1. Alves JAB, Lopes M, Gomes Junior SC, Costa RP, Amaral YD, Brandão PG, Brasil P, Raja AI, Brickley E, Nielsen-Saines K, Moreira MEL. Neurodevelopment of children exposed and unexposed to Zika virus in pregnancy: a cross-sectional analysis. Cien Saude Colet. 2026; 31(8): e07652026.

This article aims to assess the neurodevelopment of children with and without in utero Zika virus (ZIKV) exposure, in the absence of microcephaly at birth, and to explore social and biological factors associated with develop- mental outcomes. Cross-sectional analysis of 172 children (94 ZIKV-exposed, 78 unexposed), aged 11-39 months, were evaluated using the Bayley Scales of Infant and Toddler Development. . Outcomes were classified as delayed (<70) or at risk (70-84) across cognitive, language, and motor domains. Exposure was confirmed by maternal RT-P- CR or neonatal IgM. Overall, 30.8% of children presented with developmental delay or risk in at least one domain. The most affected domain was language (26.7%). There were no statistically significant differences in delay frequency cognitive and motor domains.

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2. Aydemir U, Yarımkaya E. Effects of Parent-Child Coparticipation in Physical Activity on Physical Activity Levels and Motor Skills of Children With Autism Spectrum Disorder. Adapt Phys Activ Q. 2026: 1-10.

This study aimed to examine the effects of parent-child coparticipation in physical activity (PA) on the PA levels and fundamental motor skills (FMSs) of children with autism spectrum disorder. Participants were assigned to one of the following three groups: (a) a parent-child group (n = 14), (b) a child group (n = 13), and (c) a control group (n = 13). After 8 weeks of intervention, the within-group comparison revealed a significant increase in PA levels and FMSs in children with autism spectrum disorder in the parent-child group and the child group (p < .001). The between-group comparison further showed that children in the parent-child group had statistically higher scores for PA levels and FMSs than children in the child and control groups (p < .001). These findings suggest that parent-child coparticipation in PA may be a promising component of family-based interventions to promote PA and facilitate the acquisition of FMSs among children with autism spectrum disorder.

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3. Blackburn AD, Esterer M, Justice N, Modi A. Implementing RUBI Group Parent Training for Children With Developmental Disabilities: Real-World Feasibility and Clinical Outcomes. Am J Intellect Dev Disabil. 2026: 1-14.

This study evaluates the feasibility, acceptability, and preliminary outcomes of the Research Units in Behavioral Intervention (RUBI) Parent Training program in an adapted group format within a community-based clinical setting. Caregivers of children aged 3 to 12 years with autism spectrum disorder or other developmental disabilities (DD) participated in 10- or 12-week RUBI groups. Data from 141 participants were retrospectively analyzed using electronic health records and standardized caregiver-reported measures. Results indicated moderate attendance (71.8% session attendance), with disparities observed by insurance type and race. Significant improvements were found in child emotional dysregulation and caregiver stress, while noncompliant behaviors showed no significant change. Outcomes were consistent for youth with autism and youth with other DD. Caregiver satisfaction was high, with 94% reporting perceived behavioral improvement and 100% recommending the program. This is the first known study to evaluate RUBI in a heterogeneous developmental population beyond autism. Findings support the feasibility and effectiveness of RUBI in a group format for diverse developmental populations, although attendance differences and cultural responsiveness warrant further investigation.

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4. Chu X, Su YE, Zhou M, Hou W. Categorical induction in children with autism spectrum disorder: Exploring potential sources of individual differences. J Exp Child Psychol. 2026; 273: 106639.

Categorical induction, the cognitive process by which the specific properties of category exemplars are extended to novel instances, is not absent in children with autism spectrum disorder (ASD); however, it appears to be partially impaired. The basis of these children’s difficulties with categorical induction is not well understood. The current study examined categorical induction ability and the potential sources of individual differences from the perspectives of both linguistic and cognitive abilities. Twenty-two children with ASD and 36 age- and nonverbal IQ-matched typically developing (TD) children were tested for categorical induction, receptive vocabulary, semantic judgement, and executive function (inhibitory control, working memory, and cognitive flexibility). Both groups demonstrated some understanding of category structure by extending properties to above-chance levels. However, relative to controls, children with ASD showed significantly lower consistency and overall performance. Unlike TD children’s categorical induction ability, which was significantly associated with all measured linguistic and cognitive skills except inhibitory control, the ability of children with ASD was significantly related to semantic judgement, inhibitory control, and executive function. Hierarchical regression analyses revealed that executive function was positively associated with categorical induction performance in the ASD group. These findings extend previous research by highlighting the associations of category-based inductive reasoning with linguistic and cognitive abilities in preschool-aged children. The present results hold significant implications for understanding individual differences in inductive reasoning in children with ASD, including potential similarities or differences between children with ASD and other populations.

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5. Demily C, Soumier A. Microbiota-dependent enterocyte oxytocin signaling in autism: mechanisms and translational implications. Mol Psychiatry. 2026.

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6. Fazioli L, Hadad BS, Denison RN, Yashar A. Perceptual meta-uncertainty reveals enhanced calibration of sensory confidence in autism. Sci Adv. 2026; 12(34): eaee2332.

Atypical metacognition has been suggested to underlie autistic phenotypes, given its role in social cognition and behavioral flexibility. However, no study has quantitatively assessed metacognitive abilities in autism. Here, we measured meta-uncertainty-the noise corrupting estimates of one’s own decision uncertainty-in autism. In three experiments, autistic and non-autistic participants (N = 145) performed orientation categorization tasks while simultaneously reporting their choice confidence. By independently manipulating each Bayesian component-sensory uncertainty, prior, and reward-and fitting a recently established process model, we assessed metacognitive abilities and their contingency on the Bayesian components while controlling for first-order decisions. Unlike non-autistic participants, autistic participants’ meta-uncertainty depended on which decision component was manipulated and was lower than that of non-autistic participants, specifically when decisions were adjusted for sensory uncertainty. These findings reveal that metacognition in autism is not generally reduced but rather enhanced for inferences that rely primarily on sensory information.

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7. Frayman D, Mandy W. Rising autism identification in England, 2016-2024: evidence from England’s School Census. J Child Psychol Psychiatry. 2026.

BACKGROUND: Since the 1990s, rates of autism spectrum disorder (henceforth ‘autism’) diagnosis have increased dramatically. To understand if this growth is ongoing, and to understand the changing profile and needs of those with an autism diagnosis, we investigated time trends (2016-2024) in: (a) the number and proportion of UK school pupils identified as autistic; and (b) the characteristics of these autistic pupils, in terms of their age, sex, ethnicity, socio-economic position and co-occurring needs. METHODS: The study used annual data from the School Census (2016-2024) in England, covering 8-8.5 million pupils in each census year. Autism was identified as a pupil having a recorded autism-specific special educational need or disability (SEND). RESULTS: The prevalence of identified autism grew rapidly, from 1.5% in 2016 to 3.3% in 2024. During this time, the male-to-female ratio of autistic pupils fell from 4.9-to-1 to 2.8-to-1, and the proportion of autistic pupils with an identified intellectual disability fell from 15.1% to 8.7%. Across the study timeframe, autistic pupils were more likely to be White British and from an economically deprived background. We found evidence of ‘locked in’ future increases in prevalence from the movement of cohorts up the school system. CONCLUSIONS: As indexed by SEND data, rates of autism diagnosis in England continue to grow, in part driven by greater recognition of girls and those without intellectual disability. These findings highlight the need for forward planning to meet the growth and evolving profile of people with autism-related needs, in education and beyond.

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8. Groenman AP, Welling LE, Pieters S. The monthly spectrum: Premenstrual symptoms across ADHD and autism. Womens Health (Lond). 2026; 22: 17455057261476912.

BackgroundWomen with ADHD and autism experience elevated rates of premenstrual problems, yet no direct comparisons between these conditions exist in adults.ObjectivesThis study examined premenstrual dysphoric disorder (PMDD) prevalence, symptoms, and impairment across ADHD, autism, and neurotypical women.DesignCross-sectional data from 199 women aged 20-40 without hormonal contraceptive use were analyzed across two samples.MethodsParticipants included 89 with ADHD, 39 with autism, and 71 controls. Premenstrual symptoms were assessed using the Premenstrual Symptoms Screening Tool (PSST), alongside measures of ADHD characteristics, autism traits, and sensory hypersensitivity.ResultsBoth ADHD and autistic women showed significantly elevated provisional PMDD rates according to the PSST screening instrument compared to controls, with no significant difference between neurodivergent groups. Dimensional analyses revealed positive associations between premenstrual symptoms and neurodiverse traits, particularly inattention, hyperactivity-impulsivity, and social skills difficulties. The impact of premenstrual problems was similarly associated with these traits across diagnostic groups. Contrary to hypotheses, sensory hypersensitivity was not independently associated with premenstrual symptoms after controlling for ADHD and autism characteristics.ConclusionsPremenstrual problems constitute a significant burden for both ADHD and autistic women, with dimensional associations suggesting that individuals with more severe neurodivergent traits face heightened risk. Yet our findings also demonstrate that prevalence estimates are only as reliable as the recruitment strategies behind them. Advancing this field requires both greater clinical attention to menstrual cycle-related difficulties in neurodivergent populations and recruitment strategies that yield dependable estimates. Many individuals with ADHD or autistic individuals report premenstrual problems such as low mood, irritability, or headaches in the days before their period. Until now, no study had directly compared these individuals with ADHD or autism to each other, so it was unclear whether one group was more affected than the other. We studied 199 individuals with a menstrual cycle aged 20 to 40 who were not using hormonal contraception: 89 with ADHD, 39 with autism, and 71 individuals without either diagnosis. Everyone completed a short questionnaire about premenstrual symptoms, along with measures of ADHD characteristics and autism traits. A subsample also completed a measure on sensory sensitivity. Individuals with ADHD and autistic individuals were both more likely than those without these classifications to screen positive for premenstrual dysphoric disorder (PMDD), a severe form of premenstrual difficulty. The two neurodivergent groups did not differ from each other. We also found that the more neurodivergent traits a person reported, especially inattention, hyperactivity and impulsivity, and social difficulties, the more premenstrual symptoms she tended to report, and the more those symptoms affected her daily life. This pattern held regardless of classification. Sensory sensitivity was not related to premenstrual problems. Overall, premenstrual problems appear to be a real and meaningful burden for both ADHD and autistic women, and individuals who reported more traits seem to be at greater risk. However, our results carry a note of caution: Our results show a strong indication of selection bias, where those individuals recruited for a study on premenstrual problems showed a much higher prevalence than those recruited for a study on sleep. Progress in this field will require both more clinical attention to menstrual cycle difficulties in neurodivergent women and recruitment methods that produce trustworthy estimates. eng.

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9. Heyworth M, Tan DW, Pellicano E. The Impact of « Harmful Behaviours » on Parents of Autistic Children. Autism. 2026: 13623613261476379.

In existing literature, an Autistic child’s « externalising behaviour » (e.g., aggression, defiance) is often associated with poor parental mental health outcomes. Yet few studies have considered the extent and nature of the impact of a child’s harmful behaviours (physical harm to self, others, and property) on parents qualitatively. Here, we examined how Autistic and non-autistic parents conceptualise their Autistic children’s harmful behaviours, and the impact of such behaviours on parents. We analysed 39 Autistic and non-autistic parent interviews using reflexive thematic analysis, from which we identified four themes. Theme 1 encompassed parents’ experiences of their children’s harmful behaviours. Theme 2 captured parents’ explanations for their children’s harmful behaviours, which they understood as indicating intense distress. In Theme 3, parents reflected on their responses to periods of crisis, during which they prioritised safety but acknowledged a systemic lack of support hindered their efforts. Finally, Theme 4 describes the detrimental impacts on parent mental health, including feelings of helplessness, grief, guilt, and fear for the future. We show that it is imperative to more openly discuss child harmful behaviours in neuroaffirming ways, to develop responsive and appropriate parental and familial supports, which acknowledge the role of guilt and trauma in parental mental health.Lay AbstractLots of research suggests that an Autistic child’s so-called « externalising behaviour » (like aggression or defiance) has a negative impact on that child’s parents’ mental health. But, so far, very few studies have talked directly to parents about why and how they experience distress because of their child’s externalising behaviours. In this study, we interviewed 39 Autistic and non-Autistic parents of Autistic children, to better understand their experiences of specific externalising behaviours. For this study, we were particularly interested in children’s « harmful behaviours, » which we defined as violence towards self, others, and/or property. We wanted parents to tell us in their own words what their experiences of such harmful behaviours were, how they understood these periods of crisis, what they did to respond to their children’s harmful behaviours, and what they felt about the behaviours. When we analysed parents’ responses, we came up with four main ideas or « themes. » Parents saw harmful behaviours as a combination of child self-harm, suicidal behaviour, and physical violence to their parents, siblings, and property (Theme 1). But parents did not necessarily blame their child, instead understanding that their child’s behaviour was likely an indication of intense or extreme distress or dysregulation (Theme 2). Parents wanted to keep their whole family safe, but they found they had limited options to do this, and they felt there was little or no support to help them during crises (Theme 3). Unfortunately, parents expressed lots of different emotions, like helplessness, grief, guilt, and fear, as a result of their child’s harmful behaviours (Theme 4). We need to understand better what is happening in families, how they are responding, and what support they need to cope so that we can help families who are experiencing these kinds of crises. This article addresses these questions.

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10. Hu X, Zeng Y, Li J, Lin Q, Liang Z, Zhang J, Jiang M, Gao S, Liu H. Research on the role of gut microbiota metabolites in autism by multi-omics and network pharmacology. Front Microbiol. 2026; 17: 1811435.

OBJECTIVE: The relationship and underlying mechanisms linking the gut microbiota, metabolites and autism spectrum disorder (ASD) have not been fully elucidated. METHODS: In the present study, network pharmacology was combined with machine learning for a systematic investigation into the possible action mechanisms between metabolites derived from the gut microbiota and their targets in ASD. Subsequently, untargeted metabolomics analysis and 16S rRNA sequencing were utilized for investigating alterations in differential metabolites and the composition of principal gut microbiota between normal and BTBR mice. RESULTS: The findings demonstrated that five characteristic targets: CXCR3, HCAR2, HTR1A, IL-6 and NFKB1 modulated by the gut microbiota and gut microbiota’s metabolites were significantly associated with ASD. The M-S-M-T network prioritized 21 candidate gut-microbiota-derived metabolites, including phenylacetic acid and coumarin. These candidates were generated from database-based target prediction and should be interpreted separately from the differential metabolites detected in fecal metabolomics. Metabolomic and 16S rRNA sequencing analyses revealed that BTBR mice displayed metabolic dysregulation and disrupted gut microbiota composition compared with normal ones. These findings suggest that phenylalanine metabolism and neuroactive ligand-receptor interaction may be associated with ASD-like behavioral phenotypes in BTBR mice and warrant further experimental validation. The gut microbiota-metabolite-behavior network analysis further uncovered significant associations among the behavioral characteristics of ASD, alterations in gut microbiota composition and markedly altered metabolite profiles. CONCLUSION: By integrating network pharmacology, transcriptomic re-analysis, fecal metabolomics and 16S rRNA sequencing, this study identifies candidate microbe-metabolite-target associations related to ASD-like phenotypes. These results provide testable hypotheses for future mechanistic studies of gut-brain communication in ASD.

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11. K AS, Beckerson ME, Yeh FC, Kana RK. Quantitative Anisotropy of the White Matter Microstructure Underlying Language Tracts in Autism. Brain Connect. 2026: 21580014261479964.

BACKGROUND AND AIM: Autism is a neurodevelopmental condition that involves differences in social communication and restricted behaviors, often accompanied by altered structural and functional brain connectivity. This preliminary study examined differences in structural connectivity of language-related white matter tracts between autistic and neurotypical (NT) children, exploring the impact of such differences on language comprehension. METHOD: Diffusion-weighted imaging data were acquired from 25 children (13 autistic and 12 NT) on a Siemens 3T MAGNETOM Prisma MRI scanner. Data were processed using DSIstudio. Using deterministic tractography, we mapped 16 white matter fiber tracts and assessed diffusion metrics. Correlational tractography examined whole-brain white matter differences, controlling for age, gender, and full-scale IQ. Reading comprehension was assessed using the Gray Oral Reading Test-Fifth Edition, and regression analyses were conducted to examine associations with quantitative anisotropy (QA). RESULTS AND CONCLUSIONS: Autistic children showed significantly higher QA in 6 of the 16 language-related tracts and higher isotropic diffusion in 2 tracts, suggesting denser fiber bundles with more surrounding free water. In the autistic group, lower QA, particularly in the left arcuate fasciculus, was associated with better reading comprehension, whereas, in NT children, higher QA was associated with better reading. These findings suggest that autistic children may rely on different, more localized white matter pathways for reading compared with the more integrated language networks observed in NT children. Divergent QA-reading comprehension relationships across groups suggest that QA may serve as a candidate biomarker for stratifying language-based interventions.Statement of Importance:This study demonstrates that autistic children exhibit higher Quantitative Anisotropy (QA) in language-related white matter tracts and elevated isotropic diffusion, indicating dense fiber bundles with increased extracellular fluid. Importantly, while higher QA in the left arcuate fasciculus associated with better reading comprehension in neurotypical children, lower QA was associated with better comprehension in autistic children. These findings suggest that autistic individuals have distinct, localized neural pathways for reading rather than integrated canonical networks. QA serves as a promising biomarker to guide individualized language interventions and track neurostructural plasticity.

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12. Raspanti A, Pizzo R, Gurgone A, Giraudo C, Sagona G, Macioce A, Battaglia A, Katsanou L, Comai D, Medici G, Ferrini F, Pizzorusso T, Ciani E, Giustetto M. Postnatal sensory experience and barrel cortex alterations anticipate autistic traits in a mouse model of CDKL5 deficiency disorder. Prog Neurobiol. 2026; 264: 102949.

Autistic traits may arise from atypical sensory experience during postnatal life, but whether there is a causal link between defects in cortical circuitry in the brain, altered sensory processing and social behavior remains unknown. Here, we studied tactile stimuli processing in the barrel cortex (BC) and social interactions in juvenile male mice lacking Cyclin-dependent kinase-like 5 (CDKL5), a model of a severe neurodevelopmental disease showing autistic traits and sensory impairments. We identified in these mice defects of whisker-dependent postnatal sensorimotor reflexes, NMDA receptors-dependent signaling, and dendritic orientation in thalamic inputs-receiving spiny stellate neurons. We also found that CDKL5 is required for mapping and processing whisker-derived tactile stimuli in the BC. Intriguingly, KO mice show autistic traits at P21 that are ameliorated by neonatal CDKL5 replacement in the BC. Our data suggest that CDKL5 is required to link tactile processing in the BC to the onset of social interaction abilities.

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13. S P, R E. NeuroMimicNet: A Multimodal Neuromorphic Framework for Early Screening and Cognitive Pattern Recognition in Children with Autism. J Multidiscip Healthc. 2026; 19: 605039.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition which is composed of social, behavioral, and communication challenges that generally require early detection. PURPOSE: This research proposes NeuroMimicNet, a brain-like event-driven neuromorphic computing framework designed for early screening and cognitive pattern recognition in children with autism. The framework integrates audio signal and facial expression images as multimodal inputs to capture both neural and behavioral patterns. METHODS: The audio modality involves pre-processing steps including noise elimination and normalization, while the neuromorphic processing of audio features is done with Spike-Timing-Dependent Plasticity (STDP), Hebbian learning and a Loihi-inspired spiking neural processing model to capture temporal auditory patterns efficiently. The facial expression images are pre-processed through face alignment, resizing and normalization, and high-level visual features are extracted using a pretrained ResNet50 convolutional neural network. The extracted audio and image features are fused at the feature level to form a unified multimodal representation. The fused features are then classified into four ASD severity level such as Typical, Mild, Moderate, and Severe using a supervised classification model. RESULTS: Performance is evaluated using accuracy, F1-score, precision, recall, and computational efficiency across benchmark EEG-autism datasets. Experimental results demonstrate that NeuroMimicNet achieves higher accuracy and faster response compared to conventional deep learning models. CONCLUSION: NeuroMimicNet highlights the potential of biologically inspired neuromorphic computing for pediatric ASD screening. By combining multimodal behavioral and neural cues with event-driven processing, the framework offers improved interpretability, scalability and clinical relevance.

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14. Shadid OH, Hains PG, Han VX, Yan J, Griffiths M, Pang I, Bandodkar S, Robinson PJ, Dale RC. Shared dysregulation of complement and phosphorylation pathways in the cerebrospinal fluid of encephalitis, Aicardi-Goutières syndrome, and autism. Dev Med Child Neurol. 2026.

AIM: To identify shared and disorder-specific molecular alterations across encephalitis, Aicardi-Goutières syndrome (AGS), and autism spectrum disorder (ASD) using cerebrospinal fluid (CSF) proteomics. METHOD: In this cross-sectional case-control study, mass-spectrometry-based proteomics was performed on archived CSF samples collected between 2016 and 2019 from children with encephalitis (n = 15, nine males, mean age 8 years 2 months, SD 3 years 8 months, range 2-13 years), genetically confirmed AGS (n = 7, five males, mean age 5 years 4 months, SD 4 years 5 months, range 1 year 10 months-14 years), and ASD (n = 10, 10 males, mean age 7 years 2 months, SD 4 years 4 months, range 2-15 years). Each cohort was compared with age-matched and sex-matched non-inflammatory neurological disorder controls. Differentially abundant proteins (false discovery rate [FDR] < 0.05) and enriched pathways were identified using Reactome. Selected proteins were validated using targeted mass spectrometry (selected reaction monitoring or high-resolution multiple reaction monitoring). RESULTS: Encephalitis showed increased immunoglobulin and acute-phase proteins, with reduced glycolysis, synaptic, and extracellular matrix proteins. AGS demonstrated increased interferon signalling, Toll-like receptor pathways, and synaptic proteins, with reduced neural structural and extracellular matrix proteins. ASD exhibited increased extracellular matrix organization and oxidative protection proteins, with decreased haemostatic and stress response proteins. Complement and innate immune pathways were enriched across all cohorts, with increased abundance of C1S, C1R, CFH, and C4A. INTERPRETATION: This hypothesis-generating study shows shared complement activation across encephalitis, AGS, and ASD, which suggests complement dysregulation as a common neuroimmune mechanism and potential biomarker in childhood neuroinflammation.

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15. Tavares GA, O’Reilly L, Frederick NM, Shapiro DA, Vicchiarelli A, Sullivan M, Jiang N, Mattes M, Goelz C, Uchegbu N, Brown H, Lubera J, Wolfe L, Boylan BT, Bergmann C, DeSilva TM, Louveau A. Macrophage-mediated refinement of the dural lymphatic regulates social behavior. Neuron. 2026; 114(16): 3024-42.e5.

The meningeal lymphatic vasculature has recently emerged as a central player in the regulation of brain function under normal and pathological conditions. The dorsal meningeal/dural lymphatics expand uniquely postnatally during a critical window for brain maturation. The mechanisms driving their development and function, however, remain poorly understood. Here, we demonstrate that the developing dorsal meningeal lymphatic vasculature, contrary to peripheral counterparts, undergoes defined refinement orchestrated by cell death and phagocytosis by meningeal macrophages. Alteration of this refinement is observed in the BTBR mouse model of autism spectrum disorder (ASD) and appears to regulate ASD-like social behavior. Together, our results demonstrate a new pathway regulating meningeal lymphatic development that may contribute to brain maturation and function.

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16. Vasconcelos IKM, da Silva Pitombeira MH, Fontenele DR, Vasconcelos Q, Aragão GF. Behavioral pharmacology of isolated cannabidiol in animal models of autism spectrum disorder: a systematic review. Psychopharmacology (Berl). 2026.

RATIONALE: Autism spectrum disorder (ASD) is characterized by differences and challenges in social communication and interaction, restricted and repetitive behaviors, and variable cognitive alterations. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with a complex pharmacological profile, has been investigated in preclinical models of ASD, particularly regarding its behavioral and neurobiological effects. OBJECTIVES: To systematically evaluate the behavioral effects of isolated cannabidiol in animal models of ASD and examine associated neurobiological correlates relevant to central nervous system function. METHODS: A systematic search was conducted in eight electronic databases without date restriction. Preclinical studies assessing isolated CBD in animal models of ASD were included. Owing to methodological heterogeneity, data were synthesized according to the Synthesis Without Meta-analysis (SWiM) guideline, with behavioral outcomes defined as primary endpoints and neurobiological measures as secondary outcomes. The review protocol was registered in PROSPERO (CRD420251003869). RESULTS: Nine studies met the inclusion criteria, predominantly using rodent models, especially valproic acid-induced ASD, as well as zebrafish larvae and one behavioral ASD-like rat model. CBD produced dose-, model-, and treatment-regimen-dependent improvements in repetitive behavior, social interaction, recognition memory, and locomotor hyperactivity. Anxiolytic-like effects were inconsistently reported. Behavioral modulation was accompanied by changes in neurobiological markers, including CB1 receptor expression, parvalbumin-positive interneuron density, oxidative/nitrosative stress parameters, and qualitative neuroanatomical and cellular alterations in brain regions implicated in ASD-related behaviors. However, sex-specific effects could not be adequately assessed because most rodent studies used only males, zebrafish studies were conducted at larval stages, and mixed-sex data were not stratified. CONCLUSIONS: Evidence from animal models suggests that isolated CBD exerts promising but heterogeneous behavioral effects in ASD-relevant paradigms, supported by neurobiological changes that may help explain some behavioral outcomes. However, substantial methodological variability, limited sex-specific analyses, and incomplete reporting of bias-control procedures limit certainty, highlighting the need for more rigorous preclinical studies addressing dose-response relationships, mechanisms, sex as a biological variable, safety, long-term outcomes, and translational relevance.

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17. Wang H, Zhang Y, Jiang Y, Ren J, Hu J, Wang F, Yang L, Sun C, Wu L, Zou M. Integrated network pharmacology and lipidomics provide insights into potential mechanisms underlying the effects of cannabidiol in a rat model of autism. Psychiatry Res. 2026; 365: 117405.

BACKGROUND: Cannabidiol (CBD) has shown potential benefits in managing symptoms associated with autism spectrum disorder (ASD), although its underlying mechanisms of action remain unclear. This study investigated whether CBD improves ASD-like behavior in association with changes in lipid metabolic disturbances and apoptosis-related signaling in a prenatal valproic acid (VPA) rat model. METHODS: Male offspring from VPA-exposed rats received CBD (10 mg/kg, intraperitoneal, twice daily) for 7 days starting on postnatal day 21. Behavioral testing evaluated hyperactivity, social interaction, and repetitive behaviors. Hippocampal lipid profiles were quantified by UPLC-MS/MS. Candidate mechanisms were examined through a joint pathway analysis integrating lipidomics with curated target information, followed by targeted gene/protein validation (qPCR, Western blotting) and molecular docking. RESULTS: CBD treatment improved VPA-induced hyperactivity and repetitive behaviors and social interaction deficits. Lipidomics demonstrated remodeling of hippocampal lipid abnormalities after CBD treatment, with changes across major classes, including phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Joint pathway analysis pinpointed potential targets-LDHA, LDHB, PKM, PTGS2, and EPHX2-linked to energy-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, propanoate metabolism) and arachidonic acid metabolism. CBD also modulated apoptosis-related protein dysregulation, with potential involvement of Akt-related signaling. Docking results suggested possible binding between CBD and the selected targets. CONCLUSION: These results suggest that CBD improves ASD-like behaviors alongside hippocampal lipid metabolism remodeling and modulation of apoptosis-related signaling in VPA-exposed rats, providing preliminary insights into potential mechanisms underlying the effects of CBD in ASD models.

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