1. Andrade C. Autism Spectrum Disorder, 1: Genetic and Environmental Risk Factors. J Clin Psychiatry;2025 (Apr 14);86(2)

The global prevalence of autism spectrum disorder (ASD) has quadrupled during the past 3 decades; the reasons for this are many and include broadening of the diagnostic concept, increased awareness of the disorder, increased screening (including of adults and of girl children), and, possibly, increased exposure to environmental risk factors. This article examines genetic and especially environmental risk factors for ASD. Unsurprisingly, hundreds of potential genes have been identified, many of which overlap between ASD, schizophrenia, depression, and cardiometabolic disorders. Likewise, over a hundred environmental exposures have been associated with ASD risk. These include exposure to parental and family characteristics, exposure to maternal disorders arising during pregnancy, exposure to chronic maternal disorders present during pregnancy, exposure to fetal and other pregnancy-related problems/events, exposure to neonatal problems/events, exposure to maternal nutritional deficiencies during pregnancy, maternal exposure to substances during pregnancy, maternal exposure to pharmacological agents during pregnancy, in utero exposure to toxic substances, and early life exposure to toxic substances. Some of the risk factors identified may be causal, some may be markers of intermediary mechanisms, and some may be unrelated markers. About 40 of these risk factors have been confirmed in meta-analysis for association with ASD. Nearly 70 maternal diagnoses have also been associated with ASD, but, after correcting for false discovery error and shared risk, only 30 remain; and, of these 30, almost all may be explained by genetic and environmental risk factors shared between mother and child, judging from findings in discordant sibling pair and paternal negative control analyses. Caveats and nuances in the interpretation of risks are briefly discussed.

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2. Arsenault J, Kong T, Saghian R, Weng OY, Pathak SS, Yang C, Chao OY, Rakhaminov G, Forman-Kay JD, Ditlev JA, Yang YM, Wang LY. Essential lipids enrich membrane-associated condensates to rescue synaptic morpho-functional deficits in a mouse model of autism. Cell Rep;2025 (Apr 14);44(5):115573.

Synaptic proteins form intracellular condensates with their scaffolds, but it is unknown whether and how essential lipids transform dynamic cytosolic condensates into stable, functional macromolecular assemblies at the membrane. We show that docosahexaenoic acid (DHA), independent of canonical fatty acid receptor 4 signaling, facilitates the re-localization of cytosolic « full-droplet » condensates composed of the key synaptic elements PSD95 and Kv1.2 to the plasma membrane as « half-droplets. » To exploit the therapeutic potential of DHA in vivo, we briefly place juvenile wild-type and Fmr1 KO mice, modeling human fragile X syndrome (FXS), under DHA-enriched or -depleted diets. DHA reverses the inhibitory overtone by promoting the re-localization of presynaptic PSD95-Kv1.2 condensates to interneuron terminal membranes and corrects morpho-functional synaptic defects and stereotypic behaviors. These findings reveal an unexpected role of essential lipids in translocating dynamic condensates into stable synaptic condensates, providing long-lasting benefits for rectifying excitation-inhibition imbalance in FXS and potentially other neurodevelopmental disorders.

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3. Aziz-Zadeh L, Ringold SM, Jayashankar A, Kilroy E, Butera C, Jacobs JP, Tanartkit S, Mahurkar-Joshi S, Bhatt RR, Dapretto M, Labus JS, Mayer EA. Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology. Nat Commun;2025 (Apr 14);16(1):3465.

While it has been suggested that alterations in the composition of gut microbial metabolites may play a causative role in the pathophysiology of autism spectrum disorder (ASD), it is not known how gut microbial metabolites are associated with ASD-specific brain alterations. In this cross-sectional, case-control observational study, (i) fecal metabolomics, (ii) task-based functional magnetic resonance imaging (fMRI), and (iii) behavioral assessments were obtained from 43 ASD and 41 neurotypical (NT) children, aged 8-17. The fMRI tasks used socio-emotional and sensory paradigms that commonly reveal strong evoked brain differences in ASD participants. Our results show that fecal levels of specific tryptophan-related metabolites, including kynurenate, were significantly lower in ASD compared to NT, and were associated with: 1) alterations in insular and cingulate cortical activity previously implicated in ASD; and 2) ASD severity and symptoms (e.g., ADOS scores, disgust propensity, and sensory sensitivities). Moreover, activity in the mid-insula and mid-cingulate significantly mediated relationships between the microbial tryptophan metabolites (indolelactate and tryptophan betaine) and ASD severity and disgust sensitivity. Thus, we identify associations between gut microbial tryptophan metabolites, ASD symptoms, and brain activity in humans, particularly in brain regions associated with interoceptive processing.

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4. Bonemazzi I, Ancora C, Ferasin V, Lunghi M, Toldo I. Towards the phenotyping of autism spectrum disorder in children with tuberous sclerosis complex. Dev Med Child Neurol;2025 (Apr 14)

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5. Chełchowska M, Gajewska J, Szczepanik E, Mazur J, Cychol A, Kuźniar-Pałka A, Ambroszkiewicz J. Oxidative Stress Indicated by Nuclear Transcription Factor Nrf2 and Glutathione Status in the Blood of Young Children with Autism Spectrum Disorder: Pilot Study. Antioxidants (Basel);2025 (Mar 6);14(3)

This pilot study investigated the relationship between nuclear transcription factor Nrf2 and glutathione homeostasis in children with autism spectrum disorder (ASD), addressing the role of oxidative stress in ASD pathophysiology. Oxidative stress, characterized by an imbalance between reactive oxygen species and antioxidant defenses, has been implicated in ASD and may contribute to neuroinflammation and mitochondrial dysfunction. Nrf2, a key regulator of the antioxidant response, influences glutathione synthesis and recycling, making it critical for cellular redox balance. This study included 23 children with ASD and 21 neurotypical healthy controls, and measured levels of Nrf2, Keap1 (Kelch-like ECH-associated protein 1), reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), and peroxidase (GPx3) in blood samples. Our study reveals altered antioxidant defense in children with autism spectrum disorder, as evidenced by reduced levels of Nrf2, Keap1, GSH, and GR, along with elevated GSSG and a lower GSH/GSSG ratio. These findings indicate an increased oxidative stress burden in this population. Additionally, the observed positive correlation between Nrf2, GSH, and GR levels suggests an important role for Nrf2 in maintaining glutathione homeostasis. Our results underscore the potential involvement of oxidative stress in ASD and emphasize the need for further research into targeted therapeutic approaches to address this imbalance.

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6. Church BA, Rodgers JD, Jackson BN, Wisniewski MG, Moppert S, Lopata C, Thomeer ML, Mercado E, 3rd. Perceptual discrimination learning in children with and without autism: The effect of feedback, modality, and progressive-learning. Psychon Bull Rev;2025 (Apr 14)

Research suggests autistic children learn and generalize visual family-resemblance categories atypically (e.g., Church, et al., 2010, 2015), particularly when learning incidentally from exposure. This may reflect differences in perceptual learning (Mercado et al., 2020). However, it is unknown whether perceptual discrimination learning is also atypical and if differences extend to other modalities. To address this, autistic children with normal language abilities and IQ and typically developing (TD) matched comparison children completed auditory and visual discrimination tasks, after either incidental exposure to or direct training with stimuli presented in either progressive (easy-to-hard) or random orders of difficulty. In the visual task, both autistic and TD children only performed well after progressive training, suggesting limited perceptual learning from incidental visual exposure. In the auditory task, autistic children showed a progressive learning advantage after both exposure and training, but TD children only showed this advantage after training. They also had significantly better auditory discrimination than TD children after progressive training. These findings suggest typical visual discrimination learning after progressive training and enhanced auditory discrimination learning after progressive training and exposure. This enhanced auditory perceptual learning may help explain why these autistic children are socially impaired while retaining the capacity to learn language.

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7. Colwell K, Boianghu K, Komornik J, Brown S. Antipsychotic Treatment of Autistic Shutdowns-A Case Study. Psychopharmacol Bull;2025 (Apr 8);55(3):66-70.

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8. Conrad CE, Lauritsen MB, Færk E, Jakobsen H, Thomsen PH, George C. Representations of adult attachment and shame in parents of children on the autism spectrum. Front Psychol;2025;16:1519090.

Social communication disabilities in children on the autism spectrum challenge parenting. This is the first study to examine mental representations of adult attachment and shame in parents of children on the autism spectrum. Thirty-seven parents of children diagnosed with autism spectrum disorder (mean age 5.17 years) from middle to high-income households participated in the study. The Adult Attachment Projective Picture System was used to evaluate adult attachment patterns and representations as well as shame outcomes. All but three parents were classified as having insecure adult attachments. Almost half of the participants (45.9%) were classified as having unresolved attachments. All parents showed representations of a shamed self. Deep shame associated with attachment trauma was more common than normative shame. The sample was divided into regulated (secure, dismissing, and preoccupied combined) versus unresolved individuals. There were no significant group differences regarding shame or shame outcomes. The discussion addresses how the high frequency of insecure attachment representations and shame may affect parenting. This prevalence suggests that clinicians support families with children on the autism spectrum and introduce the topic of shame.

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9. Fazna A, Hagerman RJ. Prevalence of fragile X syndrome in South Asia, and importance of diagnosis. Med Rev (2021);2025 (Apr);5(2):164-173.

Fragile X syndrome (FXS) is a genetic disorder caused by a mutation in the FMR1 gene on the X chromosome, leading to a range of developmental and intellectual disabilities. FXS is characterized by intellectual disability, behavior challenges, and distinct physical features such as an elongated face, large ears, and hyperflexible joints; FXS remains the most common inherited cause of intellectual disability. Behavioral manifestations often include attention deficits, hyperactivity, anxiety, and features of autism spectrum disorder. The prevalence of FXS in the South Asian population is not well-documented, but existing studies suggest it may be comparable to global prevalence rates, which are approximately 1 in 4,000 males and 1 in 8,000 females. Accurate diagnosis of FXS in South Asians is crucial due to the implications for early intervention and treatment, which can significantly improve the quality of life and developmental outcomes for affected individuals. Early diagnosis also facilitates genetic counselling and family planning, helping to reduce the risk of recurrence in families. Increased awareness and screening in South Asian communities are essential to address the diagnostic gap and ensure timely support for individuals with FXS or disorders associated with the premutation of FMR1.

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10. Griffith MM, Stanek JR, Lemanek KL, Walden J, Nahata L, Creary SE. Prevalence and Impact of Autism Spectrum Disorder and Selected Neurodevelopmental Diagnoses in Hospitalized Youth With Sickle Cell Disease. Pediatr Blood Cancer;2025 (Apr 14):e31725.

BACKGROUND: Sickle cell disease (SCD) is a chronic illness accounting for 134,000 hospital admissions annually. Youth with SCD and youth with autism spectrum disorder (ASD) experience health disparities, yet the hospitalization outcomes of these youth have not been assessed. This study aimed to (i) determine the prevalence of ASD and selected neurodevelopmental disabilities (NDD) among hospitalized youth with SCD and (ii) compare hospitalization outcomes in youth with selected NDD and SCD to youth with SCD. PROCEDURE: ICD-10 diagnosis codes were used to identify admitted youth (2-18 year olds) with SCD, ASD, and selected NDD (i.e., developmental delay) in the Pediatric Health Information System (October 2015 to April 2024). Demographic (age, race) and clinical variables (length of stay, intensive care unit [ICU] admission, 30-day readmissions, hydroxyurea use, genotype) were assessed. RESULTS: Among 16,369 unique inpatients diagnosed with SCD (54.7% hemoglobin SS, median age = 11.9 years, and 86.4% non-Hispanic Black), 2.6% were diagnosed with a selected NDD; 1.7% were diagnosed with ASD. Hydroxyurea use during hospitalization did not differ between groups (3.3% vs. 3.5%; p = 0.19). Individuals with selected NDD had significantly higher annualized rates of hospitalization (0.88 vs. 0.65; p < .0001), ICU admission (0.12 vs. 0.05; p < .0001), and 30-day readmissions (20.2% vs. 17.4%; p = 0.0004) compared to youth without these neurodevelopmental diagnoses. The median length of stay in both groups was 3 days. CONCLUSIONS: Youth with selected NDD and SCD are at an increased risk of frequent and complicated hospitalizations. Additional research should investigate how inpatient and outpatient care delivery can be tailored and optimized to reduce the frequency and severity of hospitalizations.

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11. Herbers JE, Abdul-Masih M, Buccelli AR, Torre N, Pintarelli EM, Cutuli JJ. Developmental Screening and Family Resilience for Infants and Toddlers in Homeless Shelters. Infancy;2025 (Mar-Apr);30(2):e70019.

This study investigated motor and language development among infants and toddlers staying in family homeless shelters. We tested contributors to resilience and maladaptation, while also considering characteristics of developmental screening. Participants were 128 children (2-week to 35 months old; M = 8.54 months; 73% Black/African American) and their parents staying in eight urban family shelters. Data spanned time points about 2 months apart, involving an interview, parent-child play task, and a repeated, standardized observational screening measure. On average, this sample showed motor delays relative to age-based norms, and language delays for toddlers but not infants, a finding that may signal challenges in assessing language in young infants. Parent depression symptoms predicted lower gains in language, and parent education predicted higher gains in language. Positive parenting predicted gains in motor scores and a non-significant trend for language. We interpreted results as evidence of complex developmental processes of resilience and risk. Parent functioning is a key predictor of resilience and should be included in developmental screening of very young children who experience adversity. Shelter design, policy, and practices also should reflect consideration of early childhood development and parent empowerment.

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12. James A, Torres C, Carroll E, Elmongy H, Fricker G, Larkin O, Martin S, Pierre Francois J. Exploring Intersectionality in the Medical Care of a Latino Child With Autism. Hosp Pediatr;2025 (Apr 14)

Felix is a boy aged 10 years with autism and attention-deficit/hyperactivity disorder who presents to the pediatric emergency department for acute behavior change, including decreased interactivity, decreased speech, bruxism, and new urinary incontinence. He is admitted during the weekend, and scheduling of magnetic resonance imaging is delayed. Eventually, he has a computed tomography scan of his head, which shows an abnormal diffuse hypodensity involving the frontal lobe with extension into the cortex, all concerning for ischemia, and he is ultimately diagnosed with Moyamoya disease complicated by stroke. Felix and his family self-identify as Latino and Black and prefer to use a language other than English for medical discussions. Through this case, we (1) reflect on the barriers to clinical care faced by patients with autism; (2) define intersectionality and explore how neurodivergence, race, ethnicity, and parental-provider language discordance can augment and inhibit the provision of equitable care; and (3) discuss strategies that may mitigate the impact of oppression on clinical care.

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13. Jiang Z, Zhou Y, Zhou Y, Yang D, Li J, Li Y, Fan Q, Lin J. Exploring the bidirectional causal relationship between Autism Spectrum Disorder and Schizophrenia using Mendelian randomization. Medicine (Baltimore);2025 (Apr 11);104(15):e42119.

Autism Spectrum Disorder (ASD), characterized mainly by stereotyped behaviors and social impairments, affects about one in 100 children worldwide. Schizophrenia (SCZ), a chronic mental illness, affects 1% of the global population. The pathogenesis and specific treatment strategies for ASD and SCZ remain unclear. Previous research has suggested similarities in SCZ and ASD etiology and symptoms. However, no definitive correlation has been confirmed. Therefore, we conducted a Mendelian randomization study to assess the relationship between SCZ and ASD, providing new insights into their etiology and treatment. We used the two-sample Mendelian randomization (TSMR) approach to investigate the bidirectional causal association between SCZ and ASD, employing summary-level genome-wide association studies (GWAS) data. ASD summary data from the IEU GWAS database and SCZ summary data from the Psychiatric Genomics Consortium (PGC) were used as exposure and outcome variables, respectively. Statistical analysis was performed using the TwoSampleMR package in R version 4.3.2, with sensitivity analysis conducted to verify the result’s reliability. Based on the results of the MR analysis, we retrieved and analyzed the relevant genetic information from the GWAS Catalog. TSMR analysis revealed higher ASD risk in SCZ (IVW: OR: 1.19, 95% CI: 1.12-1.26, P < .001). Bidirectional MR analysis confirmed a causal relationship between ASD and SCZ (IVW: scz2018clozuk (Clozapine UK), OR: 1.12, 95% CI: 1.04-1.21, P = .003; scz2019asi, OR: 1.14, 95% CI: 1.05-1.23, P = .002). Our study demonstrated a bidirectional relationship between SCZ and ASD in the European population, suggesting that each may induce the onset of the other.

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14. Kang J, Mao W, Wu J, Li X. Measurement of Excitation-Inhibition Imbalance in Autism spectrum Disorder Using EEG Proxy Markers: A Pilot Study. Clin EEG Neurosci;2025 (Apr 13):15500594251333159.

Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder characterized primarily by social impairments and repetitive behaviors. Imbalance in excitatory-inhibitory (E/I) activity within the central nervous system may be a key mechanism underlying ASD. Electroencephalography (EEG) is a useful tool for recording brain electrical signals, reflecting the activity of cortical neuron populations, and estimating both global and regional E/I balance. Various EEG methods can estimate E/I balance, including non-periodic exponent, corrected alpha power, sample entropy, average spatial phase synchronization (ASPS), and detrended fluctuation analysis (DFA) based on E/I indices. However, research on using EEG proxy markers to assess E/I imbalance in autism is limited, and there is no study indicating which method is most sensitive. Therefore, this study employed a high-density EEG acquisition system to collect data from a relatively large sample of autistic and typically developing (TD) children. We computed EEG proxy markers and used the Coefficient of Variation (CV) to compare the sensitivity of five EEG markers between the two groups. The results indicated that non-periodic exponent based on power spectra and corrected alpha power from non-periodic neural activity were more advantageous. The findings may provide theoretical support for the exploration of EEG biomarkers based on E/I balance theory.

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15. Kim YS, Kwon S, Kim JH, Ho SH. Patterns of Mortality among People with Autism Spectrum Disorder in South Korea. Iran J Public Health;2025 (Feb);54(2):396-403.

BACKGROUND: Detailed statistics on the death status of persons with autism spectrum disorder (ASD) are lacking. We aimed to identify and compare recent mortality rates in persons with ASD in Korea. METHODS: From 2012 to 2021, databases were established by linking data on persons with ASD registered in Korea with data on cause of death from the National Statistical Office. RESULTS: Between 2012 and 2021, the mortality rate of persons with ASD and age-standardized mortality rates fluctuated annually. The crude mortality rates in the population with ASD were 91.6, 113.8, and 74.5 in 2012, 2016, and 2021, respectively, which were lower than the rates in the general population; however, the age-standardized mortality rate was observed to be five times higher. Intentional self-harm, as a cause of death in persons with ASD, was ranked high annually. The mortality rates in persons with ASD from diseases (50.7%) and injury (49.3%) were in a ratio of 1:1. Diseases and injury were more causes of death in males with ASD. The average age of persons with ASD at death was confirmed to be approximately 50 years lower than that of the general population. CONCLUSION: Deaths and causes of death in persons with ASD differ from those of the general population. Therefore, preventive measures and efforts are required to reduce avoidable deaths among persons with ASD.

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16. Li B, Xiong Y, Li Y. The Impact of Valproic Acid on Microbiota in a Mouse Model of Autism Spectrum Disorder. Psychiatry Clin Psychopharmacol;2025 (Mar);35(1):6-13.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neuropsychiatric condition with a multifactorial etiology, involving both genetic predisposition and environmental factors. Valproic acid (VPA), a commonly used antiepileptic drug, has been shown to induce ASD-like behaviors in rodent models, making it a valuable tool for studying the pathophysiology of ASD. This study aims to explore the effects of VPA on behavior and the microbiota in a mouse model of ASD. METHODS: C57BL/6 mice were used in this study, with pregnant females receiving a single intraperitoneal injection of VPA (450 mg/kg) or a saline solution on gestational day E12.5. Behavioral assessments, including the Three-Chamber Social Test, Elevated Plus Maze, Marble Burying Test, Open Field Test, and Light-Dark Box Test, were conducted on 8-week-old mice. Oral and fecal samples were collected for microbiota analysis, and gene expression profiling was performed on brain samples. RESULTS: VPA-treated mice exhibited significant deficits in social interaction, anxiety-like behaviors, and repetitive actions. Microbiota analysis revealed significant shifts in the composition of both oral and fecal microbial communities in VPA-treated mice, with reductions in alpha diversity and changes in the relative abundance of specific taxa. Gene set variation analysis of mice harboring VPA-induced microbiota identified notable discrepancies in metabolic pathways, suggesting that the dysbiosis may modulate the expression of genes involved in critical metabolic processes. CONCLUSION: The present study provides evidence that VPA exposure during early development can induce ASD-like behaviors in mice, along with significant changes in the composition of the microbiota. These findings underscore the complex interplay between environmental factors, such as VPA, and the microbiota in the pathophysiology of ASD. The study lays the groundwork for future research aimed at developing targeted interventions to mitigate the symptoms of ASD and other neuropsychiatric disorders, potentially through modulating the microbiota-gut-brain axis.

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17. Liu Z, Wang L, Yu L, Zhao Y, Zhu M, Wang Y, Cao A. Identification of immune cells and circulating inflammatory factors associated with neurodevelopmental disorders by bidirectional Mendelian randomization and mediation analysis. Sci Rep;2025 (Apr 14);15(1):12840.

The roles of various immune cells and circulating inflammatory factors in neurodevelopmental disorders (NDDs) remain controversial. Therefore we employed a two-sample and bidirectional Mendelian randomization and mediation method to explore the causal relationships between immune cells, circulating inflammatory factors, and NDDs. All data were originated from Genome-Wide Association Study (GWAS) datasets. We found a significant positive causal relationship between 13 immune cells and autism spectrum disorder (ASD), including six CD8+ T cells, one CD3+ T cell, two CD20+ B cells, one CD38+  B cell, and two plasmacytoid DC. 9 inflammatory factors showed significant causal relationships with ASD: interleukins-7 (IL-7), interleukins-2 (IL-2), Interleukin-2 receptor subunit beta levels( IL-2β) and interleukins-18 receptor 1 levels (IL-18-R1) were negatively associated. In contrast, five inflammatory factors were positively associated, such as tumor necrosis factor-α (TNF-α). 14 immune cells exhibited significant causal relationships with attention deficit hyperactivity disorder (ADHD). CD3 on naive CD8br and CD4 on activated Treg were positively associated, while four CD27-expressing B cells were positively associated with ASD. Four CD40-expressing monocytes were negatively associated with ADHD. 7 inflammatory factors had significant causal relationships with ADHD: Fibroblast Growth Factor 23 levels (FGF-23), CD40L receptor levels, Glial Cell Line-Derived Neurotrophic Factor levels (GDNF), TNF-α were more important among these. Mediation analysis identified 12 mediating relationships, with three showing strong evidence: Natural killer cell receptor 2B4 levels (19.9%), FGF-23 (11%), and Eotaxin levels (- 5.95%). Strong causal relationships existed between immune cells, circulating inflammatory factors, and NDDs. Inflammatory factors mediated the pathways between immune cells and NDDs.

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18. Looi MK. Trump watch: RFK Jr claims ignorance, NIH investigates autism origins, and more. Bmj;2025 (Apr 14);389:r757.

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19. Luo Q, Zeng X, Chen F, Kuang C. Emotional Prosody Recognition in Autism Spectrum Disorder Without Intellectual Disability: A Systematic Review and Meta-Analysis. J Autism Dev Disord;2025 (Apr 14)

Emotional prosody recognition is vital for social interaction and has become a key focus in autism research. However, findings regarding emotional prosody recognition in individuals with autism spectrum disorder without intellectual disability (ASD-without-ID) remain inconsistent. This study aims to address this inconsistency through a systematic review and meta-analysis, exploring potential factors that may account for the inconsistent results. A search across four major electronic databases identified 29 eligible studies comparing emotional prosody recognition in ASD-without-ID and typically developing (TD) participants. We identified several participant- and methodology-related moderators across these studies. Using a random-effects model, we found a moderate-to-large pooled effect (Hedges’ g = - 0.65) for emotional prosody recognition in ASD-without-ID participants, which remained stable after adjusting for publication bias through the trim-and-fill method. Emotional complexity and participant age significantly moderated the heterogeneity of effect sizes across studies. The results indicate moderate differences in the recognition of basic emotions through prosody between individuals with ASD-without-ID and TD individuals, with more pronounced differences for complex emotions. The findings emphasize the distinct developmental trajectories of ASD-without-ID individuals. We highlight the need for further investigation into the underlying factors and mechanisms affecting emotional prosody recognition in this population, including meta-analyses examining the moderate effects of various IQ measures and studies involving speakers of tonal languages.

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20. Ma J, Zhang H, Lv Y, Gao M, Gai Z, Liu Y. Clinical and Genetic Characteristics of Two Cases With Developmental and Epileptic Encephalopathy 93 Caused by Novel ATP6V1A Mutations and Literature Review. Hum Mutat;2024;2024:4678670.

Developmental and epileptic encephalopathy 93 (DEE93) is a new defined autosomal dominant neurologic disorder caused by heterozygous mutations in the ATP6V1A gene on chromosome 3q13. DEE93 is characterized by developmental delay, early-onset refractory seizures, hypotonia, and intellectual disability. So far, merely 31 cases caused by ATP6V1A gene mutation have been reported in literature worldwide, and early genetic detection is required for differential diagnosis. Here, we analyze the clinical and genetic features of two patients with two novel ATP6V1A mutations (c.1061G>T/p.(Trp354Leu) and c.746C>T/p.(Pro249Leu)) and expound the therapeutic schedule for epilepsy. We also review the reported mutations and genotypes associated with the disorder. Our study expands the clinical and genetic spectrum of ATP6V1A mutation-associated DEE93, which provides a basis for the diagnosis, treatment, and genetic counseling of the disorder.

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21. Mooney C, Parlante A, Canarutto G, Grigoli A, Scattoni ML, Ricceri L, Jimenez-Mateos EM, Sanz-Rodriguez A, Clementi E, Piazza S, Henshall DC, Provenzano G. Deregulated mRNA and microRNA Expression Patterns in the Prefrontal Cortex of the BTBR Mouse Model of Autism. Mol Neurobiol;2025 (Apr 14)

Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by both genetic and environmental factors. Since no single gene variant accounts for more than 1% of the cases, the converging actions of ASD-related genes and other factors, including microRNAs (miRNAs), may contribute to ASD pathogenesis. To date, few studies have simultaneously investigated the mRNA and miRNA profiles in an ASD-relevant model. The BTBR mouse strain displays a range of behaviors with ASD-like features but little is known about the protein-coding and noncoding gene expression landscape that may underlie the ASD-like phenotype. Here we performed parallel mRNA and miRNA profiling using the prefrontal cortex (PFC) of BTBR and C57BL/6 J (B6) mice. This identified 1063 differentially expressed genes and 48 differentially expressed miRNAs. Integration of mRNA and miRNA data identified a strong inverse relationship between upregulated (DEGs) and downregulated miRNAs, and vice versa. Pathway analysis, taking account of the inverse relationship between differentially expressed miRNAs and their target mRNAs highlighted significant shared enrichment in immune signaling, myelination, and neurodevelopmental processes. Notably, miRNA changes were predicted to affect synapse-related functions but we did not find enrichment of protein-coding genes linked to cellular components or biological processes related to synapses in the PFC of BTBR mice, indicating processes may evade miRNA control. In contrast, other miRNAs were predicted to have extensive relationships with DEGs suggesting their role as potential hub coordinators of gene expression. Profiling findings were confirmed via qRT-PCR for representative protein-coding transcripts and miRNAs. Our study underscores the complex interplay between gene expression and miRNA regulation within immune and inflammatory pathways in the BTBR model, offering insights into the neurodevelopmental mechanisms of ASD. These results support the value of the BTBR mouse model and identify strategies that could adjust molecular pathways for therapeutic applications in ASD research.

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22. Oner E, Kurutas EB, Altun H. Evaluation of Erythropoietin and Erythropoietin Receptor Levels in Children with Autistic Spectrum Disorder: Cross-sectional Study. Clin Psychopharmacol Neurosci;2025 (May 31);23(2):212-218.

OBJECTIVE: Autistic spectrum disorders (ASD) are a heterogeneous collection of neurodevelopmental disorders with an unknown etiology. Erythropoietin is a versatile growth factor that plays a crucial role in the nervous system, exhibiting high expression in various regions of the brain, including neurons, glial cells and endothelial cells. Recent animal studies have demonstrated that Epo exerts neuroprotective and neurotrophic effects. The objective of this study was to examine the levels of erythropoietin-(Epo) and its receptor-(EpoR) in children with ASD and to elucidate the potential effects of Epo in the disorder. METHODS: The study involved 50 children diagnosed with ASD based on the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders criteria, with ASD severity assessed using the Childhood Autism Rating Scale. Additionally, a control group of 50 healthy children was included. Serum samples were collected from both groups, and levels of Epo and its EpoR. RESULTS: There were no statistically significant differences between the age and sex distributions of the ASD and control groups (p > 0.05). However, analysis of the serum samples revealed a statistically significant reduction in Epo levels in the ASD cohort compared to the control. CONCLUSION: The results of our study indicate that Epo may have potential as an adjunctive therapy for children with ASD. The observed decrease in Epo levels and increase in EpoR levels in children with ASD suggest a dysregulation in the Epo-EpoR axis that may contribute to the pathophysiology of ASD. Further research is required to investigate the therapeutic effects of modulating Epo levels in ASD and to elucidate the mechanisms underlying these changes.

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23. Pokoski OM, Furnier SM, Gangnon RE, Howerton EM, Kirby AV, Protho T, Schweizer ML, Travers BG, Durkin MS. Prevalence of Motor Milestone Delays in Autistic Children. JAMA Pediatr;2025 (Apr 14)

IMPORTANCE: Prior literature has explored the prevalence of motor impairments in autistic individuals, but estimates come from clinical, convenience, or small samples, limiting generalizability. Better understanding of the frequency of motor milestone delays in autistic individuals could improve early identification and subsequently lead to earlier intervention and better developmental outcomes. OBJECTIVE: To determine the prevalence of motor milestone delays in a population-based sample of 8-year-old autistic children and to evaluate if having motor milestone delays is associated with an earlier age at autism evaluation or diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of autistic 8-year-old children was conducted using Autism and Developmental Disabilities Monitoring (ADDM) Network data between surveillance years 2000 and 2016. ADDM Network data are population based and are drawn from 17 sites across the US. Data were analyzed from October 2023 to August 2024. EXPOSURE: Binary indicator of motor milestone delays documented in health or educational records. MAIN OUTCOMES AND MEASURES: The primary outcome was the prevalence of motor milestone delays among autistic 8-year-old children. Associations between motor milestone delays and age at autism evaluation or diagnosis were evaluated using linear regression. Covariates included study site, surveillance year, the number of autism discriminators, intellectual disability, child sex, and child race and ethnicity. RESULTS: Among 32 850 children aged 8 years identified with autism by active surveillance, 23 481 children (71.5%) met criteria for motor milestone delays. A total of 5973 children (18.2%) were female. In linear regression models, children with motor milestone delays were evaluated for autism significantly earlier (mean age, 43.65 months; 95% CI, 43.38-43.91) than children without motor milestone delays (mean age, 51.64 months; 95% CI, 51.22-52.06). After stratifying by the co-occurrence of intellectual disability (ID), children with motor milestone delays were evaluated for autism earlier than those without motor milestone delays, regardless of ID. CONCLUSIONS AND RELEVANCE: This cross-sectional study estimates the prevalence of motor milestone delays among autistic 8-year-old children and highlights the association between these delays and an earlier autism evaluation, even in children without co-occurring ID. Early identification of autism is a public health priority, and assessing motor milestone delays, particularly in children with an increased likelihood of being autistic, may facilitate an earlier autism evaluation, leading to more timely interventions and better developmental outcomes.

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24. Scheithauer M, Vargas Londono F, Naugle B, Walker A, Hodnett JM, Lomas Mevers J, Muething C, Call N. Brief Report: Evaluating the Impact of Behavioural Concerns in Individuals With Intellectual or Developmental Disabilities. J Intellect Disabil Res;2025 (Apr 14)

BACKGROUND: Behavioural concerns, such as aggression and self-injury, are common among youth with intellectual and developmental disabilities. Additional research is needed to further explore the specific ways in which these types of behaviour impact individuals and their families. METHODS: Caregivers seeking treatment for their child’s behavioural concerns completed an interview regarding the negative impact of their child’s behaviour related to (a) physical harm to self or others, (b) property damage, (c) structural modifications, (d) situational avoidance and (e) reactive measures. We reviewed outcomes of these interviews to report on the prevalence of various negative impacts in this clinical sample. RESULTS: Most caregivers reported at least some physical harm (72.99%), property damage (63.99%) and preventative measures such as avoiding removing preferred items or activities (72.35%). Some caregivers endorsed severe negative impacts, such as the need for emergency services (10.61%) or residential placements (5.14%). CONCLUSIONS: Caregivers in this clinical sample consistently endorsed negative impacts resulting from behavioural concerns. This information is crucial in advocating for additional services for this high-need population, and the interview used to gather this information may be a helpful tool to guide future research and clinical work.

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25. Schnitzler T, Fuchs T. Autism spectrum disorder and schizophrenia: a phenomenological comparison. Front Psychiatry;2025;16:1546453.

A mental illness can lead to a distortion in a person’s capacity to engage with the world and other people in a variety of ways. This is particularly relevant to schizophrenia and autism spectrum disorder (ASD), which are not only historically linked, but also overlap clinically in several respects. From a phenomenological point of view, the differences or similarities between both disorders have not yet been sufficiently investigated. Schizophrenic autism can be characterized as a disorder of three interconnected dimensions, namely the self, intersubjectivity and the self’s relationship with the life-world. The present work therefore investigates differences in these three dimensions between the two disorders. One key difference is that the self-world relationship in schizophrenia can be described as unstable or fragmented, whereas in ASD it is considered stable. Finally, possible differences in the experience of delusions are discussed as a change in the self’s relationship with the world.

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26. Srinath S, Kalal A, Anand P, Mohapatra S, Chakraborty P. Small SNPs, Big Effects: A Review of Single Nucleotide Variations and Polymorphisms in Key Genes Associated With Autism Spectrum Disorder. Int J Dev Neurosci;2025 (Apr);85(2):e70016.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterised by significant genetic variation. This article examines genetic alterations linked to ASD, with a specific emphasis on single nucleotide polymorphisms (SNPs) and single nucleotide variants (SNVs). Recent genome-wide association studies (GWAS) have identified several genetic variations associated with ASD. Although their precise roles remain unclear, such genetic polymorphisms and variations significantly influence several neurodevelopmental processes. Mutations in SHANK3 and NRXN1, for example, disrupt synaptic activity and neurotransmission, contributing to ASD and intellectual deficits. Similarly, PTEN and MECP2, crucial for brain development, are associated with abnormal cell proliferation and neurodevelopmental disorders when mutated. CHD8, a key regulator of chromatin remodelling, is strongly linked to ASD, with its mutations impacting transcriptional regulation and neurodevelopment, while mutations in SCN2A disrupt neuronal excitability and synaptic transmission. In this review, we discuss SNPs and SNVs across these six key genes, to summarise their impact on the aetiology of ASD. A shift of focus in autism genetics giving equal importance to minor variations is critical to better understand the intricate aetiology of ASD and to create specific treatment strategies.

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27. Verdecias-Pellum N, Silverman C, Yudell M, Carroll-Scott A. Inequities in Community-Engaged Autism Research: Community Member Perspectives. Prog Community Health Partnersh;2025;19(1):25-34.

BACKGROUND: A history of exclusion and barriers to research participation exists for autistic individuals. Barriers to full community engagement have left under-engaged members of the autism community feeling isolated, frustrated, distrustful, and less informed about opportunities for research participation. OBJECTIVES: This study aimed to identify gaps in community-engaged research (CEnR) approaches in autism research by examining autism stakeholders’ (autistic adults, autism caregivers/parents, and service providers) perspectives about the risks, benefits and gaps in CEnR and suggestions on addressing the gaps related to autism research priorities. METHODS: Via qualitative narrative inquiry (n = 53), using a 16-item semi-structured instrument, we collected data from autism stakeholders representing different lived experiences and perspectives among autism communities. We primarily recruited via major autism advocacy and research organizations. Transcripts from a focus group (n = 6) and individual interviews (n = 47) were thematically coded. RESULTS: Participants expressed a lack of diverse representation in autism CEnR and in autism research subject populations. They suggested that an approach to community engagement that includes those often excluded from the process, and creates shared ownership in the decision-making process and a trusted platform for the autism community across demographic and diagnostic characteristics is important for understanding how to translate that information into effective and inclusive approaches. CONCLUSIONS: Autism stakeholders value research inclusivity, are interested in research participation, have the ability to make their own participation decisions with and without support from others (dependent on their preferences), and believe that research about adults with autism is important and beneficial towards addressing complex problems related to access to care.

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28. Verdecias-Pellum N, Silverman C, Yudell M, Carroll-Scott A. Inequities in Community-Engaged Autism Research: Community Member Perspectives. Prog Community Health Partnersh;2025;19(1):e5-e6.

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29. Wolfer P, Baumeister F, Cohen D, Dimitrova N, Solaimani E, Durrleman S. Co-speech gesture comprehension in autistic children. J Child Lang;2025 (Apr 14):1-22.

Co-speech gestures accompany or replace speech in communication. Studies investigating how autistic children understand them are scarce and inconsistent and often focus on decontextualized, iconic gestures. This study compared 73 three- to twelve-year-old autistic children with 73 neurotypical peers matched on age, non-verbal IQ, and morphosyntax. Specifically, we examined (1) their ability to understand deictic (i.e., pointing), iconic (e.g., gesturing ball), and conventional (e.g., gesturing hello) speechless video-taped gestures following verbal information in a narrative and (2) the impact of linguistic (e.g., vocabulary, morphosyntax) and cognitive factors (i.e., working memory) on their performance, to infer on the underlying mechanisms involved. Autistic children displayed overall good performance in gesture comprehension, although a small but significant difference advantage was observed in neurotypical children. Findings suggest that combining speech and gesture sequentially may be relatively spared in autism and might represent a way to alleviate the demand for simultaneous cross-modal processing.

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30. Yang M, Wang J, Zhou Z, Li W, Verkhivker G, Xiao F, Hu G. Machine Learning and Structural Dynamics-Based Approach to Reveal Molecular Mechanism of PTEN Missense Mutations Shared by Cancer and Autism Spectrum Disorder. J Chem Inf Model;2025 (Apr 14)

Missense mutations in oncogenic proteins that are concurrently associated with neurodevelopmental disorders have garnered significant attention. Phosphatase and tensin homologue (PTEN) serves as a paradigmatic model for mapping its mutational landscape and identifying genotypic predictors of distinct phenotypic outcomes, including cancer and autism spectrum disorder (ASD). Despite extensive research into the genotype-phenotype correlations of PTEN mutations, the mechanisms underlying the dual association of specific PTEN mutations with both cancer and ASD (PTEN-cancer/ASD mutations) remain elusive. This study introduces an integrative approach that combines machine learning (ML) with structural dynamics to elucidate the molecular effects of PTEN-cancer/ASD mutations. Analysis of biophysical and network-biology-based signatures reveals a complex energetic and functional landscape. Subsequently, an ML model and corresponding integrated score were developed to classify and predict PTEN-cancer/ASD mutations, underscoring the significance of protein dynamics in predicting cellular phenotypes. Further molecular dynamics simulations demonstrated that PTEN-cancer/ASD mutations induce dynamic alterations characterized by open conformational changes restricted to the P loop and coupled with interdomain allosteric regulation. This research aims to enhance the genotypic and phenotypic understanding of PTEN-cancer/ASD mutations through an interpretable ML model integrated with structural dynamics analysis. By identifying shared mechanisms between cancer and ASD, the findings pave the way for the development of novel therapeutic strategies.

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