1. Elise F, Irvine B, Brinkert J, Hamilton C, Farran EK, Milne E, Scerif G, Remington A. Perceptual Experiences of Autistic People With an Intellectual Disability and People With Williams Syndrome: A Reflexive Thematic Analysis. J Appl Res Intellect Disabil. 2025; 38(1): e13326.

BACKGROUND: Autistic people without intellectual disabilities have increased perceptual capacity: they can process more information at any given time compared to non-autistic people. We examined whether increased perceptual capacity is evident across the autistic spectrum (i.e. for autistic people with intellectual disabilities) and whether it is specific to autism, or also experienced by people with Williams Syndrome (WS). METHODS: Five autistic adults with intellectual disabilities and five adults with WS took part in accessible, qualitative interviews. Responses were analysed using thematic analysis. RESULTS: Both groups expressed enjoyment of focussed attention, with autistic participants preferring multiple simultaneous inputs. Responses suggested increased perceptual capacity for autistic participants only. The sensory environment was reported to be anxiety-inducing for both groups. CONCLUSIONS: This study gives preliminary evidence that increased perceptual capacity may be universal across the autistic spectrum, and specific to autism. Understanding differences in capacity offers more targeted suggestions to support sensory challenges.

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2. Endo N, Hiraishi A, Goto S, Nozu H, Mannari-Sasagawa T, Horii-Hayashi N, Kitsuki M, Okuda M, Makinodan M, Nishi M. Dysregulated HPA axis during postnatal developmental stages in the BTBR T(+) Itpr3(tf)/J mouse: A model of autism spectrum disorder. Neuropsychopharmacol Rep. 2024.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T(+) Itpr3(tf)/J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning.

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3. Furukawa S, Kushima I, Kato H, Kimura H, Nawa Y, Aleksic B, Banno M, Yamamoto M, Uematsu M, Nagasaki Y, Ogi T, Ozaki N, Ikeda M. Whole-genome sequencing analysis of Japanese autism spectrum disorder trios. Psychiatry Clin Neurosci. 2024.

AIM: Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous neurodevelopmental disorder with a strong genetic basis. Conducting the first comprehensive whole-genome sequencing (WGS) analysis of Japanese ASD trios, this study aimed to elucidate the clinical significance of pathogenic variants and enhance the understanding of ASD pathogenesis. METHODS: WGS was performed on 57 Japanese patients with ASD and their parents, investigating variants ranging from single-nucleotide variants to structural variants (SVs), short tandem repeats (STRs), mitochondrial variants, and polygenic risk score (PRS). RESULTS: Potentially pathogenic variants that could explain observed phenotypes were identified in 18 patients (31.6%) overall and in 10 of 23 patients (43.5%) with comorbid intellectual developmental disorder (IDD). De novo variants in PTEN, CHD7, and HNRNPH2 were identified in patients referred for genetic counseling who exhibited previously reported phenotypes, including one patient with ASD who had profound IDD and macrocephaly with PTEN L320S. Analysis of the AlphaFold3 protein structure indicated potential inhibition of intramolecular interactions within PTEN. SV analysis identified deletions in ARHGAP11B and TMLHE. A pathogenic de novo mitochondrial variant was identified in a patient with ASD who had a history of encephalitis and cognitive decline. GO enrichment analysis of genes with nonsense variants and missense variants (Missense badness, PolyPhen-2, and Constraint >1) showed associations with regulation of growth and ATP-dependent chromatin remodeler activity. No reportable results were obtained in the analysis of STR and PRS. CONCLUSION: Characterizing the comprehensive genetic architecture and phenotypes of ASD is a fundamental step towards unraveling its complex biology.

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4. Gordon K, Susko M, de la Roche L, Kelley E. Experiences of Affiliate Stigma and Depressive Symptoms in Caregivers of Autistic Children: The Moderating Effect of Social Support. J Autism Dev Disord. 2024.

Caregivers with an autistic child often experience stigma, which can lead to detrimental mental health consequences. Affiliate stigma is the internalization of, and psychological responses to, stigma experienced due to an individual’s association with a person who is stigmatized. Social support has been shown to mediate the relationship between affiliate stigma and depression in caregivers of special needs children. However, research on social support as a moderator of this relationship in autistic children has not been completed. We examined the associations between affiliate stigma, social support, and depression as well as the moderating role of social support. Using online questionnaires, 110 caregivers of autistic children reported their child’s autistic traits, affiliate stigma, perceived social support and depressive symptoms. A moderated regression was run to determine if social support significantly impacted the association between affiliate stigma and depression. Affiliate stigma was positively associated with depressive symptoms and social support was negatively associated with depressive symptoms. The moderating effect of social support on the relationship between affiliate stigma and depressive symptoms was not significant. Upon separating the social support variable into family, significant other, and friend subgroups, no additional significant moderators were found. This is one of the first studies to investigate affiliate stigma in North America and demonstrates that affiliate stigma is not only experienced by parents of autistic children but is significantly associated with depression. Clinicians working with these parents might focus on overcoming affiliate stigma to potentially ameliorate their client’s depression.

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5. Hill MM, Gangi DN, Miller M. Toddler Screen Time: Longitudinal Associations with Autism and ADHD Symptoms and Developmental Outcomes. Child Psychiatry Hum Dev. 2024.

Greater screen time is associated with increased symptoms of autism spectrum disorder (autism), attention-deficit/hyperactivity disorder (ADHD), and lower scores on measures of development in preschool-aged community samples. In the current longitudinal study, we examined screen time differences at 18 months of age based on clinically-defined outcomes (i.e., Autism, ADHD Concerns, Comparison) determined at age 3-5 years in a genetically-enriched sample based on family history, along with prospective associations between toddler screen time and preschool autism/ADHD symptoms and developmental achievement. Participants (n = 82) included children at high and low familial likelihood for autism and ADHD. Children with Autism and ADHD Concerns outcomes experienced significantly more screen exposure at 18 months than children without autism or elevated symptoms of ADHD. Greater screen time at 18 months was also associated with preschool symptoms of autism and ADHD and lower developmental achievement across the sample. Preschoolers with neurodevelopmental challenges experienced more screen exposure earlier in development than same-age peers, increasing potential for negative developmental impacts.

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6. Rojas V, Carrasco-Gallardo C, Tenorio L, Olesen MA, Tapia V, Carrasco M, Araos P, Quintanilla RA, Ruiz LM. Analysis of mitochondrial DNA replisome in autism spectrum disorder: Exploring the role of replisome genes. Autism Res. 2024.

Autism spectrum disorder (ASD) is a neurodevelopmental condition often associated with mitochondrial dysfunction, including increased mitochondrial DNA (mtDNA) copy number and impaired energy production. This study investigates the role of the mitochondrial replisome-specifically, the genes TFAM, TWNK, POLG, and TOP1MT-in mtDNA replication and its potential contribution to ASD pathophysiology. We analyzed samples from the oral mucosa of children with ASD and typically developing (TD) controls, assessing mtDNA copy number, gene expression, and protein levels. Our findings revealed a significant increase in mtDNA copy number in the oral mucosa of ASD children, along with partially deleted mtDNA molecules. However, there were no significant changes in the expression of TFAM, TWNK, POLG, or MT-TL1 genes between ASD and TD samples. Additionally, TFAM protein levels, including monomeric, dimeric, and trimeric forms, did not differ significantly. We also observed increased oxidative stress and inflammatory markers in the oral mucosa of ASD children, suggesting that mitochondrial alterations may be linked to inflammation and oxidative damage in ASD. To further investigate the functional impact of TFAM, we overexpressed it in human HEK293 cells and cortical neurons (CN1.4). TFAM overexpression led to increased mtDNA copy number, cell proliferation, and ATP production in HEK293 cells, but did not significantly alter mitochondrial gene expression, protein oxidation, or mtDNA integrity. In CN1.4 neurons, TFAM overexpression increased mitochondrial membrane potential and length, indicating potential changes in mitochondrial dynamics. Overall, our study suggests that while mtDNA alterations are present in ASD, they are not directly driven by changes in mitochondrial replisome gene expression. These findings highlight the complexity of mitochondrial dysfunction in ASD and suggest the need for further investigation into the underlying molecular mechanisms.

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7. Su WC, Srinivasan S, Bhat AN. Effects of Creative Movement, General Movement, or Seated Play Interventions on Motor Performance in Children with Autism Spectrum Disorder: A Pilot Randomized Controlled Trial. Res Autism Spectr Disord. 2025; 119.

BACKGROUND: Children with ASD experience significant gross motor challenges that could be addressed using motor interventions. However, contemporary ASD interventions that are sedentary in nature often target communication and fine motor skills and not children’s gross motor difficulties. METHODS: In the current pilot RCT, we evaluated changes in various motor outcomes (i.e., gross/fine motor coordination, locomotor skills, functional endurance, and praxis/imitation performance) following two types of whole-body motor interventions (Creative Movement (CM) or General Movement (GM)) and compared them to a Sedentary Play (SP) intervention focused on improving fine motor skills in children with ASD. Forty-five children with ASD (Mean Age ±SE: 8.7 ± 0.3, 38 males) were randomly assigned to the CM, GM, or SP groups and received 8 weeks of group-specific training. RESULTS: Both CM and GM interventions led to medium-to-large improvements in gross motor performance, including improved body coordination, strength/agility, locomotor skills, and walking endurance. Children in the CM group additionally showed medium-to-large-sized improvements in praxis performance, while children in the SP group showed improvements in fine motor performance. These training-related improvements were supported by improvements reported via parental questionnaires. CONCLUSIONS: Researchers and clinicians should incorporate whole-body interventions targeting gross motor skills in the plan of care for children with ASD.

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8. Thomas BR, Ludwig NN, Pelletier D, Bauer M, Hommer R, Smith-Hicks C, O’Connor JT. Cortical Vision Impairment (CVI)-informed assessment and treatment of challenging behavior in a child with SCN2A-related disorder. J Neurodev Disord. 2024; 16(1): 66.

This report presents results of parent-implemented behavioral treatments for a child with cortical visual impairment (CVI), intellectual disability (ID), epilepsy, and autism spectrum disorder (ASD) associated with a pathogenic variant in the SCN2A gene (i.e., SCN2A-Related Disorder). Treatment evaluations were informed by combined results of functional behavior assessment (FBA) and functional vision assessment (FVA) which yielded CVI-related accommodations. The treatment of escape-maintained challenging behavior involved the evaluation of behavioral prompting strategies in accordance with CVI-related accommodations, extinction (EXT), and differential reinforcement modifications. The treatment for behavior problems maintained by access to food (tangible-edible) included functional communication training (FCT), EXT, and schedule thinning with schedule-correlated visual signals. Overall, integrating child-specific CVI-related accommodations was essential for developing effective behavioral interventions for this child. FVAs are accessible and practical for uptake by behavior analysts in vision-informed assessment and treatment of challenging behavior.

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9. To JCS, Hui MMC, Kung KTF. Self-Reported Multidimensional Gender Identity in Autistic and Non-Autistic Children. J Autism Dev Disord. 2024.

ABSRACT: PURPOSE: The several prior studies assessing gender identity in young autistic individuals mostly included a mix of child and adolescent participants, heavily relied on parent-reported measures, and yielded mixed findings. A single parent-reported item from the Child Behavior Checklist assessing « wish to be of the opposite sex » was employed in most of these studies. Only one prior study focused specifically on children, but that study employed parent-reported measures. METHODS: Using self-reported multidimensional measures, the present study assessed gender identity in autistic and non-autistic children aged 4 to 11 years (30 autistic boys, 35 non-autistic boys, 20 autistic girls, 35 non-autistic girls). Child-friendly measures were used to assess own-gender similarity, other-gender similarity, gender contentedness, and wish to be of the other gender. Vocabulary and non-verbal reasoning were also assessed. RESULTS: Based on descriptive statistics, compared with non-autistic boys, autistic boys showed increased gender identity variance across all four dimensions (lower own-gender similarity, higher other-gender similarity, lower gender contentedness, greater wish to be of the other gender). These group differences between autistic and non-autistic boys were medium and statistically significant for three of the four dimensions and small-to-medium and marginally significant for the remaining dimension. Autistic girls and non-autistic girls did not show consistent or significant differences in gender identity. There were no differences between the autistic and non-autistic groups in vocabulary or non-verbal reasoning in either boys or girls. CONCLUSION: Gender identity variance may emerge early in development in autistic individuals, but the trajectory may differ for boys and girls.

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10. Wieting J, Jahn K, Bleich S, Deest M, Frieling H. Sex differences in MAGEL2 gene promoter methylation in high functioning autism – trends from a pilot study using nanopore Cas9 targeted long read sequencing. BMC Med Genomics. 2024; 17(1): 279.

BACKGROUND: MAGEL2 is an autism susceptibility gene whose deficiency has been associated with autism-related behaviors in animal models and in syndromic human autism spectrum disorders (ASDs) such as Schaaf-Yang syndrome, but has not been studied in the broader autism spectrum. Given the capabilities of long-read sequencing technologies, this pilot study used a targeted nanopore sequencing approach to simultaneously examine MAGEL2 DNA sequence and methylation in adults with high-functioning autism (HFA) compared to neurotypical controls (NC). METHODS: Using DNA extracted from peripheral blood, Cas9-targeted nanopore DNA sequencing was used to analyze MAGEL2, including its entire regulatory construct (chr15:23639316-23651466), for sequence variation and 5-methyl-cytosine (5mC) modification in a cohort of adults with HFA compared to sex- and age-matched NC. Given the known sex differences in ASD and MAGEL2 KO animal models, results were further analyzed by sex. RESULTS: 20 adults with HFA (10 males, 10 females) and 20 NC were included. While there were no overall differences in MAGEL2 DNA sequence and 5mC modification between HFA and NC, we found a significant difference in MAGEL2 gene promoter methylation between males and females with HFA and NC of both sexes, with HFA males tending to show hypomethylation in a 300 bp long differentially methylated region (chr15:23647640-23647939) around the MAGEL2 transcription start site. CONCLUSIONS: In this pilot study utilizing nanopore Cas9 targeted DNA sequencing, significant sex-specific differences in MAGEL2 gene promoter methylation were identified in male adults with HFA in comparison to control groups, suggesting the potential for sex-specific epigenetic differences. However, further replication in larger cohorts is required to validate these findings.

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11. Wong PCM, Hirai HW, Wang L, Qi X, Poon ECH, Chan MSM, Yeung GTY, Lai ECL, To CKS. Parent coaching to target language outcomes for Chinese-learning autistic preschoolers: A preliminary study. J Commun Disord. 2024; 113: 106477.

PURPOSE: The present study evaluates the preliminary effectiveness of a parent-implemented support program to enhance language outcomes in Chinese-learning preschoolers with a confirmed diagnosis or at elevated likelihood of autism, a lifelong neurodevelopmental condition. The program is delivered entirely online with the option of a group format. Because of cross-cultural differences in adult learning and parent-child interaction and because parent coaching programs for autism that are delivered online are only emerging, a specific study to evaluate the effectiveness of online support for Chinese families is warranted. METHODS: A case control study with 22 families, 12 families in the Active support group and 10 in the Control group, was conducted. Families in the Active group attended 20 online lessons across 6 months in which they learned seven communication strategies to be implemented with their child at home. Extensive coaching and video feedback were provided. Before and after the online support, a 5 min parent-child interaction video collected at home via videoconferencing was used to code for mean length of utterances, type and token frequencies and percentage of pronoun production. RESULTS: As revealed by the Wilcoxon Signed rank tests, the Active group showed significant support-related improvement on all language measures except for type token ratio, with effect sizes in at least the moderate range. The Control group did not show statistically reliable support-related changes. CONCLUSIONS: Parent coaching delivered in an online mode and with the option of a group format is potentially effective in enhancing language outcomes for Chinese-learning autistic children. A larger-scale study based on these preliminary findings should be conducted.

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12. Zhang F, Liu L, Peng J, Ding G, Li Y, Biswal BB, Wang P. Transdiagnostic and Diagnosis-Specific Morphological Similarity Related Transcriptional Profile in Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2024.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both highly heritable developmental psychiatric disorders and exhibit a high degree of comorbidity. Our objective is to enhance understanding of the transdiagnostic and diagnosis-specific structural alterations and related cellular and genetic pathophysiological mechanisms between ADHD and ASD. METHOD: We used structural magnetic resonance imaging data of 247 subjects from the publicly available 1000 Functional Connectomes Project, including 91 individuals with ADHD, 49 individuals with ASD, and 107 age- and sex-matched controls. We performed morphological similarity networks (MSN) and gene transcriptional profile analysis on these image data to identify the anatomic changes and MSN-related genes. Enrichment analysis was further conducted on ADHD/ASD risk genes and MSN-related genes. RESULTS: Individuals with ADHD showed the diagnosis-specific MSN changes distributing in areas related to high-level cognitive functions, while ASD had MSN changes in areas related to language comprehension and spatial location. ADHD and ASD exhibited the transdiagnostic morphological increase in the right middle temporal gyrus. Gene transcriptional profile analysis showed enrichment of ADHD and ASD risk genes in more than ten biological processes, primary including function of synapse transmission and development. Genes in excitatory and inhibitory neurons also enriched in pathways with similar function. CONCLUSION: The transdiagnostic morphological dedifferentiation in the right middle temporal gyrus might indicate the shared motion impairments in ADHD and ASD. The evidence from the transcription of MSN-related genes further indicate a potential imbalance in excitatory and inhibitory neural pathways in ADHD and ASD. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex balance in the selection of non-human subjects. We worked to ensure diversity in experimental samples through the selection of the cell lines. We worked to ensure diversity in experimental samples through the selection of the genomic datasets. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

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