1. Berger TD, Fogel Berger C, Gara S, Ben-Zeev B, Weiss B. Nutritional and gastrointestinal manifestations in Rett syndrome: long-term follow-up. Eur J Pediatr. 2024.

PURPOSE: Rett syndrome is a rare neurodevelopmental disorder associated with methyl CpG binding protein 2 (MECP2) gene mutations. We aimed to characterize the long-term nutritional and gastrointestinal course of Rett syndrome in a large national patient population. METHODS: We conducted a retrospective cohort study of patients followed during 1991-2021 at a national center for Rett syndrome. The data retrieved included clinical features, laboratory and genetic analyses. Continuous anthropometric measurements were calculated for the closest visit to the median ages: 2.5, 7.5, 12.5 and 17.5 years. Kaplan Meier curves were used to describe the appearance of clinical manifestations during the follow up period. Generalized estimating equation models were used to compare repeated measurements. RESULTS: Included were 141 patients (139 females), the median age at the first visit was 3.2 years (interquartile range [IQR] 2.3-5.7), and the median length of follow-up was 94.5 months (IQR 28.6-153.3). Mean weight, height and BMI Z-scores were -1.09, -1.03 and -0.56, respectively, at median age 2.5 years; and deteriorated to -3.95, -3.01 and -1.19, respectively, at median age 17.5 years (P < 0.001). Gastrointestinal features included constipation (47.5%, 67/141) and chewing/feeding difficulties (20%, 28/141) at presentation; and an additional 47 (33.3%) and 24 (17.0%), respectively, during follow up. Twenty-eight patients (20%) developed aerophagia and 44 (31.2%) gastroesophageal reflux. No relation was found between genetic mutation types and clinical manifestations. GI manifestations were more prevalent in patients with typical form of Rett syndrome. CONCLUSIONS: Anthropometric parameters were shown to deteriorate with age, regardless of the specific genetic mutation. Chewing/feeding difficulties, constipation and gastroesophageal reflux are common in Rett patients.

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2. Biswas MS, Roy SK, Hasan R, Pk MMU. The crucial role of the cerebellum in autism spectrum disorder: Neuroimaging, neurobiological, and anatomical insights. Health Sci Rep. 2024; 7(7): e2233.

BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by a wide range of symptoms and challenges. While ASD is primarily associated with atypical social and communicative behaviors, increasing research has pointed towards the involvement of various brain regions, including the cerebellum. This review article aims to provide a comprehensive overview of the role of cerebellar lobules in ASD, highlighting recent findings and potential therapeutic implications. METHODS: Using published articles found in PubMed, Scopus, and Google Scholar, we extracted pertinent data to complete this review work. We have searched for terms including anatomical insights, neuroimaging, neurobiological, and autism spectrum disorder. RESULTS: The intricate relationship between the cerebellum and other brain regions linked to ASD has been highlighted by neurobiological research, which has shown abnormalities in neurotransmitter systems and cerebellar circuitry. The relevance of the cerebellum in the pathophysiology of ASD has been further highlighted by anatomical studies that have revealed evidence of cerebellar abnormalities, including changes in volume, morphology, and connectivity. CONCLUSION: Thorough knowledge of the cerebellum’s function in ASD may lead to new understandings of the underlying mechanisms of the condition and make it easier to create interventions and treatments that are more specifically targeted at treating cerebellar dysfunction in ASD patients.

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3. Cardozo LFM, Schwind MR, Pereira APA, Dufner-Almeida LG, Haddad LA, Bruck I, Antoniuk SA. Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil. Arq Neuropsiquiatr. 2024; 82(7): 1-8.

BACKGROUND:  Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE:  To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS:  A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS:  History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION:  The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.

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4. Dickinson A, Ryan D, McNaughton G, Levin A, Naples A, Borland H, Bernier R, Chawarska K, Dawson G, Dziura J, Faja S, Kleinhans N, Sugar C, Senturk D, Shic F, Webb SJ, McPartland JC, Jeste S. Parsing evoked and induced gamma response differences in Autism: A visual evoked potential study. Clin Neurophysiol. 2024; 165: 55-63.

OBJECTIVE: Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism. METHODS: We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6-11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Evoked and induced gamma (30-90 Hz) responses were separately quantified using a wavelet-based time-frequency analysis, and group differences were evaluated using a permutation-based clustering procedure. RESULTS: Autistic children exhibited reduced evoked gamma power but increased induced gamma power compared to TD peers. Group differences in induced responses showed the most prominent effect size and remained statistically significant after excluding outliers. CONCLUSIONS: Our study corroborates recent research indicating diminished evoked gamma responses in children with autism. Additionally, we observed a pronounced increase in induced power. Building upon existing ABC-CT findings, these results highlight the potential to detect variations in gamma-related neural activity, despite the absence of significant group differences in time-domain VEP components. SIGNIFICANCE: The contrasting patterns of decreased evoked and increased induced gamma activity in autistic children suggest that a combination of different EEG metrics may provide a clearer characterization of autism-related circuitry than individual markers alone.

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5. Dudoignon B, Maruani A, Delorme R, Patout M, Fefeu M, Ellul P, Bokov P, Delclaux C. Autism spectrum disorder in young patients with congenital central hypoventilation syndrome: role of the autonomic nervous system dysfunction. Orphanet J Rare Dis. 2024; 19(1): 249.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by alveolar hypoventilation and autonomic nervous system (ANS) dysfunction requiring long-term ventilation. CCHS could constitute a risk factor of autism spectrum disorder (ASD) due to birth injury related to respiratory failure, which remains to be determined. ANS dysfunction has also been described in ASD and there are indications for altered contribution of ANS-central nervous system interaction in processing of social information; thus, CCHS could be a risk factor for ASD based on pathophysiological background also. Our study aimed to determine the prevalence of ASD among CCHS patients, identify risk factors, and explore the relationship between the ANS, evaluated by heart rate variability indices, and adaptative functioning. RESULTS: Our retrospective study, based on the analysis of records of a French national center of patients with CCHS under 20 years of age, determined that the prevalence of ASD (diagnosed by a psychiatrist, following the criteria of DSM-4 or DSM-5) was 6/69 patients, 8.7% (95% confidence interval: 3.3-18.0%). In a case (CCHS with ASD, n = 6) – control (CCHS without ASD, n = 12) study with matching on sex, longer neonatal hospitalization stay and glycemic dysfunction were associated with ASD. Adaptative functioning was assessed using Vineland Adaptative behavioral scales (VABS) and heart rate variability indices (including daytime RMSSD as an index of parasympathetic modulation) were obtained from ECG Holter performed the same day. In 19 young subjects with CCHS who had both ECG Holter and VABS, significant positive correlations were observed between RMSSD and three of four sub-domains of the VABS (communication: R = 0.50, p = 0.028; daily living skills: R = 0.60, p = 0.006; socialization: R = 0.52, p = 0.021). CONCLUSION: Our study suggests a high prevalence of ASD in patients with CCHS. Glycemic dysfunction and longer initial hospitalization stays were associated with ASD development. A defect in parasympathetic modulation was associated with worse adaptative functioning.

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6. Edgar TC, Schlosser R, Koul R. Effects of an Augmentative and Alternative Communication Intervention Package on Socio-Communicative Behaviors Between Minimally Speaking Autistic Children and Their Peers. Am J Speech Lang Pathol. 2024; 33(4): 1619-38.

PURPOSE: The purpose of this study is to investigate the effectiveness of an augmentative and alternative communication (AAC) intervention package consisting of systematic instruction and aided modeling with speech-output technologies on the acquisition, maintenance, and generalization of socio-communicative behaviors-initiating a request for a turn, answering questions, and commenting-in four, minimally speaking (MS) autistic children between the ages of 6 and 9 years. METHOD: A multiple-probe design across behaviors replicated across participants was implemented to evaluate the effects of systematic instruction and aided modeling on initiating requests for a turn, answering questions, and commenting behaviors. Additionally, a pre- and posttreatment multiple-generalization-probes design was used to assess generalization across peers. RESULTS: Visual analyses demonstrated experimental control for two participants (i.e., Derek, Ajay) showing a functional relationship between the intervention and outcomes across all social communicative behavior. For one participant (i.e., Matthew), experimental control could not be established because he did not reach the learning criterion for commenting. The fourth participant (i.e., John) transferred to a different school after making some progress on requesting. Effect size indicator analyses corroborated these findings, indicating medium-to-strong effects for initiating requests for a turn strong effects for answering questions, and medium-to-strong effects for commenting. Generalization of socio-communicative behaviors from researcher to a typically developing peer was variable across participants. Participants maintained socio-communicative behaviors 3 weeks after the last intervention session with varying degrees of success. CONCLUSION: The outcomes of this study suggest that aided modeling and systematic instruction using speech-output technologies may lead to gains in socio-communicative behaviors in some MS autistic children. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25799935.

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7. Ivanova DV, Khabirov RA, Ziganshin AU. Ectonucleotidase Activity in Smooth Muscle Tissues of Rats with a Valproate Model of Autism. Bull Exp Biol Med. 2024.

Ectonucleotidases play an important role in regulating the level of extracellular nucleotides and nucleosides and are an important part of the regulation of the effects of adenosine and ATP on adenosine and P2 receptors, respectively. We have previously established the ambiguous effect of P2 receptor agonists on the contractile activity of smooth muscle tissue in rats with the valproate model of autism. In this work, HPLC was used to evaluate the activity of ectonucleotidases in the smooth muscle tissues of the internal organs of rats with a valproate model of autism. The activity of ectonucleotidases was significantly higher in the smooth muscle tissues of the duodenum, vas deferens, and bladder, but lower in the ileum and uterus. The results obtained make it possible to compare the activity of ectonucleotidases identified here with changes in P2 receptor-mediated contractility of smooth muscle tissues revealed in our previous experiments.

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8. Jan TY, Wong LC, Hsu CJ, Huang CJ, Peng SS, Tseng WI, Lee WT. Developmental change of brain volume in Rett syndrome in Taiwan. J Neurodev Disord. 2024; 16(1): 36.

OBJECTIVE: Rett syndrome (RTT) is characterized by neurological regression. This pioneering study investigated the effect of age on brain volume reduction by analyzing magnetic resonance imaging findings in participants with RTT, ranging from toddlers to adults. METHODS: Functional evaluation and neuroimaging were performed. All scans were acquired using a Siemens Tim Trio 3 T scanner with a 32-channel head coil. RESULTS: The total intracranial volume and cerebral white matter volume significantly increased with age in the control group compared with that in the RTT group (p < 0.05). Cortical gray matter volume reduction in the RTT group continued to increase in bilateral parietal lobes and left occipital lobes (p < 0.05). The differences in cortical gray matter volume between typically developing brain and RTT-affected brain may tend to continuously increase until adulthood in both temporal lobes although not significant after correction for multiple comparison. CONCLUSIONS: A significant reduction in brain volume was observed in the RTT group. Cortical gray matter volume in the RTT group continued to reduce in bilateral parietal lobes and left occipital lobes. These results provide a baseline for future studies on the effect of RTT treatment and related neuroscience research.

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9. Jenabi E, Salehi AM, Ayubi E, Seyedi M, Khazaei S, Jourmand H. Pre and perinatal predictors on autism spectrum disorders: a case-control study in the west of Iran. Matern Health Neonatol Perinatol. 2024; 10(1): 13.

INTRODUCTION: The constellation of pre and perinatal predictors are introduced as predictor for autism spectrum disorders (ASD), however, the information about the direction and strength of these predictors are lacking in Western, Iran. The current study aimed to determine the pre and perinatal predictors of ASD among children in this region. METHODS: This case-control study was conducted in Hamadan, Western Iran during January to March 2022. The study included 100 children with ASD who referred to the autism center as case group. Hundred children without ASD from registration system of health service centers were selected as control group and were matched (1:1) to cases by age and place of residency. A structured questionnaire about pre and perinatal predictors of ASD was developed by an expert panel. The questionnaire was administered by interviewing the mothers of children. RESULTS: Boy gender (OR: 3.51, 95% CI: 1.74-7.10, p-value < 0.001), small for gestational age (SGA) (3.92, 1.64-9.39, 0.002), maternal diabetes (3.51, 1.03-24.95, 0.04) and family history of mental disorders (3.64, 1.18-11.27, 0.04) were identified as significant predictors in a multivariable analysis. CONCLUSION: Our study emphasizes on the importance of screening and monitoring for ASD in the boys, those with history of SGA, from mothers with history of diabetes and with family history of mental disorders. Proposing the replication of findings emphasizes the necessity of conducting studies with larger sample sizes.

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10. Karimi Z, Zarifkar A, Mirzaei E, Dianatpour M, Dara M, Aligholi H. Therapeutic effects of nanosilibinin in valproic acid-zebrafish model of autism spectrum disorder: Focusing on Wnt signaling pathway and autism spectrum disorder-related cytokines. Int J Dev Neurosci. 2024.

In this study, we delved into the intricate world of autism spectrum disorder (ASD) and its connection to the disturbance in the Wnt signaling pathway and immunological abnormalities. Our aim was to evaluate the impact of silibinin, a remarkable modulator of both the Wnt signaling pathway and the immune system, on the neurobehavioral and molecular patterns observed in a zebrafish model of ASD induced by valproic acid (VPA). Because silibinin is a hydrophobic molecule and highly insoluble in water, it was used in the form of silibinin nanoparticles (nanosilibinin, NS). After assessing survival, hatching rate, and morphology of zebrafish larvae exposed to different concentrations of NS, the appropriate concentrations were chosen. Then, zebrafish embryos were exposed to VPA (1 μM) and NS (100 and 200 μM) at the same time for 120 h. Next, anxiety and inattentive behaviors and the expression of CHD8, CTNNB, GSK3beta, LRP6, TNFalpha, IL1beta, and BDNF genes were assessed 7 days post fertilization. The results indicated that higher concentrations of NS had adverse effects on survival, hatching, and morphological development. The concentrations of 100 and 200 μM of NS could ameliorate the anxiety-like behavior and learning deficit and decrease ASD-related cytokines (IL1beta and TNFalpha) in VPA-treated larvae. In addition, only 100 μM of NS prevented raising the gene expression of Wnt signaling-related factors (CHD8, CTNNB, GSK3beta, and LRP6). In conclusion, NS treatment for the first 120 h showed therapeutic effect on an autism-like phenotype probably via reducing the expression of pro-inflammatory cytokines genes and changing the expression of Wnt signaling components genes.

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11. Kissel LT, Pochareddy S, An JY, Sestan N, Sanders SJ, Wang X, Werling DM. Sex-Differential Gene Expression in Developing Human Cortex and Its Intersection With Autism Risk Pathways. Biol Psychiatry Glob Open Sci. 2024; 4(4): 100321.

BACKGROUND: Sex-differential biology may contribute to the consistently male-biased prevalence of autism spectrum disorder (ASD). Gene expression differences between males and females in the brain can indicate possible molecular and cellular mechanisms involved, although transcriptomic sex differences during human prenatal cortical development have been incompletely characterized, primarily due to small sample sizes. METHODS: We performed a meta-analysis of sex-differential expression and co-expression network analysis in 2 independent bulk RNA sequencing datasets generated from cortex of 273 prenatal donors without known neuropsychiatric disorders. To assess the intersection between neurotypical sex differences and neuropsychiatric disorder biology, we tested for enrichment of ASD-associated risk genes and expression changes, neuropsychiatric disorder risk genes, and cell type markers within identified sex-differentially expressed genes (sex-DEGs) and sex-differential co-expression modules. RESULTS: We identified 101 significant sex-DEGs, including Y-chromosome genes, genes impacted by X-chromosome inactivation, and autosomal genes. Known ASD risk genes, implicated by either common or rare variants, did not preferentially overlap with sex-DEGs. We identified 1 male-specific co-expression module enriched for immune signaling that is unique to 1 input dataset. CONCLUSIONS: Sex-differential gene expression is limited in prenatal human cortex tissue, although meta-analysis of large datasets allows for the identification of sex-DEGs, including autosomal genes that encode proteins involved in neural development. Lack of sex-DEG overlap with ASD risk genes in the prenatal cortex suggests that sex-differential modulation of ASD symptoms may occur in other brain regions, at other developmental stages, or in specific cell types, or may involve mechanisms that act downstream from mutation-carrying genes. Males are more commonly diagnosed with autism spectrum disorder than females, and sex differences in brain development may contribute to this difference. Here, we define differences in gene expression patterns between males and females in human prenatal brain tissue from 273 donors to identify 101 genes that are expressed at different levels in males and females and gene sets that show sex-specific expression correlations. Genes with autism-associated DNA variants and genes with altered expression in autism do not preferentially overlap with sex-differential genes, suggesting that sex-differential biology may influence autism risk mechanisms in other brain regions, at other developmental stages, or in specific cell types. eng.

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12. Knight EJ, Altschuler TS, Molholm S, Murphy JW, Freedman EG, Foxe JJ. It’s all in the timing: Delayed feedback in autism may weaken predictive mechanisms during contour integration. J Neurophysiol. 2024.

Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through conveyance of statistical predictions based on prior exposure to stimulus configurations. Individuals with autism spectrum disorder (ASD) show biases in stimulus processing toward parts rather than wholes, suggesting their sensory processing may be less shaped by statistical predictions acquired through prior exposure to global stimulus properties. Investigations of illusory contour (IC) processing in neurotypical (NT) adults have established a well-tested marker of contour integration characterized by a robust modulation of the visually evoked potential (VEP) – the IC-effect – that occurs over lateral occipital scalp during the timeframe of the N1 component. Converging evidence strongly supports the notion that this IC-effect indexes a signal with significant feedback contributions. Using high-density VEPs, we compared the IC-effect in 6-7-year-old children with ASD (n=32) or NT development (n=53). Both groups of children generated an IC-effect that was equivalent in amplitude. However, the IC-effect notably onset 21ms later in ASD, even though initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared to NT children. This delay in the feedback dependent IC-effect, in the context of known developmental differences between feedforward and feedback fibers, suggests a potential pathophysiological mechanism of visual processing in ASD, whereby ongoing stimulus processing is less shaped by statistical prediction mechanisms.

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13. Lai CC, Hsieh HC, Lee WK, Lin CH, Lin HY. Application of remodeled glove puppetry for children with developmental disabilities: A randomized controlled trial. Assist Technol. 2024; 36(4): 256-63.

This study aimed to improve hand performance and play behavior in children with developmental disabilities (DD) using a remodeled glove puppetry approach. Overall, 62 children with DD were randomly assigned to experimental and control groups (n = 31 each). The experimental group underwent a 12-week rehabilitation program by playing with the remodeled glove puppetry, while the children in the control group played with non-remodeled glove puppetry. The Chinese puppet was remodeled using a Lego EV3® robot. Hand kinematics were analyzed through the Siliconcoach® Pro 7 software, which measured the force produced by the baseline ® hydraulic pinch gauge. Play behavior was measured using the Knox Preschool Play Scale-revised (KPPS-r). The experimental group exhibited significant improvements compared to the control group in hand kinematics (wrist range of motion [ROM], p < .05; metacarpophalangeal ROM, p < .05; proximal interphalangeal ROM, p < .05) and KPPS-r scores (space management, p < .05; material management, p < .05; pretense-symbolic, p < .05; participation, p < .05). After the 12-week rehabilitation with the remodeled glove puppetry, the experimental group exhibited significant improvement in kinematics and KPPS-r scores.

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14. Lam BYH, Wong CSM, Cheung VKW, Wong SMY, Lui SSY, Chan KT, Wong MTH, Chan SKW, Lee EHM, Chang WC, Wong GHY, Hui CLM, Chen EYH. Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong. East Asian Arch Psychiatry. 2024; 34(2): 23-8.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

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15. Le Bras A. Sensory perception deficits in ASD mouse models. Lab Anim (NY). 2024; 53(7): 175.

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16. Parvan M, Nozari M, Shabani M, Nozari H, Kohlmeier KA, Mohammadi S. Effects of agmatine on radial-arm maze memory performance and autistic-like behaviors in a male rat model of autism. Birth Defects Res. 2024; 116(7): e2379.

BACKGROUND: Autism spectrum disorder (ASD) is the fastest-growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic-like behaviors were assessed. METHODS: Autism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism-associated behaviors in male offspring were examined in an open field test (OFT) and three-chambered test (TCT) on postnatal days 50-51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty-eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT. RESULTS: VPA-treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety-like behavior induced by VPA without the effect on RAM. CONCLUSION: In a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety-like behavior in autistic animals.

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17. Shaughnessy N, Herbert R, Williams E, Walduck J, von Jungenfeld R, Newman H. Playing with data differently: engaging with autism and gender through participatory arts/music and a performative framework for analysis. Front Psychol. 2024; 15: 1324036.

There are increasing demands for Participatory Arts-Based (PAB) programs involved in health research to better evidence outcomes using robust quantitative evaluation methodologies taken from science, such as standardized questionnaires, to inform commissioning and scale-up decisions. However, for PAB researchers trying to do this, barriers arise from fundamental interdisciplinary differences in values and contexts. Researchers are required to navigate the tensions between the practice-based evidence produced by the arts and the evidence-based practice sought by psychologists. Consequently, there is a need for interdisciplinary arts-science collaborations to produce alternative methods of evaluation that are better aligned to PAB approaches, and which combine systematic rigor with a sensitivity to the values, contexts and strengths of this approach. The current article centers on the development of an alternative transdisciplinary analytic tool, the Participatory arts Play Framework (PP-Framework), undertaken as part of an arts-psychology collaboration for a UK AHRC-funded PAB research project: Playing A/Part: Investigating the identities and experiences of autistic girls. We present details of three stages in the development of the PP-Framework: 1. preliminary emergence of the framework from initial video analysis of observational data from participatory music and sound workshops run for 6 adolescent autistic girls (aged 11-16); 2. identification and application of modes of engagement; and 3. further testing of the framework as an evaluation tool for use in a real-world setting, involving professional musicians engaged in delivery of a creative music project at a center for homeless people. The PP-Framework maps types of participation in terms of performative behaviors and qualities of experience, understood as modes of play. It functions as a vehicle for analyzing participant engagement, providing a tool predicated on the processes of working in creative participatory contexts while also being sensitive to the esthetic qualities of what is produced and capable of capturing beneficial changes in engagement. It offers a conceptual approach for researchers to undertake observation of participatory arts practices, taking account of embodied engagement and interaction processes. It is informed by understandings of autistic performativity and masking in conjunction with an ecological understanding of sense making as being shaped by environments, social relations and sensing subjectivity. The framework has the potential to be a bi-directional tool, with application for both practitioners and participants.

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18. Weiss MD, Daniolos PT, Coughlin K, Mulvaney-Day N, Cook B, Rosenblum D. A Scoping Review of the Intersectionality of Autism and Intellectual and Developmental Disability with Social Inequity on Diagnosis and Treatment of Youth. J Child Adolesc Psychopharmacol. 2024.

Objective: To describe how the intersectionality of race, ethnicity, and language with autism and intellectual and developmental disability (IDD) impacts mental health inequities in psychopharmacological management of youth. Method: This was a scoping review in which a series of searches were conducted in PubMed, Web of Science, Google Scholar, and manual review of the articles collected. Results: Although autism and/or IDD increases the risk for poor physical and mental health, social determinants of health such as race, ethnicity, and language account for approximately a third of poor outcomes. Minoritized children with autism/IDD experience significantly greater delays to diagnosis and misdiagnosis and are less likely to receive appropriate services. Access to psychological testing and psychosocial services is often limited by availability, skilled practitioners, a shortage of non-English-language providers or interpreters, and poor reimbursement. Conclusion: The intersectionality of autism and/or IDD with race, ethnicity, and language compounds the health inequities associated with either of these challenges independently.

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19. Wright JR, Astrovskaya I, Barns SD, Goler A, Zhou X, Shu C, Snyder LG, Han B, Shen Y, Volfovsky N, Hall JB, Feliciano P, Chung WK. Return of genetic research results in 21,532 individuals with autism. Genet Med. 2024: 101202.

PURPOSE: The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings. METHODS: We present results from microarray genotyping and exome sequencing (ES) of 21,532 individuals with autism and 17,785 of their parents. We returned LP and P (American College of Medical genetics (ACMG) criteria) copy number variants (CNVs), chromosomal aneuploidies, and variants in genes with strong evidence of association with autism and intellectual disability. RESULTS: We identified 1903 ‘returnable’ LP/P variants in 1861 individuals with autism (8.6%). 89.5% of these variants were not known to participants. The diagnostic genetic result was returned to 589 participants (53% of those contacted). Features associated with a higher probability of having a returnable result include cognitive and medically complex features, being female, being White (versus non-White) and being diagnosed more than 20 years ago. We also find results among autistics across the spectrum, as well as in transmitting parents with neuropsychiatric features but no autism diagnosis. CONCLUSION: SPARK offers an opportunity to assess returnable results among autistic people who have not been ascertained clinically. SPARK also provides practical experience returning genetic results for a behavioral condition at a large scale.

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20. Yang F, Wang M. Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay. BMC Med Genomics. 2024; 17(1): 175.

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient’s mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene’s mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.

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21. Yuan YX, Liu Y, Zhang J, Bing YH, Chen CY, Li GG, Chu CP, Yin MJ, Qiu DL. Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice. Transl Psychiatry. 2024; 14(1): 272.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

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