug-induced ASD and often accompany behavioural challenges. A promising approach to mitigating the side effects of antiepileptic treatments involves nutraceuticals and fortified foods. Experimental investigations are laborious, but molecular modelling, including docking and dynamics simulations, elucidates compatibility between drugs and food phytonutrients at the atomic level. AIM: This study aims to formulate and profile the phytonutrients of tofu fortified with red banana peel, predict the computational affinity of TFBP phytonutrients against CNS targets, and evaluate high-affinity bio constituents for drug-food interactions critical in ASD using computational simulations. METHODOLOGY: Fortification of tofu with red banana peel, experimental evaluation of phytonutrients using GC-MS, HPLC, ICP-OES, antioxidant potency, XRD and FTIR. Computational molecular modelling study of food phytonutrient affinity against significant targets of ASD pathological targets using a molecular docking approach. Moreover, a top computational formulation study of drug-food phytonutrient compatibility using explicit molecular dynamics techniques. RESULTS: Nutraceuticals in TFBP showed strong binding affinities with most ASD targets. Tryptophan, benzeneethanamine, and vaccenoylglycerol were key phytochemicals studied for drug-food compatibility. Based on energetics and bulk properties, tryptophan was most compatible with VPA, suggesting its role in modulating neurotransmitter homeostasis, synaptic stability, and autophagy in ASD.

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