1. Almeida AFS, Silva TDD, Moraes Í AP, Menezes LDC, Dias ED, Araújo LV, Monteiro CBM, Dawes H, Simcsik AO, Alberissi CAO, Silva V, Brunherotti MAA, Tonello MGM. Virtual reality as a telerehabilitation strategy for people with autism spectrum disorder during the COVID-19 quarantine scenario: physical activity, motor performance and enjoyment. Disability and rehabilitation Assistive technology. 2023: 1-11.

PURPOSE: People with autism spectrum disorder could benefit from physical activity during the pandemic and COVID-19 restrictions, mainly to maintain adequate physical activity. We aimed to evaluate the feasibility, enjoyment, and potential effect of telerehabilitation using a serious game named ‘MoveHero’. MATERIALS AND METHODS: Registered in Clinical Trials (NCT04402034). We adopted a remotely run Telerehabilitation research design with 44 participants recruited: 22 People with ASD people and 22 non-ASD individuals. RESULTS: All participants safely participated, 100% adherence to sessions, ∼60% enjoying the task, and significantly improved performance, with better performance for the NA group at most practice moments. CONCLUSIONS: Our findings support both how to implement a gaming intervention and the need to investigate the efficacy of serious games to motivate moderate intensity physical activity in people with ASD. A new and thrilling way to promote physical activity is through telerehabilitation to people with Autism Spectrum Disorder.A tool that can possibly influence the mood of people with Autism Spectrum Disorder.Help to implement home-based rehabilitation to people with Autism Spectrum Disorder. eng.

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2. Arthur T, Vine S, Buckingham G, Brosnan M, Wilson M, Harris D. Testing predictive coding theories of autism spectrum disorder using models of active inference. PLoS computational biology. 2023; 19(9): e1011473.

Several competing neuro-computational theories of autism have emerged from predictive coding models of the brain. To disentangle their subtly different predictions about the nature of atypicalities in autistic perception, we performed computational modelling of two sensorimotor tasks: the predictive use of manual gripping forces during object lifting and anticipatory eye movements during a naturalistic interception task. In contrast to some accounts, we found no evidence of chronic atypicalities in the use of priors or weighting of sensory information during object lifting. Differences in prior beliefs, rates of belief updating, and the precision weighting of prediction errors were, however, observed for anticipatory eye movements. Most notably, we observed autism-related difficulties in flexibly adapting learning rates in response to environmental change (i.e., volatility). These findings suggest that atypical encoding of precision and context-sensitive adjustments provide a better explanation of autistic perception than generic attenuation of priors or persistently high precision prediction errors. Our results did not, however, support previous suggestions that autistic people perceive their environment to be persistently volatile.

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3. Cheng SL, Cheng S, Liu S, Li Y. What happened to parents’ views of school success for autistic children during the COVID-19 pandemic?. Frontiers in psychiatry. 2023; 14: 1211041.

BACKGROUND: The educational views of parents with autistic children directly impacts their children’s academic success. However, little research has been done on how the COVID-19 pandemic impacted parents’ academic and social views. AIM: This study analyzes parents’ views of school success for their autistic children in the context of the COVID-19 pandemic and examines the relationships among pandemic stress, parental involvement, and parents’ views of school success for autistic children in mainland China. METHODS: In this study, 713 parents of autistic children completed measures assessing their pandemic stress, parental involvement, and views of school success; linear regression and structural equation modeling were used to analyze the data. RESULTS: Parents’ views of school success were influenced by factors such as parents’ level of education, household income, parents’ gender, and children’s age. The effects of pandemic stress on views of school success for parents of autistic children are complex: physical and mental reaction has a negative direct effect on views of school success, a positive indirect effect mediated by parental involvement, and a net positive effect; risk perception and concern has a negative indirect effect; and both the direct and indirect effects of pragmatic hopefulness are positive. Education policymakers and practitioners need to seriously and carefully assess these results’ implications for modern, inclusive education.

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4. Clarke KA, Siegel M, Williams DL. The Relationship Between Augmentative and Alternative Communication Use by Pediatric Psychiatric Inpatients With Autism Spectrum Disorder and Interfering Behaviors. American journal of speech-language pathology. 2023; 32(5): 2040-56.

PURPOSE: Previous research conducted by Williams et al. (2018) using data from the Autism Inpatient Collection (AIC) found a weak and inconsistent association between verbal ability and the severity of interfering behaviors; however, adapting/coping scores were significantly associated with self-injury, stereotypy, and irritability (including aggression and tantrums). The previous study did not account for access to or use of alternative forms of communication in their sample population. This study uses retrospective data to investigate the association between verbal ability and augmentative and alternative communication (AAC) use and the presence of interfering behaviors in individuals with autism who have complex behavioral profiles. METHOD: The sample included 260 autistic inpatients, ages 4-20 years, from six psychiatric facilities, enrolled during the second phase of the AIC when detailed information about AAC use was collected. Measures included AAC use, method, and function; comprehension and production of language; receptive vocabulary; nonverbal IQ; severity of interfering behaviors; and the presence and severity of repetitive behaviors. RESULTS: Lower language/communication abilities were related to increased repetitive behaviors and stereotypies. More specifically, these interfering behaviors appeared to be related to communication in those individuals who were candidates for AAC but who were not reported to have access to it. Although the use of AAC did not predict a decrease in interfering behaviors, receptive vocabulary scores-as measured by the Peabody Picture Vocabulary Test-Fourth Edition-were positively correlated with the presence of interfering behaviors in participants with the most complex communication needs. CONCLUSIONS: The communication needs of some individuals with autism may be unmet, prompting the use of interfering behaviors as a form of communication. Further investigation of the functions of interfering behaviors and the related functions of communication skills may provide greater support for an increased focus on the provision of AAC to prevent and ameliorate interfering behaviors in individuals with autism.

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5. Fass SB, Mulvey B, Yang W, Selmanovic D, Chaturvedi S, Tycksen E, Weiss LA, Dougherty JD. Relationship between sex biases in gene expression and sex biases in autism and Alzheimer’s disease. medRxiv : the preprint server for health sciences. 2023.

Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-seq datasets using both within-region and pan-regional frameworks. We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-cell data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer’s disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. Finally, we provide region specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.

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6. Garvanska DH, Alvarado RE, Mundt FO, Nilsson E, Duel JK, Coscia F, Lindqvist R, Lokugamage K, Johnson BA, Plante JA, Morris DR, Vu MN, Estes LK, McLeland AM, Walker J, Crocquet-Valdes PA, Mendez BL, Plante KS, Walker DH, Weisser MB, Overby AK, Mann M, Menachery VD, Nilsson J. SARS-CoV-2 hijacks fragile X mental retardation proteins for efficient infection. bioRxiv : the preprint server for biology. 2023.

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1 and FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and have delayed disease onset in vivo . We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins for efficient infection and provides molecular insight to the possible underlying molecular defects in fragile X syndrome.

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7. Gonçalves AM, Sousa N, Jacinto L, Monteiro P. The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test. Frontiers in behavioral neuroscience. 2023; 17: 1205507.

INTRODUCTION: Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including SHANK3, a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the Shank3 gene (InsG3680) exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD. METHODS: To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes. RESULTS: Our results reveal that, in comparison to wild-type mice, Shank3 mutants display a strong behavioral preference toward silent regions of the arena. DISCUSSION: These data suggest that Shank3- mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.

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8. Hessl D, Rojas KM, Ferrer E, Espinal G, Famula J, Schneider A, Hagerman R, Tassone F, Rivera SM. A Longitudinal Study of Executive Function in Daily Life in Male Fragile X Premutation Carriers and Association with FXTAS Conversion. medRxiv : the preprint server for health sciences. 2023.

BACKGROUND: Men with fragile X-associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross-sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies have made it difficult to address this hypothesis. METHODS: This study included 66 FMR1 premutation carriers (PC) ranging from 40-78 years (Mean=59.5) and 31 well-matched healthy controls (HC) ages 40-75 (Mean 57.7) at baseline. Eighty-four participants returned for 2-5 follow up visits over a duration of 1 to 9 years (Mean=4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) was completed by participants and their spouses/partners at each visit. RESULTS: Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self-initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, BRIEF-A executive function problems at baseline significantly predicted later development of FXTAS. CONCLUSIONS: These findings suggest that executive function changes represent a prodrome of the later movement disorder.

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9. Jin J, Wang XQ, Yang X, Zhao N, Feng ZJ, Zang YF, Yuan LX. Abnormal individualized peak functional connectivity toward potential repetitive transcranial magnetic stimulation treatment of autism spectrum disorder. Human brain mapping. 2023.

Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic stimulation (rTMS). The left, right, and bilateral dorsolateral prefrontal cortices (DLPFC) have been used as rTMS treatment target regions for autism spectrum disorder (ASD), albeit with moderate efficacy. Thus, we aimed to develop an individualized localization method for rTMS treatment of ASD. We included 266 male ASDs and 297 male typically-developed controls (TDCs) from the Autism Brain Imaging Data Exchange Dataset. The nucleus accumbens (NAc) was regarded as a promising effective region, which was used as a seed and individualized peak FC strength in the DLPFC was compared between ASD and TDC. Correlation analysis was conducted between individualized peak FC strength and symptoms in ASD. We also investigated the spatial distribution of individualized peak FC locations in the DLPFC and conducted voxel-wise analysis to compare NAc-based FC between the two groups. ASD showed stronger peak FC in the right DLPFC related to TDC (Cohen’s d = -.19, 95% CI: -0.36 to -0.03, t = -2.30, p = .02). Moreover, negative correlation was found between the peak FC strength in the right DLPFC and Autism Diagnostic Observation Schedule (ADOS) scores, which assessed both the social communication and interaction (r = -.147, p = .04, uncorrected significant), and stereotyped behaviors and restricted interests (r = -.198, p = .02, corrected significant). Peak FC locations varied substantially across participants. No significant differences in NAc-based FC in the DLPFC were found in the voxel-wise comparison. Our study supports the use of individualized peak FC-guided precise rTMS treatment of male ASD. Moreover, stimulating the right DLPFC might alleviate core symptoms of ASD.

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10. Khalfe N, Goetz AR, Trent ES, Guzick AG, Smarason O, Kook M, Olsen S, Ramirez AC, Weinzimmer SA, Berry L, Schneider SC, Goodman WK, Storch EA. Psychometric properties of the revised children’s anxiety and depression scale (RCADS) for autistic youth without co-occurring intellectual disability. Journal of mood and anxiety disorders. 2023; 2.

Autistic youth often present with comorbid anxiety and depression yet there is a dearth of validated assessment tools. The Revised Children’s Anxiety and Depression Scale (RCADS) assesses internalizing symptoms but there is little psychometric data in autistic youth. Treatment-seeking autistic youth with anxiety or obsessive-compulsive symptoms (N = 74; age 6-14 years), and caregivers, were administered the RCADS-Parent, RCADS-Child, and assessments of internalizing, externalizing symptoms and social impairment indicative of autism. RCADS-Parent and RCADS-Child total anxiety scores demonstrated excellent internal consistency, and the six subscales demonstrated acceptable-to-good internal consistency. The RCADS-Child and Parent total anxiety scores were weakly correlated, and neither child age nor gender altered the strength of this association. Convergent validity was supported by moderate-to-strong correlations with clinician and parent-reported anxiety symptoms. Support for divergent validity was mixed. Results provide support for the RCADS-Parent and RCADS-Child as reliable, valid measures of internalizing symptoms in autistic youth.

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11. Levine MA, Chen H, Wodka EL, Deronda AC, Caffo BS, Ewen JB. A Multi-Trait Multi-Method Examination of Psychometric Instrument Performance in Autism Spectrum Disorder. Assessment. 2023: 10731911231198205.

Anecdotal evidence has suggested that rater-based measures (e.g., parent report) may have strong across-trait/within-individual covariance that detracts from trait-specific measurement precision; rater measurement-related bias may help explain poor correlation within Autism Spectrum Disorder (ASD) samples between rater-based and performance-based measures of the same trait. We used a multi-trait, multi-method approach to examine method-associated bias within an ASD sample (n = 83). We examined performance/rater-instrument pairs for attention, inhibition, working memory, motor coordination, and core ASD features. Rater-based scores showed an overall greater methodology bias (57% of variance in score explained by method), while performance-based scores showed a weaker methodology bias (22%). The degree of inter-individual variance explained by method alone substantiates an anecdotal concern associated with the use of rater measures in ASD.

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12. Li X, Hao S, Zou S, Tu X, Kong W, Jiang T, Chen JG. Cortex-restricted deletion of Foxp1 impairs barrel formation and induces aberrant tactile responses in a mouse model of autism. Molecular autism. 2023; 14(1): 34.

BACKGROUND: Many children and young people with autism spectrum disorder (ASD) display touch defensiveness or avoidance (hypersensitivity), or engage in sensory seeking by touching people or objects (hyposensitivity). Abnormal sensory responses have also been noticed in mice lacking ASD-associated genes. Tactile sensory information is normally processed by the somatosensory system that travels along the thalamus to the primary somatosensory cortex. The neurobiology behind tactile sensory abnormalities, however, is not fully understood. METHODS: We employed cortex-specific Foxp1 knockout (Foxp1-cKO) mice as a model of autism in this study. Tactile sensory deficits were measured by the adhesive removal test. The mice’s behavior and neural activity were further evaluated by the whisker nuisance test and c-Fos immunofluorescence, respectively. We also studied the dendritic spines and barrel formation in the primary somatosensory cortex by Golgi staining and immunofluorescence. RESULTS: Foxp1-cKO mice had a deferred response to the tactile environment. However, the mice exhibited avoidance behavior and hyper-reaction following repeated whisker stimulation, similar to a fight-or-flight response. In contrast to the wild-type, c-Fos was activated in the basolateral amygdala but not in layer IV of the primary somatosensory cortex of the cKO mice. Moreover, Foxp1 deficiency in cortical neurons altered the dendrite development, reduced the number of dendritic spines, and disrupted barrel formation in the somatosensory cortex, suggesting impaired somatosensory processing may underlie the aberrant tactile responses. LIMITATIONS: It is still unclear how the defective thalamocortical connection gives rise to the hyper-reactive response. Future experiments with electrophysiological recording are needed to analyze the role of thalamo-cortical-amygdala circuits in the disinhibiting amygdala and enhanced fearful responses in the mouse model of autism. CONCLUSIONS: Foxp1-cKO mice have tactile sensory deficits while exhibit hyper-reactivity, which may represent fearful and emotional responses controlled by the amygdala. This study presents anatomical evidence for reduced thalamocortical connectivity in a genetic mouse model of ASD and demonstrates that the cerebral cortex can be the origin of atypical sensory behaviors.

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13. MacDonald DN, Bedford SA, Olafson E, Park MTM, Devenyi GA, Tullo S, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Shinohara RT, Spencer MD, Suckling J, Taylor MJ, Thurm A, Lai MC, Chakravarty MM. Characterizing Subcortical Structural Heterogeneity in Autism. bioRxiv : the preprint server for biology. 2023.

Autism presents with significant phenotypic and neuroanatomical heterogeneity, and neuroimaging studies of the thalamus, globus pallidus and striatum in autism have produced inconsistent and contradictory results. These structures are critical mediators of functions known to be atypical in autism, including sensory gating and motor function. We examined both volumetric and fine-grained localized shape differences in autism using a large ( n =3145, 1045-1318 after strict quality control), cross-sectional dataset of T1-weighted structural MRI scans from 32 sites, including both males and females (assigned-at-birth). We investigated three potentially important sources of neuroanatomical heterogeneity: sex, age, and intelligence quotient (IQ), using a meta-analytic technique after strict quality control to minimize non-biological sources of variation. We observed no volumetric differences in the thalamus, globus pallidus, or striatum in autism. Rather, we identified a variety of localized shape differences in all three structures. Including age, but not sex or IQ, in the statistical model improved the fit for both the pallidum and striatum, but not for the thalamus. Age-centered shape analysis indicated a variety of age-dependent regional differences. Overall, our findings help confirm that the neurodevelopment of the striatum, globus pallidus and thalamus are atypical in autism, in a subtle location-dependent manner that is not reflected in overall structure volumes, and that is highly non-uniform across the lifespan.

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14. Mendez MA, Oakley B, Canitano R, San Jose Caceres A, Tinelli M, Knapp M, Cusack J, Parellada M, Violland P, Derk Plas JR, Canal-Bedia R, Bejarano-Martin A, Murphy DGM, Quoidbach V, Arango C. Autism care pathway in Europe. European psychiatry : the journal of the Association of European Psychiatrists. 2023: 1-29.

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15. Milutinovic L, Grujicic R, Mandic Maravic V, Joksic I, Ljubomirovic N, Pejovic Milovancevic M. Autism spectrum disorder and Coffin-Siris syndrome-Case report. Frontiers in psychiatry. 2023; 14: 1199710.

INTRODUCTION: Autism spectrum disorders (ASDs) are a group of developmental disorders characterized by deficits in social communicative skills and the occurrence of repetitive and/or stereotyped behaviors. Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degrees, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. In this study, we present a detailed description of autistic traits in a boy diagnosed with CSS and further discuss their genetic backgrounds. CASE DESCRIPTION: An 8-year-old boy with ASD, congenital anomalies, and neurological problems had been diagnosed with Coffin-Siris syndrome after genetic testing. Genetic testing revealed a heterozygous de novo pathogenic variant (class 5) c.1638_1647del in the ARID1B gene that is causative of Coffin-Siris syndrome but also other intellectual disability (ID)-related disorders, including autism. Tests that preceded the diagnoses, as well as congenital anomalies and developmental issues, were further described in an attempt to better present his phenotype. CONCLUSION: Both autism and ARID1B-related disorders are on a spectrum. This report points out the importance and necessity of further research regarding the genetic backgrounds of these disorders to understand their complex etiology.

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16. Minor GN, Hannula DE, Gordon A, Ragland JD, Iosif AM, Solomon M. Relational memory weakness in autism despite the use of a controlled encoding task. Frontiers in psychology. 2023; 14: 1210259.

INTRODUCTION: Recent work challenged past findings that documented relational memory impairments in autism. Previous studies often relied solely on explicit behavioral responses to assess relational memory integrity, but successful performance on behavioral tasks may rely on other cognitive abilities (e.g., executive functioning) that are impacted in some autistic individuals. Eye-tracking tasks do not require explicit behavioral responses, and, further, eye movements provide an indirect measure of memory. The current study examined whether memory-specific viewing patterns toward scenes differ between autistic and non-autistic individuals. METHODS: Using a long-term memory paradigm that equated for complexity between item and relational memory tasks, participants studied a series of scenes. Following the initial study phase, scenes were re-presented, accompanied by an orienting question that directed participants to attend to either features of an item (i.e., in the item condition) or spatial relationships between items (i.e., in the relational condition) that might be subsequently modified during test. At test, participants viewed scenes that were unchanged (i.e., repeated from study), scenes that underwent an « item » modification (an exemplar switch) or a « relational » modification (a location switch), and scenes that had not been presented before. Eye movements were recorded throughout. RESULTS: During study, there were no significant group differences in viewing directed to regions of scenes that might be manipulated at test, suggesting comparable processing of scene details during encoding. However, there was a group difference in explicit recognition accuracy for scenes that underwent a relational change. Marginal group differences in the expression of memory-based viewing effects during test for relational scenes were consistent with this behavioral outcome, particularly when analyses were limited to scenes recognized correctly with high confidence. Group differences were also evident in correlational analyses that examined the association between study phase viewing and recognition accuracy and between performance on the Picture Sequence Memory Test and recognition accuracy. DISCUSSION: Together, our findings suggest differences in the integrity of relational memory representations and/or in the relationships between subcomponents of memory in autism.

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17. Mohamed MS, Klann E. Autism- and epilepsy-associated EEF1A2 mutations lead to translational dysfunction and altered actin bundling. Proceedings of the National Academy of Sciences of the United States of America. 2023; 120(38): e2307704120.

Protein synthesis is a fundamental cellular process in neurons that is essential for synaptic plasticity and memory consolidation. Here, we describe our investigations of a neuron- and muscle-specific translation factor, eukaryotic Elongation Factor 1a2 (eEF1A2), which when mutated in patients results in autism, epilepsy, and intellectual disability. We characterize three EEF1A2 patient mutations, G70S, E122K, and D252H, and demonstrate that all three mutations decrease de novo protein synthesis and elongation rates in HEK293 cells. In mouse cortical neurons, the EEF1A2 mutations not only decrease de novo protein synthesis but also alter neuronal morphology, regardless of endogenous levels of eEF1A2, indicating that the mutations act via a toxic gain of function. We also show that eEF1A2 mutant proteins display increased tRNA binding and decreased actin-bundling activity, suggesting that these mutations disrupt neuronal function by decreasing tRNA availability and altering the actin cytoskeleton. More broadly, our findings are consistent with the idea that eEF1A2 acts as a bridge between translation and the actin cytoskeleton, which is essential for proper neuron development and function.

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18. Oates M, Bean A. Qualitative Analysis of the Experiences and Perspectives of Autistic Speech-Language Pathologists. American journal of speech-language pathology. 2023; 32(5): 2178-91.

PURPOSE: Supporting autistic speech-language pathologists (SLPs) is critical to expanding diversity within the field of speech-language pathology. The purpose of this study is to better understand how autistic SLPs reconcile tensions between their personal and professional experiences and negotiate the intersection of these identities. METHOD: Five certified SLPs, each of whom had a formal autism diagnosis or self-identified as autistic, engaged in a one-on-one semistructured conversation. The recorded interviews were transcribed manually. Following grounded theory analysis, multiple levels of coding were performed to construct a theoretical interpretation of the data. RESULTS: Four themes arose from the analysis. In the first, participants described their outlooks on their autistic identities and how these have changed over time. The second theme concerns interpersonal tensions and conflicts related to communication differences across neurotypes. In the third, participants reflected on the stigma and ableism they face in their careers, and concerns about disclosing their autistic identity in the workplace. The fourth comprised participants’ neurodiversity-affirming approaches to clinical practice with autistic clients. CONCLUSIONS: This study represents a first step toward understanding the unique strengths of autistic SLPs and the challenges they face. They can be better supported throughout their education, training, and careers. Our field must embrace and promote the neurodiversity paradigm to truly support all our colleagues and clients.

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19. Okoye C, Obialo-Ibeawuchi CM, Obajeun OA, Sarwar S, Tawfik C, Waleed MS, Wasim AU, Mohamoud I, Afolayan AY, Mbaezue RN. Early Diagnosis of Autism Spectrum Disorder: A Review and Analysis of the Risks and Benefits. Cureus. 2023; 15(8): e43226.

Autism spectrum disorder (ASD) is a neurodevelopmental condition made up of enduring challenges in social communication and interaction and the presence of repetitive and restricted behavior patterns. Early diagnosis of autism is crucial for timely intervention and improved long-term outcomes. This review aims to explore some of its signs and symptoms, look into some diagnostic tools, and analyze the benefits and risks associated with an early diagnosis of autism. The symptoms of ASD vary from child to child, some of which are: avoidance of eye contact, lack of response to names, excessive fear, and lack of interactive and pretend play. Early identification of these symptoms by caregivers and healthcare providers facilitates the need for diagnosis and appropriate interventions. Some screening and diagnostic tools that have been found to help make the diagnosis are the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F), the Social Communication Questionnaire (SCQ), the Parents’ Evaluation of Developmental Status (PEDS), and the Childhood Autism Rating Scale (CARS), amongst others. The benefits of early diagnosis include the opportunity for early intervention, which has been shown to enhance developmental outcomes and improve adaptive skills. Early identification allows for the implementation of specialized interventions tailored to the specific needs of individuals with autism, targeting social communication, language development, and behavioral challenges. Furthermore, early diagnosis enables families to access appropriate support services, educational resources, and community programs, facilitating better coping mechanisms, reducing parental stress, and increasing adult independence. However, early diagnosis of autism also entails certain risks. One significant concern is the potential for labeling and stigmatization, which can impact the child’s self-esteem and social interactions. There is a risk of overdiagnosis or misdiagnosis, leading to unnecessary interventions and treatments. Additionally, the diagnostic process can be lengthy, complex, and emotionally challenging for families, requiring comprehensive assessments by multidisciplinary teams. This review highlights the importance of a balanced approach when considering the benefits and risks of early diagnosis. Early identification allows for timely interventions that significantly improve developmental outcomes and quality of life for individuals with autism. To mitigate the risks, it is crucial to ensure accurate and reliable diagnostic procedures, support families throughout the process, and promote societal awareness and acceptance. We also highlighted some future directions in the management of autism, including the use of biomarkers and the use of artificial intelligence and learning for diagnosing ASD.

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20. Rasheed Z. Autism in Australia: Understanding, challenges, and support. International journal of health sciences. 2023; 17(5): 1-4.

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21. Song AY, Bulka CM, Niemiec SS, Kechris K, Boyle KE, Marsit CJ, O’Shea TM, Fry RC, Lyall K, Fallin MD, Volk HE, Ladd-Acosta C. Accelerated epigenetic age at birth and child emotional and behavioura development in early childhood: a meta-analysis of four prospective cohort studies in ECHO. Epigenetics. 2023; 18(1): 2254971.

Background: ‘Epigenetic clocks’ have been developed to accurately predict chronologic gestational age and have been associated with child health outcomes in prior work.Methods: We meta-analysed results from four prospective U.S cohorts investigating the association between epigenetic age acceleration estimated using blood DNA methylation collected at birth and preschool age Childhood Behavior Checklist (CBCL) scores.Results: Epigenetic ageing was not significantly associated with CBCL total problem scores (β = 0.33, 95% CI: -0.95, 0.28) and DSM-oriented pervasive development problem scores (β = -0.23, 95% CI: -0.61, 0.15). No associations were observed for other DSM-oriented subscales.Conclusions: The meta-analysis results suggest that epigenetic gestational age acceleration is not associated with child emotional and behavioural functioning for preschool age group. These findings may relate to our study population, which includes two cohorts enriched for ASD and one preterm birth cohort.; future work should address the role of epigenetic age in child health in other study populations.Abbreviations: DNAm: DNA methylation; CBCL: Child Behavioral Checklist; ECHO: Environmental Influences on Child Health Outcomes; EARLI: Early Autism Risk Longitudinal Investigation; MARBLES: Markers of Autism Risk in Babies – Learning Early Signs; ELGAN: Extremely Low Gestational Age Newborns; ASD: autism spectrum disorder; BMI: body mass index; DSM: Diagnostic and Statistical Manual of Mental Disorders.

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22. Waizbard-Bartov E, Ferrer E, Heath B, Andrews DS, Rogers S, Kerns CM, Wu Nordahl C, Solomon M, Amaral DG. Changes in the severity of autism symptom domains are related to mental health challenges during middle childhood. Autism : the international journal of research and practice. 2023: 13623613231195108.

For many autistic children, the severity of their autism symptoms changes during middle childhood. We studied whether these changes are associated with the emergence of other mental health challenges such as anxiety and attention-deficit hyperactivity disorder. Children who had increased social-communication challenges had more anxiety and attention-deficit hyperactivity disorder symptoms and disruptive behavior problems than other children. Children who decreased their restricted and repetitive behaviors, on the contrary, had more anxiety. We discuss why these changes in autism symptoms may lead to increases in other mental health concerns.

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23. Wang Q, Tang B, Hao S, Wu Z, Yang T, Tang J. Forniceal deep brain stimulation in a mouse model of Rett syndrome increases neurogenesis and hippocampal memory beyond the treatment period. Brain stimulation. 2023.

BACKGROUND: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT. OBJECTIVES: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice. METHODS: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual and cued fear memory at different time points after DBS. We then examined neurogenesis, DGC apoptosis, and the expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) after DBS by immunohistochemistry. RESULTS: After two weeks of forniceal DBS, memory improvements lasted between 6 and 9 weeks. Repeating DBS every 6 weeks was sufficient to maintain the improvement. Forniceal DBS stimulated the birth of more MeCP2-positive than MeCP2-negative DGCs and had no effect on DGC survival. It also increased the expression of BDNF but not VEGF in the RTT mouse dentate gyrus. CONCLUSION: Improvements in learning and memory from forniceal DBS in RTT mice extends well beyond the treatment period and can be maintained by repeated DBS. Stimulation of BDNF expression correlates with improvements in hippocampal neurogenesis and memory benefits.

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24. Wang X, Tang R, Wei Z, Zhan Y, Lu J, Li Z. The enteric nervous system deficits in autism spectrum disorder. Frontiers in neuroscience. 2023; 17: 1101071.

Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.

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25. Wang Y, Wang F, Kong Y, Gao T, Zhu Q, Han L, Sun B, Guan L, Zhang Z, Qian Y, Xu L, Li Y, Fang H, Jiao G, Ke X. High definition transcranial direct current stimulation of the Cz improves social dysfunction in children with autism spectrum disorder: A randomized, sham, controlled study. Autism research : official journal of the International Society for Autism Research. 2023.

The purpose of this study was to determine the effect of the Cz of high-definition 5-channel tDCS (HD-tDCS) on social function in 4-12 years-old children with autism spectrum disorder (ASD). This study was a randomized, double-blind, pseudo-controlled trial in which 45 ASD children were recruited and divided into three groups with sex, age, and rehabilitation treatment as control variables. Each group of 15 children with ASD was randomly administered active HD-tDCS with the Cz as the central anode, active HD-tDCS with the left dorsolateral prefrontal cortex (F3) as the central anode, and sham HD-tDCS with the Cz as the central anode with 14 daily sessions in 3 weeks. The Social Responsiveness Scale Chinese Version (SRS-Chinese Version) was compared 1 week after stimulation with values recorded 1 week prior to stimulation. At the end of treatment, both the anodal Cz and anodal left DLFPC tDCS decreased the measures of SRS-Chinese Version. The total score of SRS-Chinese Version decreased by 13.08%, social cognition decreased by 18.33%, and social communication decreased by 10.79%, which were significantly improved over the Cz central anode active stimulation group, especially in children with young age, and middle and low function. There was no significant change in the total score and subscale score of SRS-Chinese Version over the Cz central anode sham stimulation group. In the F3 central anode active stimulation group, the total score of SRS-Chinese Version decreased by 13%, autistic behavior decreased by 19.39%, and social communication decreased by 14.39%, which were all significantly improved. However, there was no significant difference in effect between the Cz and left DLPFC stimulation conditions. HD-tDCS of the Cz central anode may be an effective treatment for social dysfunction in children with ASD.

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26. Wang Y, Yu S, Li M. Neurovascular crosstalk and cerebrovascular alterations: an underestimated therapeutic target in autism spectrum disorders. Frontiers in cellular neuroscience. 2023; 17: 1226580.

Normal brain development, function, and aging critically depend on unique characteristics of the cerebrovascular system. Growing evidence indicated that cerebrovascular defects can have irreversible effects on the brain, and these defects have been implicated in various neurological disorders, including autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder with heterogeneous clinical manifestations and anatomical changes. While extensive research has focused on the neural abnormalities underlying ASD, the role of brain vasculature in this disorder remains poorly understood. Indeed, the significance of cerebrovascular contributions to ASD has been consistently underestimated. In this work, we discuss the neurovascular crosstalk during embryonic development and highlight recent findings on cerebrovascular alterations in individuals with ASD. We also discuss the potential of vascular-based therapy for ASD. Collectively, these investigations demonstrate that ASD can be considered a neurovascular disease.

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27. Williams EH, Thompson NM, McCray G, Chakrabarti B. Autistic traits modulate the influence of face masks on gaze perception. Scientific reports. 2023; 13(1): 14921.

Detecting when others are looking at us is a crucial social skill. Accordingly, a range of gaze angles is perceived as self-directed; this is termed the « cone of direct gaze » (CoDG). Multiple cues, such as nose and head orientation, are integrated during gaze perception. Thus, occluding the lower portion of the face, such as with face masks during the COVID-19 pandemic, may influence how gaze is perceived. Individual differences in the prioritisation of eye-region and non-eye-region cues may modulate the influence of face masks on gaze perception. Autistic individuals, who may be more reliant on non-eye-region directional cues during gaze perception, might be differentially affected by face masks. In the present study, we compared the CoDG when viewing masked and unmasked faces (N = 157) and measured self-reported autistic traits. The CoDG was wider for masked compared to unmasked faces, suggesting that reduced reliability of lower face cues increases the range of gaze angles perceived as self-directed. Additionally, autistic traits positively predicted the magnitude of CoDG difference between masked and unmasked faces. This study provides crucial insights into the effect of face masks on gaze perception, and how they may affect autistic individuals to a greater extent.

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28. Zhang Q, Wang Y, Tao J, Xia R, Zhang Y, Liu Z, Cheng J. Sex-biased single cell genetic landscape in mice with autism spectrum disorder. Journal of genetics and genomics = Yi chuan xue bao. 2023.

Autistic spectrum disorder (ASD) is a male-biased heterogeneous neurodevelopmental disorder that affects approximately 1%-2% of the population. Prenatal exposure to valproic acid (VPA) is a recognized risk factor for ASD, but the cellular and molecular basis of VPA-induced ASD at the single-cell resolution is unclear. Here, we aimed to compare the cellular and molecular differences in the hippocampus between male and female prenatal mice with ASD at the single-cell transcriptomic level. The transcriptomes of more than 45,000 cells were assigned to 12 major cell types, including neurons, glial cells, vascular cells, and immune cells. Cell type-specific genes with altered expression after prenatal VPA exposure were analyzed, and the largest number of differentially expressed genes (DEGs) were found in neurons, choroid plexus epithelial cells, and microglia. In microglia, several pathways related to inflammation were found in both males and females, including the TNF, NF-κB, Toll-like receptor, and MAPK signaling pathways, which are important for the induction of autistic-like behavior. Additionally, we noted that several X-linked genes, including Bex1, Bex3, and Gria3, were among the male-specific DEGs of neurons. This pioneering study describes the landscape of the transcriptome in the hippocampus of autistic individuals. The elucidation of sexual differences could provide innovative strategies for the prevention and treatment of ASD.

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