1. Albantakis L, Weindel L, Brandi ML, Zillekens IC, Henco L, Thaler H, Schliephake L, Schilbach L. Alexithymic and autistic traits differentially predict personality disorder dimensions. Autism;2025 (Jun 1):13623613251338650.

Alexithymia and autism are variably characterized by social cognitive and perceptual deficits, which can lead to profound social interaction difficulties. Such difficulties are also the hallmark of personality disorders (PDs), but the potential link between alexithymia, autism, and PDs remains unclear. Here, we investigated whether autistic and/or alexithymic traits are associated with specific PD dimensions as measured by the Assessment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Personality Disorders Questionnaire (ADP-IV). We included individuals with a formal autism diagnosis (AP, n = 89), individuals with a psychiatric diagnosis other than autism (NAP, n = 51), and neurotypical participants (NPs, n = 84). We applied linear regression analyses with autistic and alexithymic traits as predictors and PD dimensions as outcome variables, while controlling for age, depressive, and socially anxious symptoms. While autistic traits predicted the obsessive-compulsive PD dimension, alexithymic traits predicted the borderline PD dimension. Autistic and alexithymic traits were both significant predictors of the schizoid PD dimension. Taken together, our results point toward overlaps between autistic traits and specific PD dimensions that are well recognized as differential diagnoses of autism, while alexithymia was differentially linked to the borderline PD dimension.Lay abstractAutistic people have trouble identifying their own emotions and others’ emotions. They also struggle to describe their emotions. People with alexithymia have similar difficulties. This can make it hard for autistic and alexithymic people to react appropriately to situations. Some may avoid places, while others may start overthinking. This can lead to patterns of behavior and thinking that limit us in our daily lives. If these patterns become a part of our personality, we may develop a personality disorder (PD). In our study, we looked at whether autistic and alexithymic people have certain PD dimensions. We included autistic participants, non-autistic participants with social-interactive difficulties, and non-autistic participants without social-interactive difficulties. We found that autistic features were linked to obsessive-compulsive PD dimension. Alexithymic features were linked to borderline PD dimension. Autistic and alexithymic features were linked to schizoid PD dimension. Our results point toward overlaps between autistic traits and PD dimensions that are well recognized as differential diagnoses of autism. The exception was borderline PD dimension, which was linked to alexithymic traits.

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2. Bottema-Beutel K, Guo R, Hinson-Wiliams J, Shen Y, LaPoint S, Woynaroski T, Sandbank M. Research Review: Conceptualizing and measuring ‘problem behavior’ in early intervention autism research – a project AIM secondary systematic review. J Child Psychol Psychiatry;2025 (Jun 1)

BACKGROUND: Some autistic children exhibit behavior that caregivers, clinicians, and researchers consider problematic. However, there is little consensus about the types of behaviors that should be treated as a problem and reduced via intervention. In autism intervention research, problem behaviors range from inherently harmful behaviors such as aggression and self-injury to nonnormative but not harmful behaviors associated with autism such as repetitive movements. Likewise, there are a variety of conceptualizations and measurement practices used to assess these behaviors. METHODS: In this secondary systematic review of group-design, nonpharmacological intervention studies for autistic children up to age eight, we explore researchers’ conceptualizations of problem behavior and measurement systems to assess problem behavior. We defined problem behavior as any outcome where behaviors were targeted for reduction or elimination. A coding scheme was applied to 102 studies that met inclusion criteria for the secondary review. All studies were double coded by two independent coders. RESULTS: Sixty-two percent of studies described reducing behavior as a primary or secondary purpose of the study and/or intervention, 33% gave a rationale for targeting behaviors for reduction, and 28% offered a conceptualization of the behavior(s) they targeted. Only 8% offered a conceptual definition. The most common measures were ‘off-the-shelf’ measures that had undergone at least some previous validation beyond interrater reliability and that involved parent reports. For the 10 most common assessment measures, two were validated along six different validation dimensions in autistic populations. All but one full scale or subscale measured behaviors that were nonnormative but not inherently harmful, or a mix of behaviors that were inherently harmful and that were nonnormative but not inherently harmful. CONCLUSIONS: Intervention researchers should provide clear definitions and rationales for targeting behaviors for reduction via intervention and should develop refined measurement tools for assessing these behaviors in collaboration with the autistic community.

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3. Çalışkan G, Lacalle SE, Kul E, Del Ángel M, Zambrano AL, Hukema R, Santos M, Stork O. Modelling fragile X-associated neuropsychiatric disorders in young inducible 90CGG premutation mice. Brain;2025 (Jun 2)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a preCGG repeat expansion in the FMR1 gene. Individuals with the FMR1 premutation often exhibit neuropsychiatric symptoms before FXTAS onset, leading to the identification of fragile X-associated neuropsychiatric disorders (FXAND). Rodent models of FXTAS show motor impairments, pathological intranuclear inclusions, and heightened anxiety. However, the early onset of neuropsychiatric features and underlying mechanisms remain poorly understood. To address the above issues, we used the doxycycline (dox)-inducible 90CGG mouse model, with transgene activation at two developmental stages: adolescence and young adulthood. Mice were evaluated in a behavioural battery to assess anxiety-like behaviour, exploration, and motor coordination and learning. Next, we conducted a combination of ex vivo extracellular local field potential recordings to measure synaptic physiology and oscillatory activity in the limbic system, particularly in the basolateral amygdala (BLA) and ventral hippocampus (vH) regions. Parvalbumin interneurons and intranuclear inclusions in the amygdala and hippocampus were investigated by immunofluorescence, while mass spectrometry and gene set enrichment were used to identify differentially expressed proteins molecular pathways. Adolescent 90CGG mice displayed early-onset hyperactivity, transitioning to heightened anxiety in young adulthood, coinciding with the accumulation of intranuclear inclusions in the BLA and vH. Electrophysiological analysis revealed augmented gamma oscillations in the vH, emerging during adolescence and persisting in young adulthood. These changes correlated with a reduction in parvalbumin interneurons in these regions, and together likely contribute to enhanced BLA excitability and impaired vH plasticity. Finally, proteomic analysis of the vH revealed altered proteins linked to attention deficit hyperactivity disorder in adolescence and anxiety/depression in adulthood, aligning well with behavioural findings. Importantly, these behavioural, electrophysiological, and cellular alterations were reversible upon transgene inactivation. This study reveals a temporal progression of CGG premutation effects on behaviour, from hyperactivity to heightened anxiety to late onset motor dysfunction. Moreover, these findings provide altered network activity in the limbic system as a putative mechanism in neuropsychiatric features of premutation carriers.

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4. Chen H, Yang T, Chen J, Ding Y, Xiang X, Wei Q, Mou Q, Yuan B, Hu B, Zhang D, Ai D, Li T. Social jet lag is associated with core symptoms in 2-3-year-old children with autism spectrum disorders. Front Psychiatry;2025;16:1574814.

BACKGROUND: Social jet lag (SJL) is a form of circadian rhythm misalignment caused by the mismatch between social schedules and biological clocks, which is associated with cognition, behavior, and emotion in children. However, social jet lag among children with autism spectrum disorders (ASD) and its impacts are unknown. METHODS: This cross-sectional study recruited 2-7-year-old children with ASD from special education institutions and outpatient clinics. The Children’s Sleep Habits Questionnaire (CSHQ) assessed children’s sleep. SJL was calculated as |weekend sleep midpoint – weekday sleep midpoint|. Sleep adequacy was determined based on the National Sleep Foundation’s recommendations. Core symptoms were evaluated using the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC). Developmental level was assessed using the Gesell Developmental Scale. RESULTS: 1) The prevalence of sleep problems was 49.8% and the mean CSHQ total score was 48.04 in ASD. There are significant differences in sleep patterns between weekends and weekdays, characterized by later bedtimes, delayed wake-up times, increased total sleep duration, and reduced prevalence of sleep deficiency during weekends. 2) The 2-3-year-old group had the highest rates of sleep insufficiency (80.77% on weekdays; 82.17% on weekends). There were no significant differences in sleep duration across different age groups, with the median sleep duration ranging from 9.5 to 10 hours. 3) Median SJL in each age group was 0.25 h (2-3 years), 0.5 h (3-4 years), 0.42 h (4-5 years), and 0.5 h (≥5 years), respectively. In children aged 2-3 years, SJL was significantly positively correlated with core symptoms 4) SJL was observed to be weakly associated with developmental level of personal-social only in the ≥ 3-year-old group (r = 0.100, P = 0.042). CONCLUSION: Our study found for the first time a correlation between SJL and core symptoms in 2-3-year-old children with ASD. This finding suggests that SJL may have a potentially negative impact on core symptoms in ASD. Therefore, it is crucial to emphasize the importance of regular routines for ASD, especially in younger children.

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5. Ebrahimiazar S, Kikkawa T, Minakuchi Y, Miyashita S, Manabe S, Hoshino M, Toyoda A, Osumi N. A Transcriptomic Dataset of Embryonic Murine Telencephalon of Fmr1-Deficient Mice. Sci Data;2025 (Jun 2);12(1):927.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene. FXS patients exhibit autistic behaviors and abnormal brain structures, with notable sex differences. However, the mechanisms by which Fmr1 deficiency leads to these sex differences during brain development remain unclear. In this study, we performed bulk RNA sequencing on telencephalon samples of Fmr1-knockout mice of both sexes at embryonic day (E) 14.5, i.e., at the peak of neurogenesis. Clustering analysis revealed gene expression differences influenced by Fmr1 gene dosage and sex. We found that majority of the transcripts were shared between male and female sample groups, while a smaller number were unique to each sex. Our dataset underscores the importance of studying brain development during the embryonic period to detect sex-dependent genetic factors which contribute to neurodevelopmental disorders.

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6. Haebig E, West S, Jiménez E, Hills TT, Cox CR. Network Analysis of Autistic Language Learners Along the Small World Spectrum. Autism Res;2025 (Jun 2)

Recent network analyses of vocabulary growth revealed important relationships between the structure of the semantic environment and early vocabulary acquisition in non-autistic children. However, autistic children may be less likely to encode associated features of novel objects, suggesting divergent processes for acquiring semantic information about words. We examined the expressive vocabularies of 815 non-autistic and 163 autistic children (words produced: M(Autistic) = 183.06, M(Non-autistic) = 182.91). We estimated their trajectories of semantic development using network analyses. Network structure was based on child-oriented word associations. We analyzed networks according to indegree, average shortest path length, clustering coefficient, and small-world propensity (features holistically contributing to « small-world » network structure). Analyses revealed that autistic and non-autistic children are sensitive to the structure of their semantic environment. However, group differences were observed, with an early peak in the autistic group’s clustering coefficient (how closely connected groups of words are), followed by a sharp decline. Moreover, across each network metric, we found that autistic children had reduced small-world structure relative to non-autistic toddlers. Thus, group differences indicate that, although autistic children are learning from their semantic environment, they may be processing their semantic environment differently, the language input to which they are exposed differs relative to non-autistic children, or a combination of the two.

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7. Laguna GGC, Gusmão ABF, Marques BO, Bragas N, Rodrigues IB, Melo RS, de Azevedo KRM. Neuroplasticity in autism spectrum disorder: a systematic review. Dement Neuropsychol;2025;19:e20240182.

The brain’s ability to adapt in response to stimuli is called neuroplasticity. OBJECTIVE: This study investigates neuroplasticity in autistic individuals, focusing on neurobiological aspects, clinical correlations, and therapeutic interventions. METHODS: This systematic review, registered in the International Prospective Register of Systematic Reviews-PROSPERO (ID: CRD42024522425) and guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses-PRISMA (2020) criteria, searched databases like Web of Science, Scopus, United States National Library of Medicine/ Medical Literature Analysis and Retrieval System Online (PubMed/Medline), Latin American and Caribbean Health Sciences Literature (LILACS), and Scientific Electronic Library Online (SciELO) for original articles published in 2018-2023. RESULTS: Of the 2,316 studies found, 11 were selected, involving 1,943 autistic individuals, both children and adults. Most studies were classified as high/moderate quality using the Newcastle-Ottawa and Jadad scales. Observations included variations in SHANK2 gene expression, lower concentrations of α-synuclein, higher β-synuclein in children with autism spectrum disorder (ASD), correlations between NCAM1 expression and motor skills, and higher brain-derived neurotrophic factor (BDNF) concentration compared to non-autistic children. CONCLUSIONS: Alterations in SHANK2, α-synuclein, β-synuclein, NCAM1, and BDNF in ASD suggest biomarkers and therapeutic targets for more effective interventions, improving care for autistic individuals.

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8. Liu L, Xie L, Shen Y, Zeng Z, Xu D, Bo L, Wu L, Wu Y, Zhang Y, Wang Y, Pi J, Chen X, Wang R, Yang X, Wei X, Liu H, Tang Y. Reduced exosomal miR-215-5p activates the NEAT1/MAPK1/p-CRMP2 pathway and contributes to social dysfunction in a VPA-induced autism model. Neuropharmacology;2025 (Jun 2);278:110539.

Autism is a prevalent neurodevelopmental disorder characterized by social deficits. Environmental factors, such as prenatal exposure to valproic acid (VPA), are major risk factors for the development of autism in offspring. Environmental epigenetics investigates how environmental factors influence gene expression and function. Exosomal miRNAs carry epigenetic information, but their role in autism remains unknown. Here, we found that prenatal VPA exposure reduced the majority of exosomal miRNA expressions in male newborn amygdala tissue, with exosomal miR-215-5p showing the highest decline. Reduced exosomal miR-215-5p increased neuronal lncRNA NEAT1 expression. Overexpressed neuronal NEAT1 increased the recruitment of the HSP90AB1-MAPK1-CRMP2 complex, which elevated phosphorylated CRMP2 (p-CRMP2) levels. Enhanced p-CRMP2 acted as an « eat me » signal to microglia, resulting in excessive synaptic pruning and aberrant synaptic maturation. Increasing neuronal p-CRMP2 levels via phosphorylation virus T514E or overexpression of MAPK1 promoted microglial synaptic pruning, leading to synaptic defects and social dysfunction. Furthermore, NEAT1 silencing or MAPK1 inhibition reversed the elevated p-CRMP2 levels in VPA-exposed offspring, hence preventing excessive synaptic pruning and social dysfunction. These findings suggested that prenatal VPA exposure reduced exosomal miR-215-5p and activated NEAT1/MAPK1/p-CRMP2 pathway, which resulted in abnormal synaptic development and social interaction disorders.

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9. Martínez-Cayuelas E, García-Muñoz AM, de Ocaña-Moreno MLS, Richdale AL, Gisbert-Gustemps L, Lugo-Marín J, Rodríguez-Morillas B, Peiró-Peiró AM, Victoria-Montesinos D, López-Anguas C, Meseguer-Illán MD, Ballester-Navarro P. Sleep-Wake Cycle and Circadian Misalignment in People With Autism Across the Lifespan With an Emphasis on Living Conditions. Autism Res;2025 (Jun 2)

Sleep problems among individuals with autism spectrum disorder (ASD) are a persistent issue that spans from early childhood to adulthood. The present study aimed to objectively investigate sleep continuity and alignment using ambulatory circadian monitoring (ACM) in a group of autistic individuals, with and without intellectual disabilities. We studied 214 participants. Sleep continuity and alignment were assessed using a minimum of 3 days of ACM. Participants were divided into four groups: (1) age < 10 years (n = 40, 87.5% males, M = 6.78 ± 1.40 years), (2) age 10-17 years (n = 53, 90.6% males, M = 12.62 ± 2.04 years), (3) age 18-27 years (n = 59, 74.6% males, M = 23.50 ± 2.60 years), and (4) age 28-65 years (n = 62, 74.2% males, M = 39.04 ± 9.49 years). All groups had significantly impaired sleep outcomes, except for TST. Adults had longer SOL and WASO duration, than children and adolescents. However, those differences were attenuated if participants 'percentages of sleep parameters within normal range' were compared. When evaluating circadian misalignment, sleep M5 is delayed in children and adolescents (2:56 am and 3:00 am, respectively), and strongly advanced in the older adults (group 4). Sleep problems that manifest in autism during childhood can endure throughout adulthood. Furthermore, there is a necessity to investigate how living conditions, such as enforced schedules in residential facilities, can influence the timing of the sleep midpoint.

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10. Morita R, Kato K, Nagashima R, Momose M, Mori S, Kondo M. Vitamin A deficiency presenting with ptosis and optic neuropathy in child with autism spectrum disorder. Doc Ophthalmol;2025 (Jun 1)

PURPOSE: To report our findings in a rare case of vitamin A deficiency (VAD) in a 5-year-old boy who presented with ptosis and exotropia. METHODS: Comprehensive ophthalmological examinations including full-field electroretinography (ff-ERG), optical coherence tomography, and magnetic resonance imaging were performed. RESULTS: The decimal visual acuity was 0.02 in both eyes at the initial examination. Ophthalmological examinations revealed bilateral corneal opacities, conjunctival keratinization, and exotropia. The scotopic ff-ERGs were extinguished and the photopic ff-ERGs were significantly reduced. Blood tests confirmed severe VAD of ≤ 5 IU/dL (normal range, 97-316 IU/dL). Optical coherence tomography (OCT) showed a thinning of the retinal nerve fiber layer, and MRI suggested a narrowing of the optic nerve canals. A detailed medical history identified autism and a highly selective eating habit limited to white rice. Oral vitamin A supplementation (0.6 g/day) and zinc acetate (25 mg/day) were initiated. Within one month, the corneal epithelial defects had resolved, and the ptosis improved. One year and three months post-treatment, the scotopic and photopic ff-ERGs were markedly improved. However, the OCT and visual evoked potential findings indicated a persistent optic neuropathy. CONCLUSIONS: This case underscores the effect of irreversible optic neuropathy due to delayed VAD diagnosis and treatment in a pediatric patient. An early detailed dietary history, electrophysiological screening, and appropriate supplementation are critical tasks that are needed to lessen the risk of irreversible visual impairment in pediatric VAD cases.

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11. Mysore A, Kaku SM. Predictors of Outcome in Autism Spectrum Disorders: A Perspective for Clinicians and Therapists. Indian J Psychol Med;2025 (May);47(3):290-294.

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12. Nadwodny N, Yoder PJ, Ingersoll BR, Wainer AL, Stone WL, Eisenhower A, Carter AS. The Language ENvironment Analysis (LENA) System in Toddlers With Early Indicators of Autism: Test-Retest Reliability and Convergent Validity With Clinical Language Assessments. Autism Res;2025 (Jun 2)

Clinical language assessments often influence the types of services that autistic children are eligible to receive. However, these assessments often take place outside of the child’s natural language environment. In this study, we assess the potential of using naturalistic language processing technology, the Language ENvironment Analysis (LENA) system, in clinical research. Within a sample of caregivers and autistic toddlers aged 16-33 months (N = 100), the current study examined associations between all LENA-generated variables and two clinical assessments of language: the Vineland Adaptive Behavior Scales, Third Edition: Communication Domain and the MacArthur Bates Communicative Development Inventories: Vocabulary Checklist. We also evaluated LENA test-retest reliability in a subsample of participants (n = 81). Some LENA-generated variables-specifically, the Conversational Turn Count, Vocal Productivity, and Automated Vocalization Assessment-exhibited small-to-moderate significant positive correlations with clinical language assessment variables. Additionally, all LENA-generated variables demonstrated moderate-to-good test-retest reliability within a 2-week period. To our knowledge, this is the first study that examines the psychometric properties of all LENA-generated variables in a single large sample. Findings show promising evidence of LENA’s utility as a source of naturalistic language data for research with autistic toddlers. Trial Registration: ClinicalTrials.gov identifier: NCT05114538 (« Improving the Part C Early Intervention Service Delivery System for Children with ASD »).

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13. Niro J, Zubairi MS, Leung JS. Improving the care of children with autism and related neurodevelopmental disorders in emergency department settings: Understanding the knowledge-to-practice continuum of emergency department providers. Paediatr Child Health;2025 (May);30(2):60-67.

OBJECTIVES: Emergency department (ED) healthcare providers (HCPs) frequently describe a lack of knowledge in caring for children with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). Our primary objective is to explore gaps in training and clinical exposure reported by ED HCPs caring for children with ASD/NDD. METHODS: A two-phase, mixed-methods cross-sectional study was conducted. In phase 1, an interprofessional sample of tertiary care paediatric ED HCPs (physicians, nurses, social workers, and child life specialists) were surveyed about their experiences and perceived gaps in managing children with ASD/NDD. These responses informed phase 2, where six semi-structured interviews were conducted. Interview transcripts were analyzed to determine themes around the discomfort of ED HCPs caring for children with ASD/NDD. RESULTS: The majority, 54/78 (69%) of eligible staff completed the survey. A minority (42.5%) of HCPs had mandatory training on ASD/NDD, and 80% would value continuing education. Some ED HCPs (41.2%) had previous personal or professional experiences with children with ASD/NDD that facilitated deeper empathy and awareness of system challenges. Interviews revealed four themes of ED HCP discomfort with this population: 1) added considerations of interacting with children and families with ASD/NDD; 2) the ED as a single touch point in complex and limited healthcare systems; 3) recognizing comfort in discomfort; and 4) the need to implement practical interventions to improve care. CONCLUSIONS: ED HCPs are motivated to improve care for children with ASD/NDD. Alongside broader systems interventions, future educational interventions can narrow ED HCP gaps identified through this work.

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14. Pan R, Bi Y, Zhou S, Tian Z, Xu A. Association between anesthetics and autism spectrum disorder: from bench to bedside. J Anesth;2025 (Jun 2)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms of impaired social communication and stereotyped behaviors. While early-life exposure to anesthetics may increase the risk of ASD, anesthetics can also have therapeutic effects on ASD, potentially through mechanisms involving the N-methyl-D-aspartate (NMDA) receptor, gamma-aminobutyric acid (GABA)ergic, and µ-opioid receptor signaling pathways. Given that individuals with ASD often exhibit high levels of non-cooperation and poor communication abilities, they typically require deeper sedation during medical examinations, making the choice of anesthetics particularly critical. This article provides an overview about the effects and underlying mechanisms of various anesthetics with ASD, aiming to assist anesthesiologists in implementing anesthesia management for ASD patients more scientifically.

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15. Rahman M, Noman AA, Saba AA, Adiba M, Hasan MM, Yasmin T, Ahmed B, Ebihara A, Nabi A. Genetic Variants Within ND2 Gene of Mitochondria are Associated with the Altered Levels of Ammonia, Vitamin D and Free Thyroxine in Bangladeshi Children with Autism Spectrum Disorder. Biochem Genet;2025 (Jun 1)

Autism spectrum disorder (ASD) is a complex and multifaceted neurodevelopmental disorder that is becoming more common worldwide. While there is growing evidence linking mitochondrial dysfunction to ASD, the exact causes remain unclear. There is little study being done in Bangladesh on the genetic and biochemical causes of ASD. The goal of this study is to identify mitochondrial DNA (mtDNA) variants in the ND2 gene and explore how these variations might be linked to the progression of ASD and biochemical parameters. Eighty children aged 2-10 years were enrolled, comprising 50 ASD children and 30 healthy controls. Biochemical parameters (lactic acid, ammonia, ALT, AST, calcium, magnesium, TSH, vitamin D, and free thyroxine or FT4) were tested, and mtDNA was extracted and amplified for Sanger sequencing. Identified single nucleotide polymorphisms (SNPs) were evaluated for association with disease outcome and biochemical parameters. Bioinformatics tools were used to analyze the impact of SNPs on protein structure and function. The findings demonstrated significant differences in lactic acid, ammonia, ALT, AST, vitamin D, and FT4 levels between the ASD and control groups (p < 0.05). Lactic acid (AUC = 0.993) showed the highest diagnostic accuracy, while ammonia (AUC = 0.899), AST (AUC = 0.884), and vitamin D (AUC = 0.863) showed excellent performance. A total of 37 SNPs were identified in the ND2 gene, three were novel, with 4901 A>G, 5124 C>A, and 5306 C>T. No variant was found to be associated with disease outcome. However, variants located at 5108 T>C, 5262 G>A, 4703 T>C, 4841 G>A, and 5186 A>T were found to be significantly associated with the altered levels of ammonia, vitamin D and FT4, respectively. Among three novel variants, two were synonymous SNPs (4901 A>G and 5306 C>T) and they showed decreased RSCU values, indicating lower efficiency and affect gene expression. Three variants were identified within the tRNA specific for Q and M but they were predicted to be likely benign. Comprehending the association of these genetic variations and biochemical markers with ASD should facilitate early detection and subsequent management strategy in children with these neurodevelopmental disorders.

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16. Ricci MF, Phung R, Zwaigenbaum L, Hanlon-Dearman A, Burns J, Narvey S, Urquia ML. Autism and immigration, is there a link? Results from a Manitoba Study. Paediatr Child Health;2025 (May);30(2):68-72.

OBJECTIVES: To examine a possible association between parental immigration and autism spectrum disorder (ASD) in Manitoba, Canada. METHODS: Electronic medical records of children diagnosed with ASD between 2016 and 2021 at Manitoba’s only publicly funded referral site for ASD evaluation in children ≤6 years of age were reviewed. Children born in or outside of Canada whose parents/guardians (one or both) were foreign-born were identified to have ‘immigrant’ parents. The proportion of Manitoba’s immigrant population (including non-permanent residents) was obtained from 2016 to 2021 Census data and compared to the proportion of children diagnosed with ASD who had immigrant parent(s). Descriptive statistics were used to compare the characteristics of children with ASD born to immigrants versus non-immigrant parents. RESULTS: Among 1858 children diagnosed with ASD during the study period, 669 (36%) had immigrant parents. This proportion was greater than the proportion of immigrants (and non-permanent residents) living in Manitoba in 2016: 243,835/1,278,365 (19%, P < 0.001) and 2021: 291,910/1,342,153 (21.7%, P < 0.001). Those with immigrant parents had a lower rate of family history of ASD (16.3% versus 33.3% P < 0.001), and associated neurologic comorbidities (4.2% versus 6.4% P: 0.047). There were no statistical differences in rates of preterm birth (15.5% versus 12.36 P: 0.152) or use of Autism Diagnostic Observation Schedule-2 in diagnostic approach (30.3% versus 33% P: 0.321) between groups. CONCLUSIONS: There is an over-representation of immigrant families among young children diagnosed with ASD in Manitoba. Further studies are needed to understand mechanisms that may play a role in this association.

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17. Shin D, Cho E, Park K, Chung C, Kim DH, Jeon SJ, Shin CY. Early postnatal exposure to bicuculline modulates E/I balance and induces ASD-like behavioral phenotypes in mice. Anim Cells Syst (Seoul);2025;29(1):264-281.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive behaviors. While precise causes of ASD remain elusive, growing evidence highlights that an imbalance in excitatory and inhibitory (E/I) signaling is a pivotal factor in ASD development and modulation. Balanced E/I neurotransmission is critical for circuit formation, synaptic plasticity, and developmental timing. However, key questions persist, including the critical perturbation window, neurological and neurodevelopmental effects, and clinical implications of E/I imbalance. This study investigated early-life modulation of the GABAergic system’s impact on E/I balance and ASD-like behaviors in mice. Mice were treated with bicuculline, a GABAA receptor antagonist, from postnatal days 7-11, and behavioral tests were conducted during adolescence. Results revealed deficits in social interaction in both male and female mice and increased repetitive behaviors in bicuculline-treated male mice. Electrophysiological recordings in the mPFC indicated reduced resting membrane potential, heightened neuronal excitability, and a shift in the E/I ratio. In the hippocampus, recordings displayed enhanced LTP and altered synaptic plasticity. DEG analysis of the PFC in bicuculline-treated mice unveiled aberrant gene profiles related to the regulation of synaptic function. Clinical significance and underlying mechanisms of abnormal brain activity, neurodevelopment, and ASD-related behaviors prompted by neonatal bicuculline treatment require further investigation. Nevertheless, these results suggest that GABAergic signaling disruption during the neonatal period might contribute to ASD-related brain pathophysiological changes.

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18. Tao X, Li Z, Wang D, Pu J, Liu Y, Gui S, Zhong X, Yang D, Zhou H, Tao W, Chen W, Chen X, Chen Y, Chen X, Xie P. Perturbations in gut microbiota in autism spectrum disorder: a systematic review. Front Neurosci;2025;19:1448478.

BACKGROUND: Autism spectrum disorder (ASD) is a neurological and developmental disorder commonly accompanied by gut dysbiosis and gastrointestinal symptoms. Accumulating evidence supports a crucial role of gut microbiota dysbiosis in the pathophysiological mechanisms of ASD. However, the alteration of gut microbiota shows high heterogeneity across different studies. This study aims to identify potential biomarkers in the gut microbiota of patients with ASD. METHODS: We conducted a comprehensive analysis by searching the PubMed, Web of Science, Cochrane Library, and Embase databases, for studies assessing the changes of gut microbial diversity and taxa in ASD patients and healthy controls using high-throughput sequencing. Vote counting analyses were performed to identify consistently altered gut microbes associated with ASD. RESULTS: Sixty-four studies involving 189 differentially abundant gut microbial taxa were included. Our synthesis provided no strong evidence for a difference in α-diversity between ASD patients and healthy controls, while studies were relatively consistent in reporting differences in β-diversity. Among 189 taxa, we identified three significantly increased taxa in ASD patients: Eubacteriales, Klebsiella, and Clostridium. Additionally, there were enriched trends of Oscillospira, Dorea, and Collinsella, and depleted trends of Streptococcus, Akkermansia, Coprococcus, and Dialister. These findings suggest that the disrupted intestinal microecology and functional changes in ASD are characterized by an enrichment of pro-inflammatory genera, a reduction of specific probiotics, lactic acid-producing and utilizing bacteria, and an imbalance of anti-inflammatory butyrate-producing bacteria. Substantial heterogeneity across studies concerning demographics and methodologies was also observed. CONCLUSION: This systematic review contribute to a further understanding of the role of gut microbiota in ASD and support the development of microbiota-based diagnostic and therapeutic strategies for ASD.

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19. Wachtel LE, Ghaziuddin N. Dire Need and Disproportionate Access: ECT In Youth With Autism Spectrum Disorders and Other Neurodevelopmental Disorders. J ect;2025 (Jun 2)

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20. Yildirim I, Adak I, Suzer Gamli I, Ekinci O. Methylphenidate-Induced Stuttering in a Patient With Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Case Report. Clin Neuropharmacol;2025 (May 15)

OBJECTIVE: Autism spectrum disorder (ASD) is a common neurodevelopmental condition marked by difficulties in social communication and interaction, along with the presence of repetitive behaviors or interests. ASD often co-occurs with attention deficit hyperactivity disorder (ADHD), and this comorbidity should be considered when developing a treatment plan. Methylphenidate (MPH) is a psychostimulant that is commonly used as the first-line treatment for ADHD. Despite its high effectiveness, adverse effects may occur especially in children with co-occurring ASD. Here, we aimed to present a case with ASD and ADHD who developed stuttering with the onset of MPH and discuss the literature. METHOD AND RESULTS: A 10.5-year-old boy with ASD was referred to our clinic due to symptoms of inattention, hyperactivity, and impulsivity. He was diagnosed with ADHD and prescribed OROS MPH at 18 mg/day, which was increased to 27 mg/day after 1 month. His ADHD symptoms moderately improved, but he began stuttering 1 week after the dosage increase. After discontinuing the medication, his speech fluency significantly improved. Three months later, OROS MPH was reintroduced at 27 mg/day, and the stuttering resumed. Consequently, MPH was discontinued, and his treatment is now being managed with atomoxetine. CONCLUSIONS: Despite that the relationship between MPH and stuttering is not well-documented, it is important to recognize that side effects may arise when initiating treatment or increasing the dosage. Typically, quitting the medication is sufficient to alleviate these side effects. Further studies are needed to better understand the side effects and mechanisms of action associated with MPH.

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21. Zhang E, Zhao T, Sikora T, Ellaway C, Gold WA, Van Bergen NJ, Stroud DA, Christodoulou J, Kaur S. CHD8 Variant and Rett Syndrome: Overlapping Phenotypes, Molecular Convergence, and Expanding the Genetic Spectrum. Hum Mutat;2025;2025:5485987.

Rett syndrome (RTT) is a rare, X-linked, severe neurodevelopmental disorder, predominantly associated with pathogenic variants in the methyl-CpG-binding protein-2 (MECP2) gene, with an increasing number of atypical RTT or RTT-like individuals having pathogenic variants in other genes, such as cyclin-dependent kinase-like 5 (CDKL5) or forkhead box G1 (FOXG1). However, ~20% of individuals with a clinical diagnosis of RTT remain genetically undiagnosed, highlighting the importance of ongoing genomic and functional studies to expand the genetic spectrum of RTT. We present a female who was born to healthy nonconsanguineous parents and presented with severe intellectual disability, macrocephaly, ataxia, absent speech, and poor eye contact. The affected individual was clinically diagnosed with atypical RTT, but genetic testing showed no pathogenic variants in MECP2, CDKL5, or FOXG1. Singleton whole genome sequencing was conducted, which identified a heterozygous stop-gain variant [NM_001170629.2: c.5017C>T, p.(Arg1673⁣(∗))], in the chromodomain-helicase-DNA-binding protein 8 (CHD8) gene. Variant curation revealed its absence in unaffected populations, in silico predictions of pathogenicity, and an existing association with intellectual developmental disorder with autism and macrocephaly (IDDAM) (OMIM #615032). In vitro functional analyses, including Western blots, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and proteomic analyses, demonstrated a significant reduction of the CHD8 transcript and two CHD8 protein isoforms in the proband’s skin fibroblasts relative to control fibroblasts. Additionally, proteomic analysis indicated a significant reduction of the MeCP2 protein, indicating a possible molecular link between CHD8 and MeCP2 and thus clinically between IDDAM and RTT. As the affected individual’s phenotype is consistent with atypical RTT, our results suggest that CHD8 could be considered in the expanding genetic spectrum of atypical RTT, which may assist the diagnosis of other MECP2-negative RTT individuals.

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