1. Babu J, Lal A, Challagundla L, Allen Ot, Griffin M, Gisabella B, Pantazopoulos H. Transcriptomic Profiling of the Amygdala of Children With Autism Spectrum Disorder. Autism Res. 2026: e70333.

A growing number of studies point to a key role of the amygdala in Autism Spectrum Disorders (ASD). The amygdala is involved in several processes in ASD including emotional valence, facial recognition, regulation of social learning, empathy, and anxiety. Brain imaging and postmortem studies demonstrate altered amygdala development in children with ASD, associated with impairment in social behavior and anxiety. There is limited information regarding the molecular pathology of the amygdala in children with ASD. We conducted RNAseq profiling on postmortem amygdala samples from male children (4-14 years old) with ASD (n = 8) and normotypic male children (n = 6). Furthermore, we conducted drug repurposing analysis to identify compounds predicted to reverse the transcriptomic signatures identified in order to identify potential therapeutic targets for development of early intervention treatments. Full transcriptome gene expression profiling implicated molecular pathways involved in neuroimmune signaling, glycogen and carbohydrate metabolism, matrix metalloproteases, neurodevelopment, estrogen receptor signaling, and synaptic signaling. Targeted pathway analysis of the top 10% of genes ranked by log(2) fold change implicated pathways involved in extracellular matrix organization (ECM), immune signaling, and synaptic signaling. Our drug repurposing analysis identified sleep modifying compounds and anti-inflammatory compounds including COX2 and GSK3 inhibitors amongst the top predicted therapeutic compounds. PDGF receptor tyrosine kinase inhibitors were identified as a top potential therapeutic mechanism of action. Collectively, we identified alterations in immune signaling, ECM, and synaptic signaling in the amygdala of children with ASD. Furthermore, our findings highlight a number of potential therapeutic drug targets for development of early intervention strategies.

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2. De Sales-Millan A, Reyes-Ferreira P, González-Cervantes RM, Luna-Álvarez M, Guillén-López S, Cobo-Díaz JF, Ramos S, Aguirre-Garrido JF, Velázquez-Aragón JA. Clinical Improvement and Taxonomic-Functional Gut Microbiome Remodeling After Six Months of Multi-Strain Synbiotic Supplementation in Mexican Children with Autism Spectrum Disorder. Nutrients. 2026; 18(15).

Background/Objectives: Gut dysbiosis in children with autism spectrum disorder (ASD) has been associated with alterations in microbial ecology and metabolic function that may contribute to gastrointestinal dysfunction and the severity of clinical manifestations. Synbiotic and probiotic supplementation has emerged as a promising microbiome-targeted strategy for ASD; however, its effects on gut microbiome composition, functional potential, and clinical outcomes remain incompletely understood. We conducted a longitudinal study of Mexican children diagnosed with ASD to analyze changes in the composition, diversity, and functional potential of the gut microbiome during six months of multi-strain synbiotic supplementation. Methods: Stool samples were collected from 25 children with ASD at baseline and after 3 and 6 months of multi-strain synbiotic supplementation. Gut microbiome composition and diversity were analyzed by 16S rRNA gene sequencing, whereas whole metagenome sequencing (WMS) was performed in a subset of samples to evaluate the functional potential of the fecal microbiome. Gastrointestinal symptoms were assessed using the Rome IV criteria, and ASD severity was evaluated with the Childhood Autism Rating Scale (CARS). Results: Twenty-five children with ASD completed the 6 months of synbiotic supplementation. Overall, ASD severity decreased, reflected by a reduction in total CARS score, and improvements in several CARS domains. Gastrointestinal symptoms also decreased significantly. Longitudinal microbiome profiling revealed significant taxonomic and diversity changes over the supplementation period, while WMS identified changes in microbial metabolic potential, including enrichment of tryptophan biosynthesis pathways and reduced L-rhamnose degradation. Conclusions: This exploratory research provides proof-of-concept evidence supporting multi-strain synbiotic supplementation in children with ASD. Larger controlled studies are needed to confirm these findings and clarify their relevance to microbiota-gut-brain axis interactions. The observed concordance between clinical improvements and microbiome remodeling supports further investigation of microbiome-targeted interventions according to ASD severity and duration of supplementation.

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3. Ganachaud B, Mendoza-León MJ, Marchix J, Tello AF, Scoul CLB, Opazo MC, Neunlist M, Riedel CA, Caillaud M, Boudin H. Interaction of the Gut Microbiota and the Enteric Nervous System: Implications in Gastrointestinal Disorders Associated With Autism Spectrum Disorder. Autism Res. 2026; 19(8): e70328.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, restricted interests, and repetitive behaviors. In addition to these core behavioral symptoms, gastrointestinal (GI) disorders are frequently reported, ranging from severe constipation to diarrhea. The links between ASD and gut dysfunction are further supported by alterations in gut microbiota composition and in bacteria-derived metabolites. As the intrinsic nervous system of the digestive tract, the enteric nervous system (ENS) plays a central role in gut physiology by exerting neuronal control on several gut functions, including motility. Located at the interface between the gut microbiota and intestinal function, the ENS may play a key role in the GI symptoms associated with ASD, as demonstrated in several mouse models. This review aims to summarize the interconnected alterations of the gut microbiota and the ENS in ASD, with a particular focus on the microbiota-derived mediators that are altered in ASD, among patients and animal models, and that may affect ENS development and function. By highlighting these interactions, this review seeks to provide new insights on the digestive pathophysiology of ASD, which may also contribute to the severity of behavioral symptoms.

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4. Jiao J, Zhang H, Yang X, Tan L, Li T, Tang X. Night-to-Night Changes in REM Sleep Are Associated With Symptom Severity in Children With Autism Spectrum Disorder: A Two-Night Home Polysomnography Study. Autism Res. 2026: e70322.

Sleep disturbances are highly prevalent in autism spectrum disorder (ASD), yet conventional single-night polysomnography (PSG) provides limited insight into dynamic sleep regulatory processes. Using the Synaptic Homeostasis Hypothesis as a conceptual framework, we quantified night-to-night changes (Δ; Night 2 - Night 1) in sleep architecture across two consecutive nights of home-based PSG and examined their association with ASD symptom severity. Seventy-nine children with ASD, stratified into mild ASD (M-ASD, n = 35) and moderate-to-severe ASD (MS-ASD, n = 44) subgroups using the Childhood Autism Rating Scale, and 30 typically developing controls (TDC) participated. Overall sleep-continuity changes were broadly comparable between ASD and TDC groups. However, sleep-architecture Δ measures showed a severity-related pattern: the M-ASD subgroup exhibited an overnight increase in rapid eye movement sleep percentage (ΔREM% = +2.6%, p = 0.002), whereas the MS-ASD subgroup showed no significant change (ΔREM% = -0.1%, p = 0.922). An adjusted pairwise comparison indicated a greater ΔREM% increase in M-ASD than in MS-ASD (adjusted mean difference = 3.4%, 95% CI: 1.2 to 5.6; Bonferroni-corrected p = 0.009). A similar exploratory difference was observed for NREM1%. ΔREM% was modestly and negatively associated with ASD symptom severity in correlation analysis (ρ = -0.234, p = 0.038) and age- and gender-adjusted regression analysis (β = -0.286, p = 0.016). Sensitivity analyses showed broadly consistent patterns, although severity-stratified overall effects were attenuated after FDR correction. These findings support further investigation of PSG-derived dynamic sleep measures as hypothesis-generating correlates of clinical heterogeneity in ASD. This study examined how sleep changed from one night to the next in children with autism. Children with milder and more severe autism showed different patterns of REM sleep change, and smaller night‐to‐night REM sleep change was modestly associated with more severe autism symptoms. These findings suggest that examining sleep dynamically across nights may provide useful information, but further studies are needed before these measures can be used in clinical assessment. eng.

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5. Jung AW, Supptitz J, Hummes PN, Rodrigues RJK, Nunes ML. The relationship between congenital infections and autism spectrum disorder: a systematic review. J Pediatr (Rio J). 2026; 102(5): 101591.

OBJECTIVE: The aim of this systematic review (SR) is to evaluate the relationship between congenital infections (Toxoplasmosis, Cytomegalovirus, Rubella, Herpes simplex type 1 and 2, HIV, Zika, and Syphilis) and the development of Autism Spectrum Disorder (ASD). DATA SOURCE: The authors seek to identify loopholes in the current knowledge about this content and to understand the role of congenital infections in children’s neurodevelopment. After the systematic search, 32 articles were included. Quality of articles was evaluated by the e Newcastle-Ottawa Scale (NOS). FINDINGS: The data obtained were heterogeneous; the NOS varied from 4 to 9. In 19 studies, an association between congenital infection and the development of ASD and/or features of this spectrum was not observed. Furthermore, the present findings indicate that the link between congenital infections and ASD varies depending on the pathogen and there is no common causal factor among the diseases, as their mechanisms are not yet fully understood. CONCLUSION: This review highlights that there is a possible correlation between some congenital infections and the development of ASD, as is the case with CMV, Zika, Rubella and Toxoplasmosis infection. As the mechanisms are not yet fully understood, there is a need for further studies and research on this topic to bridge the existing knowledge gap regarding its mechanisms.

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6. Russell K, Arcebido K, Ibarra AM, Barella S, Evans A, Shinkre S, Soda T. Reasons for refusal of genetic testing in the evaluation of autism spectrum disorder and intellectual developmental disorder with longitudinal follow-up on test completion. Genet Med Open. 2026; 4: 104413.

PURPOSE: Autism and Intellectual and Developmental Disorder (IDD) are neurodevelopmental conditions influenced by genetic factors. Health organizations recommend genetic testing as part of medical care for individuals diagnosed with autism and IDD. Genetic etiologies can improve counseling accuracy and refine patient treatment, but despite the benefits, studies show that patients often decline clinically offered testing. METHODS: We analyzed data from 7539 health records of autistic individuals with IDD and identified 111 instances with documented refusal of genetic testing (GT). Then, we rechecked the charts with previously documented refusal 4 years later for subsequent acceptance. RESULTS: Reasons for refusal were « access issues » (46.8%) predominantly related to « insurance/cost, » « personal concerns » (21.6%) regarding « procedure » or « no interest, » and « deferred » (19.8%); some refusals were « not specified » (13.5%). Of those individuals who initially declined genetic testing, 29 (26.1%) obtained testing upon follow-up review; the initial reason for refusal was not predictive of later completion of tests. CONCLUSION: These findings indicate a need to address external barriers, such as cost and insurance. Reducing discomfort and increasing accessibility to information regarding autism/IDD GT benefits, importance, and alternative DNA collection methods could also increase awareness, interest, and access to testing. Longitudinal results indicate that providers should follow up on GT for all autism/IDD patients who decline it.

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7. Simple O, Estlin EJ, Okello KK, Okello MO, Akello F, Okello J, Odong F, Ssebyala E, Idro R, Abbo C, Vincent J. Prevalence, Distribution, Co-occurring Neurodevelopmental Conditions, and Associated Factors of Autism Among Children in Northern Uganda. Autism. 2026: 13623613261468802.

Autism is a neurodevelopmental condition characterized by differences in social interaction, communication and behaviour. Despite a global prevalence of one in 127 individuals, autism remains underdiagnosed in low-resource settings. We examined the epidemiology of autism among children aged 2 to 9 years in Northern Uganda. Using multistage sampling, 1,139 children were screened for neurodevelopmental conditions using the validated 23Q screening tool. Children who screened positive underwent clinical assessment, and suspected cases received specialist assessments according to DSM-5-TR criteria. Descriptive statistics and Firth logistic regression were employed for analysis. The mean age was 5.38 years (SD = 2.07), and 51.0% were male. The prevalence of autism was 10.5 per 1,000 children (95% confidence interval [CI] [6.0, 18.5]), of whom 75.0% had co-occurring neurodevelopmental conditions. Autistic children were more likely to have intellectual disability, epilepsy, learning disabilities, global developmental delay, attention-deficit/hyperactivity disorder, dyslexia, cerebral palsy, hearing impairment and speech delay (p < .0045). After adjusting for gender, family history of autism (adjusted odds ratio [aOR] = 6.95, 95% CI [1.60, 30.23]), teenage motherhood (aOR = 8.30, 95% CI [1.30, 53.12]), breech presentation (aOR = 12.23, 95% CI [1.83, 81.64]), and oxygen resuscitation at birth (aOR = 4.56, 95% CI [1.08, 19.33]) were independent predictors of autism. These findings highlight the need to strengthen early identification and targeted services for autistic children in low-resource settings.Lay AbstractAutism affects how people communicate, interact, and process information, and about one in 127 people worldwide are autistic. In low-resource settings, autism is often under-researched and underdiagnosed. We carried out a study in Northern Uganda to estimate how common autism is among children aged 2 to 9 years, to identify co-occurring neurodevelopmental conditions, and to explore factors that may increase likelihood of autism. We enrolled 1,139 children from diverse communities using a multi-step sampling process. After parental consent, one child per household was screened with the 23Q neurodevelopmental screener. Children with possible conditions received further assessment by trained health care workers, and likely cases were confirmed by specialist clinicians using DSM-5-TR diagnostic criteria. Approximately 1 in 95 children were autistic, and none had previously received a diagnosis of autism. The average age of the children diagnosed with autism was about 5 years, and slightly more than half were boys, and most lived in rural areas. Most autistic children (82%) had at least one additional neurodevelopmental condition, such as intellectual disability, learning delays, or epilepsy. Autism was linked to family history, teenage motherhood, and certain birth complications. Improving maternal care, community awareness, and early diagnosis could better support autistic children in Northern Uganda.

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8. Tadenev ALD, Pratt SL, Lopez G, Mexicotte A, Wray A, Burgess RW. Assessing vision and autism spectrum disorder-relevant social interaction phenotypes in Dscam mice. Behav Brain Res. 2026; 510: 116271.

Down syndrome cell adhesion molecule (DSCAM) is an immunoglobulin-superfamily cell-adhesion molecule important for neuronal survival, morphogenesis, synaptic specificity, and particularly retinal organization. Pathogenic variants in Dscam have been linked to developmental disorders including Autism Spectrum Disorder (ASD), Down Syndrome (DS), developmental delays and intellectual disabilities. Here we work to better understand the link between morphology and function in the nervous system by assessing the effects of Dscam mutations on both visual and ASD-relevant social interaction behaviors. While it is known that Dscam deficiency leads to perturbations in retinal organization, the subsequent effect on vision is not well studied. We found that homozygous conditional deletion of Dscam in the retina impacted optokinetic response and visual acuity; however, mice were still capable of image discrimination. In addition, Dscam heterozygous mice were used to test ASD-relevant social interaction and other phenotypes, matching the monoallelic human genetics of DSCAM variants in association studies. The Dscam heterozygous mice performed normally in the open field test, rotarod assay, forced swim test, and both the three chamber and dyadic social interaction assays. Overall, we found that our Dscam deficient mice provide a good model for exploring the relationship between retinal anatomy and visual behavior. However, heterozygous mice did not provide a good behavioral model for ASD. To fully understand the role of Dscam in neurodevelopment, additional functional and physiological studies will be necessary.

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