1. Artis J, Arunachalam S. Semantic and Syntactic Properties of Words and the Receptive-Expressive Gap in Autistic and Non-Autistic Children. Journal of speech, language, and hearing research : JSLHR. 2023: 1-21.

PURPOSE: The goal of this work was to examine the semantic and syntactic properties of the vocabularies of autistic and non-autistic infants and toddlers to see if children in these two groups know different kinds of words. We focused on both receptive and expressive vocabularies. For expressive vocabulary, we looked only at the « active » lexicon: Of those words that are already in children’s receptive vocabulary, we asked which ones they also produce. METHOD: We used an existing data set of 346 parent report vocabulary checklists (MacArthur-Bates Communicative Development Inventory: Words and Gestures) from 41 autistic and 27 non-autistic children at multiple timepoints between the ages of 6 and 43 months. We coded the words on the checklists for various semantic and syntactic properties and evaluated which properties predicted whether children understood and produced those words. RESULTS: Overall, we replicated a common finding that autistic children have smaller receptive vocabularies than non-autistic children, but we found that of the words they understand, autistic children produce a similar proportion of those words as non-autistic children. While we found that some syntactic properties are more or less likely to be represented in children’s early vocabularies (e.g., nouns are more likely to be understood and produced than words that are not nouns), these patterns did not differ across autistic and non-autistic children. CONCLUSIONS: The semantic and syntactic compositions of autistic and non-autistic children’s vocabularies are similar. Thus, while receptive vocabularies are relatively smaller for autistic children, they do not appear to have specific difficulty with words that have particular syntactic or semantic properties, or with adding words to the expressive vocabulary that they already understand.

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2. Atia AA, Ashour RH, Zaki MM, Rahman KM, Ramadan NM. The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy. Psychopharmacology. 2023.

RATIONALE: Risperidone is the first antipsychotic to be approved by Food and Drug Administration (FDA) for treating autism spectrum disorder (ASD). The potential efficacy of metformin in preventing and/or controlling ASD behavioral deficits was also recently reported. Suppression of hippocampus autophagy was suggested as a potential pathologic mechanism in ASD. OBJECTIVES: Is metformin’s ability to improve ASD clinical phenotype driven by its autophagy-enhancing properties? And does hippocampus autophagy enhancement underlie risperidone’s efficacy as well? Both questions are yet to be answered. METHODS: The effectiveness of metformin on alleviation of ASD-like behavioral deficits in adolescent rats exposed prenatally to valproic acid (VPA) was compared to that of risperidone. The potential modulatory effects of risperidone on hippocampal autophagic activity were also assessed and compared to those of metformin. RESULTS: Male offspring exposed to VPA during gestation exhibited marked anxiety, social impairment and aggravation of stereotyped grooming; such deficits were efficiently rescued by postnatal risperidone or metformin therapy. This autistic phenotype was associated with suppressed hippocampal autophagy; as evidenced by reduced gene/dendritic protein expression of LC3B (microtubule-associated proteins 1 light chain 3B) and increased somatic P62 (Sequestosome 1) protein aggregates. Interestingly, compared to risperidone, the effectiveness of metformin in controlling ASD symptoms and improving hippocampal neuronal survival was well correlated to its ability to markedly induce pyramidal neuronal LC3B expression while lowering P62 accumulation. CONCLUSIONS: Our work highlights, for the first time, positive modulation of hippocampus autophagy as potential mechanism underlying improvements in autistic behaviors, observed with metformin, as well as risperidone, therapy.

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3. Harris E. Autism Prevalence Has Been on the Rise in the US for Decades-And That’s Progress. Jama. 2023.

This Medical News article discusses advancements in understanding and characterizing autism over the past 20 years. eng.

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4. Kirby L, Payne KL. Knowledge of autism gained by learning from people through a local UK Autism Champion Network: A health and social care professional perspective. Autism : the international journal of research and practice. 2023: 13623613231167902.

The Autism Act 10 Years On found few autistic adults thought health and social care professionals had a good understanding of autism. Autism training has been made law in the United Kingdom for health and social care staff to tackle health inequality. The county wide Autism Champion Network evaluated here is an equal partnership of interested staff across sectors (Autism Champions) and autistic experts by virtue of lived experience (Autism Advisory Panel). With knowledge flowing both ways, the Autism Champions take learning back to teams to support continuous development of services to meet autistic need. Seven health and social sector professionals from the Network participated in semi-structured interviews on sharing knowledge of autism gained with their teams. All participants provide care and support for autistic people, some working in specialist positions. Results showed that developing new relationships with people outside their own team to signpost to, answer questions and share resources, and informal learning from autistic people, was more valued and used in practice than information gained from presentations. These results have implications in developing learning for those who need above a basic knowledge of autism and may be useful for others considering setting up an Autism Champion Network.

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5. Krishnappa Babu PR, Aikat V, Di Martino JM, Chang Z, Perochon S, Espinosa S, Aiello R, K LHC, Compton S, Davis N, Eichner B, Flowers J, Franz L, Dawson G, Sapiro G. Blink rate and facial orientation reveal distinctive patterns of attentional engagement in autistic toddlers: a digital phenotyping approach. Scientific reports. 2023; 13(1): 7158.

Differences in social attention are well-documented in autistic individuals, representing one of the earliest signs of autism. Spontaneous blink rate has been used to index attentional engagement, with lower blink rates reflecting increased engagement. We evaluated novel methods using computer vision analysis (CVA) for automatically quantifying patterns of attentional engagement in young autistic children, based on facial orientation and blink rate, which were captured via mobile devices. Participants were 474 children (17-36 months old), 43 of whom were diagnosed with autism. Movies containing social or nonsocial content were presented via an iPad app, and simultaneously, the device’s camera recorded the children’s behavior while they watched the movies. CVA was used to extract the duration of time the child oriented towards the screen and their blink rate as indices of attentional engagement. Overall, autistic children spent less time facing the screen and had a higher mean blink rate compared to neurotypical children. Neurotypical children faced the screen more often and blinked at a lower rate during the social movies compared to the nonsocial movies. In contrast, autistic children faced the screen less often during social movies than during nonsocial movies and showed no differential blink rate to social versus nonsocial movies.

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6. Lim A, Brewer N, Aistrope D, Young RL. Response format changes the reading the mind in the eyes test performance of autistic and non-autistic adults. Autism : the international journal of research and practice. 2023: 13623613231167226.

Recognizing and understanding the perspectives of others-also called theory of mind-is important for effective communication. Studies have found that some autistic individuals have greater difficulty with theory of mind compared to non-autistic individuals. One purported theory of mind measure is the Reading the Mind in the Eyes Test (RMET). This test presents participants with photographs of pairs of eyes and asks them to identify the emotion displayed by each pair of eyes from four choices. Some researchers have argued that the multiple-choice format of the RMET may not be an accurate measure of theory of mind, as participants could simply be guessing or using a process of elimination to select the correct answer. Participants may also be disadvantaged if they are not familiar with the specific emotion words used in the multiple-choice answers. We examined whether a free-report (open-ended) format RMET would be a more valid measure of theory of mind than the multiple-choice RMET. Autistic and non-autistic adults performed better on the multiple-choice RMET than the free-report RMET. However, both versions successfully differentiated autistic and non-autistic adults, irrespective of their level of verbal ability. Performance on both versions was also correlated with another well-validated adult measure of theory of mind. Thus, the RMET’s multiple-choice format does not, of itself, appear to underpin its ability to differentiate autistic and non-autistic adults.

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7. McGrew J, Yu Y, Ruble L, Murray DS. Predictive Analysis of Parent Activation and Autism. Journal of autism and developmental disorders. 2023.

We examined parent activation in families with autistic children over time. Activation is one’s belief, knowledge, and persistence in obtaining and managing one’s care (e.g., patient activation) and others (e.g., parent activation) and is associated with better outcomes. Four aims were examined: the associations between baseline parent activation and follow up treatment/outcome, between changes in activation and changes in treatment/outcome, differences in activation and treatment/outcome across demographic groups (e.g., gender, race, ethnicity, and income) and comparison of results using three different assessment approaches of parent activation, the Guttman scale (standard approach) and two factor subscales (Yu et al., in J Autism Dev Disord 53:110-120, 2023). The first factor tapped into behaviors aligned with highly active, assertive parental actions (Factor 1: Activated). The second tapped into behaviors representative of uncertainty, passivity, being overwhelmed, with growing awareness of the need for activation (Factor 2: Passive). Findings varied with assessment methods applied. The two subscales assessment approach produced the strongest effect sizes. Baseline activation was related to improved child outcomes at follow-up for Factor 1: Activated and to poorer child outcomes at follow-up for Factor 2: Passive. Changes in activation were unrelated to changes in treatment/outcomes. Outcomes differed based on the activation assessment approach used. Against expectations, activation remained the same over time. Further, no differences in outcomes were observed based on race, ethnicity, or family income. The results suggest that parent activation may behave differently than patient activation based on prior studies. More research is warranted on activation of parents of autistic children.

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8. Mei D, Parrini E, Bianchini C, Ricci ML, Guerrini R. Autism and mild epilepsy associated with a de novo missense pathogenic variant in the GTPase effector domain of DNM1. American journal of medical genetics Part C, Seminars in medical genetics. 2023.

Dynamin 1 is a GTPase protein involved in synaptic vesicle fission, which facilitates the exocytosis of neurotransmitters necessary for normal signaling. Pathogenic variants in the DNM1 gene are associated with intractable epilepsy, often manifested as infantile spasms at onset, developmental delay, and a movement disorder, and are located in the GTPase and middle domains of the protein. We describe a 36-year-old man with autism and moderate intellectual disability who experienced only a few generalized seizures between the age 16 and 30 years. Using a whole sequencing approach, we identified the c.1994T>C p.(Leu665Pro) de novo novel missense pathogenic variant in the GTPase effector domain (GED) of the DNM1 protein. Structural analyses suggest that this substitution impairs both the stalk formation and its interactions, known to be important for the dynamin-1 physiological cellular function. Our data expand the spectrum of phenotypes associated with pathogenic variants in the DNM1 gene, linking a variant in the GED domain with autism and onset in the adolescence of mild epilepsy, a phenotypic presentation remarkably different from the early infantile epileptic encephalopathy associated with pathogenic variants in the GTPase or middle domains.

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9. Min S, Gandal MJ, Kopp RF, Liu C, Chen C. No Increased Detection of Nucleic Acids of CNS-related Viruses in the Brains of Patients with Schizophrenia, Bipolar Disorder, and Autism Spectrum Disorder. Schizophrenia bulletin. 2023; 49(3): 551-8.

BACKGROUND AND HYPOTHESIS: Viral infections are increasingly recognized in the etiology of psychiatric disorders based on epidemiological and serological studies. Few studies have analyzed viruses directly within the brain and no comprehensive investigation of viral infection within diseased brains has been completed. This study aims to determine whether viral infection in brain tissues is a risk factor for 3 major psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. STUDY DESIGN: This study directly evaluated the presence of viral DNA or RNA in 1569 brains of patients and controls using whole-genome sequencing and RNA sequencing data with 4 independent cohorts. The PathSeq tool was used to identify known human viruses in the genome and transcriptome of patients and controls. STUDY RESULTS: A variety of DNA and RNA viruses related to the central nervous system were detected in the brains of patients with major psychiatric disorders, including viruses belonging to Herpesviridae, Polyomaviridae, Retroviridae, Flaviviridae, Parvoviridae, and Adenoviridae. However, no consistent significant differences were found between patients and controls in terms of types and amount of virus detected at both DNA and RNA levels. CONCLUSIONS: The findings of this study do not suggest an association between viral infection in postmortem brains and major psychiatric disorders.

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10. Morrisroe KA, Longo K, Pebley P, Jain L. Fitting in an Unfit Society With Autism Spectrum Disorder: Case Report. Cureus. 2023; 15(3): e36966.

Evaluating behavioral mimicking is important in healthcare providers’ everyday functioning with an increased presentation of Tourette syndrome-like cases during the COVID-19 pandemic, seen due to the popular video creators on social media (e.g., TikTok) exhibiting these behaviors. Individuals with autism spectrum disorder (ASD) face difficulties with connection and assimilation, and they adapt by camouflaging their behaviors to fit with those of the neurotypical majority. Our team evaluated the behaviors of one individual with ASD to establish whether camouflaging was playing a role in her psychiatric stabilization in our inpatient psychiatric unit. We present a case of a 30-year-old female with ASD, admitted to our long-term inpatient psychiatric facility for significant mood dysregulation that persisted despite numerous treatment approaches (mediations, groups, etc.). While her initial behaviors included head banging and self-induced falls, her behaviors seemed to change based on those of her peers, in an apparent attempt to camouflage into the social environment within the unit. She also appeared to learn new self-harm behaviors, such as skin picking, from peers around her. The team was able to establish a temporal link between some instances of peers exhibiting specific behaviors and our patient engaging in similar behavior. Although inpatient units effectively manage long-term stabilization in other psychiatric disorders, these environments are not designed for individuals with ASD. Treatment teams should recognize the malleability of behaviors in patients with ASD and must identify and manage behavioral mimicking early during inpatient psychiatric treatment; otherwise, it may lead to significant harm.

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11. Nuske P, Ba B, Khan M, Palermo B, Ajanaku BAB, Pellecchia N, Vivanti P, Mazefsky P, Brookman-Frazee P, McPartland P, Goodwin P, Mandell S. Systematic Review: Emotion Dysregulation and Challenging Behavior Interventions for Children andAdolescents with Autism with Graded Key Evidence-Based Strategy Recommendations. Research square. 2023.

Challenging behavior, such as aggression, is highly prevalent in children and adolescents with autism and can have a devastating impact. Previous reviews of challenging behavior interventions did not include interventions targeting emotion dysregulation, a common cause of challenging behavior. We reviewed emotion dysregulation and challenging behavior interventions for preschoolers to adolescents to determine which evidence-based strategies have the most empirical support for reducing/preventing emotion dysregulation/challenging behavior. We reviewed 95 studies, including 29 group and 66 single-case designs. We excluded non-behavioral/psychosocial interventions and those targeting internalizing symptoms only. We applied a coding system to identify discrete strategies based on autism practice guidelines with the addition of strategies common in childhood mental health disorders, and an evidence grading system. Strategies with the highest quality evidence (multiple randomized controlled trials with low bias risk) were Parent-Implemented Intervention, Emotion Regulation Training, Reinforcement, Visual Supports, Cognitive Behavioral/Instructional Strategies and Antecedent-Based Interventions. Regarding outcomes, most studies included challenging behaviors measures while few included emotion dysregulation measures. This review highlights the importance of teaching emotion-regulation skills explicitly, positively reinforcing replacement/alternative behaviors, using visuals and metacognition, addressing stressors proactively, and involving parents. It also calls for more rigorously-designed studies and for including emotion dysregulation as an outcome/mediator in future trials.

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12. Robinson BG, Oster BA, Robertson K, Kaltschmidt JA. Loss of ASD-Related Molecule Caspr2 Affects Colonic Motility in Mice. bioRxiv : the preprint server for biology. 2023.

Gastrointestinal (GI) symptoms are highly prevalent among individuals with autism spectrum disorder (ASD), but the molecular link between ASD and GI dysfunction remains poorly understood. The enteric nervous system (ENS) is critical for normal GI motility and has been shown to be altered in mouse models of ASD and other neurological disorders. Contactin-associated protein-like 2 (Caspr2) is an ASD-related synaptic cell-adhesion molecule necessary for regulating sensory function in the central and peripheral nervous system. In this study, we examine the role of Caspr2 in GI motility by characterizing Caspr2’s expression in the ENS and assessing ENS organization and GI function in Caspr2 mutant mice. We find that Caspr2 is predominantly expressed in enteric sensory neurons in both the small intestine and colon. We further assess colonic motility in Caspr2 mutants using an ex-vivo motility monitor and show altered colonic contractions and faster expulsion of artificial pellets. The organization of neurons within the myenteric plexus remains unchanged. Our results suggest a role for enteric sensory neurons in ASD-related GI dysmotility, a finding relevant to consider in the treatment of ASD-related GI symptoms. LAY SUMMARY: Autism spectrum disorder (ASD) patients experience sensory abnormalities and chronic gastrointestinal (GI) problems. We ask if the ASD-related synaptic cell-adhesion molecule Caspr2, associated with ASD-related hypersensitivity in the central and peripheral nervous system, is present and/or plays a role in GI function in mice. Results show Caspr2 is present in enteric sensory neurons; lack of Caspr2 alters GI motility, suggesting enteric sensory dysfunction may contribute to ASD-related GI symptoms.

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13. Rosqvist HB, Nygren A, O’Donoghue S. Moving Through a Textual Space Autistically. The Journal of medical humanities. 2023.

This article is an investigation of neurodivergent reading practices. It is a collectively written paper where the focus is as much on an autoethnographic exploration of our autistic readings of autism/autistic fiction as it is on the read texts themselves. The reading experiences described come primarily from Yoon Ha Lee’s Dragon Pearl (2019) and Dahlia Donovan’s The Grasmere Cottage Mystery (2018), which we experience as opposite each other in how they depict their neurodivergent characters and speak to us as autistic readers. Through the article, we describe a formation of neurodivergent (critical) collective readings of autism/autistic fiction. The article contributes to an academic and activistic discourse around neurodivergent reader responses and power relations between neurodivergent and neurotypical readers and authors.

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14. Ruffing S, Ullrich C, Flotats-Bastardas M, Poryo M, Meyer S. [Assessment of the importance of neuropediatric diagnostics in the initial clarification of autism]. Wiener medizinische Wochenschrift (1946). 2023.

BACKGROUND: The diagnostics of autism spectrum disorder is complex due to missing biological markers and numerous comorbidities. The aim was to assess the role of neuropediatric diagnostics and to develop a standard operating procedure for a targeted assessment. METHOD: All patients presenting to the neuropediatric outpatient clinic at Saarland University Hospital between April 2014 and December 2017 with ICD code F84 pervasive developmental disorders were included. RESULTS: A total of 82 patients were included (male 78%, female 22%; mean age 5.9 ± 2.9 years, range 2-16 years). The most frequent examination was electroencephalography (EEG) (74/82; 90.2%) with pathological findings in 33.8% (25/74). Based on the history and/or EEG epilepsy was diagnosed in 19.5% (16/82). Magnetic resonance imaging (MRI) was performed in 49/82 (59.8%) patients, 22/49 (44.9%) showed at least 1 cerebral abnormality and definite pathologies could be detected in 63.6% (14/22). A metabolic diagnostic work-up was performed in 44/82 (53.7%) cases and in 5/44 (11.4%) it resulted in a diagnosis or suspicion of a metabolic disease. Genetic testing results were available in 29/82 (35.4%) children and 12/29 (41.4%) showed abnormal results. Delay in motor development was more frequently associated with comorbidities, EEG abnormalities, epilepsy and abnormalities in metabolic and genetic testing. CONCLUSION: Neuropediatric examination in cases of suspected autism should include a detailed history, a thorough neurological examination and an EEG. An MRI, comprehensive metabolic and genetic testing are only recommended if clinically indicated.

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15. Sunagawa M. How much of my true self can i show? social adaptation in autistic women: a qualitative study. BMC psychology. 2023; 11(1): 144.

BACKGROUND: Social adaptation is often aimed at supporting autistic people, yet its specific goals may not include their actual perspectives. That is, the state of adaptation is judged based on the standards and values of non-autistic people. This qualitative study focused on autistic women’s perceptions of social adaptation and examined their lived experiences in daily life, as adaptive behaviors have often been reported as a « female autism phenotype. » METHODS: Semi-structured interviews were conducted face-to-face with ten autistic women aged 28-50 years (M = 36.7; standard SD = 7.66). The analysis was conducted based on the grounded theory approach. RESULTS: Two core perceptions were identified: maintaining stable relationships and fulfilling social roles based on past experiences of « maladaptation. » The participants sought adaptations within a reasonable range and adjusted their balance with society to maintain stability in their daily lives. CONCLUSION: The findings indicated that autistic women’s perceptions of adaptation were based on the accumulation of past negative experiences. Further harmful efforts should be prevented. Support for autistic people to make their own choices in life is also important. Moreover, autistic women need a place where they can be themselves and be accepted as they are. This study showed the importance of changing the environment rather than modifying autistic people to adapt to a society.

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16. Wang S, Li X. A revisit of the amygdala theory of autism: Twenty years after. Neuropsychologia. 2023; 183: 108519.

The human amygdala has long been implicated to play a key role in autism spectrum disorder (ASD). Yet it remains unclear to what extent the amygdala accounts for the social dysfunctions in ASD. Here, we review studies that investigate the relationship between amygdala function and ASD. We focus on studies that employ the same task and stimuli to directly compare people with ASD and patients with focal amygdala lesions, and we also discuss functional data associated with these studies. We show that the amygdala can only account for a limited number of deficits in ASD (primarily face perception tasks but not social attention tasks), a network view is, therefore, more appropriate. We next discuss atypical brain connectivity in ASD, factors that can explain such atypical brain connectivity, and novel tools to analyze brain connectivity. Lastly, we discuss new opportunities from multimodal neuroimaging with data fusion and human single-neuron recordings that can enable us to better understand the neural underpinnings of social dysfunctions in ASD. Together, the influential amygdala theory of autism should be extended with emerging data-driven scientific discoveries such as machine learning-based surrogate models to a broader framework that considers brain connectivity at the global scale.

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17. Washington P, Wall DP. A Review of and Roadmap for Data Science and Machine Learning for the Neuropsychiatric Phenotype of Autism. Annual review of biomedical data science. 2023.

Autism spectrum disorder (autism) is a neurodevelopmental delay that affects at least 1 in 44 children. Like many neurological disorder phenotypes, the diagnostic features are observable, can be tracked over time, and can be managed or even eliminated through proper therapy and treatments. However, there are major bottlenecks in the diagnostic, therapeutic, and longitudinal tracking pipelines for autism and related neurodevelopmental delays, creating an opportunity for novel data science solutions to augment and transform existing workflows and provide increased access to services for affected families. Several efforts previously conducted by a multitude of research labs have spawned great progress toward improved digital diagnostics and digital therapies for children with autism. We review the literature on digital health methods for autism behavior quantification and beneficial therapies using data science. We describe both case-control studies and classification systems for digital phenotyping. We then discuss digital diagnostics and therapeutics that integrate machine learning models of autism-related behaviors, including the factors that must be addressed for translational use. Finally, we describe ongoing challenges and potential opportunities for the field of autism data science. Given the heterogeneous nature of autism and the complexities of the relevant behaviors, this review contains insights that are relevant to neurological behavior analysis and digital psychiatry more broadly. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 6 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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18. Wehrle S, Grice M, Vogeley K. Filled Pauses Produced by Autistic Adults Differ in Prosodic Realisation, but not Rate or Lexical Type. Journal of autism and developmental disorders. 2023.

We examined the use of filled pauses in conversations between homogeneous pairs of autistic and non-autistic adults. A corpus of semi-spontaneous speech was used to analyse the rate, lexical type (nasal « uhm » or non-nasal « uh »), and prosodic realisation (rising, level or falling) of filled pauses. We used Bayesian modelling for statistical analysis. We found an identical rate of filled pauses and an equivalent preference of « uhm » over « uh » across groups, but also a robust group-level difference regarding the intonational realisation of filled pauses: non-autistic controls produced a considerably higher proportion of filled pause tokens realised with the canonical level pitch contour than autistic speakers. Despite the fact that filled pauses are a frequent and impactful part of speech, previous work on their conversational use in autism spectrum disorder (ASD) is limited. Our account is the first to analyse the intonational realisation of filled pauses in ASD and the first to investigate conversations between autistic adults in this context. Our results on rate and lexical type can help to contextualise previous research, while the novel findings on intonational realisation set the stage for future investigations.

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19. Wei X, Zhang S, Zhang J, Yu J. Mathematics performance, response time, and enjoyment of eighth-grade autistic students and their general education peers. Autism : the international journal of research and practice. 2023: 13623613231168241.

For autistic students receiving special education services, little is known about their relative strengths, weaknesses, and enjoyment across different math content areas; their overall math interest and persistence are also not well-studied. Using the 2017 eighth-grade National Assessment of Education Progress data, this study finds, relative to general education peers with the same math proficiency level, autistic students scored higher and exhibited faster speed in solving visuospatial problems (e.g. identifying figures), but scored lower on math word problems with complex language or social context. Autistic students reported a higher level of enjoyment in solving math problems related to finding areas of shapes or figures but a lower level of persistence than their non-autistic, general education peers. Our work points out the need to help autistic students overcome their weaknesses in word problems and develop their mathematical persistence.

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