1. Corrigendum to Exploring the health of families with a child with autism. Autism : the international journal of research and practice. 2021; 25(5): 1497-8.

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2. Axeen E, Bell E, Robichaux Viehoever A, Schreiber JM, Sidiropoulos C, Goodkin HP. Results of the First GNAO1-Related Neurodevelopmental Disorders Caregiver Survey. Pediatric neurology. 2021; 121: 28-32.

BACKGROUND: We sought to expand our knowledge of the clinical spectrum of GNAO1-related neurodevelopmental disorders through a caregiver survey reviewing medical and developmental history and development of epilepsy and movement disorders. METHODS: An online survey was administered to caregivers of individuals diagnosed with GNAO1 pathogenic variants. RESULTS: Eighty-two surveys were completed. Nearly all (99%) reported the first symptom of concern by age one year with the most frequently identified concerns as hypotonia (68%), developmental delay (67%), seizures (29%), difficulty feeding (23%), and abnormal movements (20%). All caregivers reported developmental delays with a spectrum of severity. Movement disorders (76%) were more common than epilepsy (52%), although 33% reported both. The onset of seizures tended to be earlier than abnormal movements. Nearly half (48%) of those with any seizures, reported they were no longer having recurrent seizures. No single most effective medication for movement disorders or epilepsy was noted. Ten participants have had deep brain stimulator for their movement disorder, and all indicated positive effects. CONCLUSIONS: GNAO1-related neurodevelopmental disorders most often present within the first year of life with nonspecific symptoms of hypotonia or developmental delay. Although associated epilepsy and movement disorders can be severe, GNAO1-associated epilepsy may not always be medically refractory or lifelong.

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3. Barthelson K, Baer L, Dong Y, Hand M, Pujic Z, Newman M, Goodhill GJ, Richards RI, Pederson SM, Lardelli M. Zebrafish Chromosome 14 Gene Differential Expression in the fmr1 (h u2787) Model of Fragile X Syndrome. Frontiers in genetics. 2021; 12: 625466.

Zebrafish represent a valuable model for investigating the molecular and cellular basis of Fragile X syndrome (FXS). Reduced expression of the zebrafish FMR1 orthologous gene, fmr1, causes developmental and behavioural phenotypes related to FXS. Zebrafish homozygous for the hu2787 non-sense mutation allele of fmr1 are widely used to model FXS, although FXS-relevant phenotypes seen from morpholino antisense oligonucleotide (morpholino) suppression of fmr1 transcript translation were not observed when hu2787 was first described. The subsequent discovery of transcriptional adaptation (a form of genetic compensation), whereby mutations causing non-sense-mediated decay of transcripts can drive compensatory upregulation of homologous transcripts independent of protein feedback loops, suggested an explanation for the differences reported. We examined the whole-embryo transcriptome effects of homozygosity for fmr1 (h u2787) at 2 days post fertilisation. We observed statistically significant changes in expression of a number of gene transcripts, but none from genes showing sequence homology to fmr1. Enrichment testing of differentially expressed genes implied effects on lysosome function and glycosphingolipid biosynthesis. The majority of the differentially expressed genes are located, like fmr1, on Chromosome 14. Quantitative PCR tests did not support that this was artefactual due to changes in relative chromosome abundance. Enrichment testing of the « leading edge » differentially expressed genes from Chromosome 14 revealed that their co-location on this chromosome may be associated with roles in brain development and function. The differential expression of functionally related genes due to mutation of fmr1, and located on the same chromosome as fmr1, is consistent with R.A. Fisher’s assertion that the selective advantage of co-segregation of particular combinations of alleles of genes will favour, during evolution, chromosomal rearrangements that place them in linkage disequilibrium on the same chromosome. However, we cannot exclude that the apparent differential expression of genes on Chromosome 14 genes was, (if only in part), caused by differences between the expression of alleles of genes unrelated to the effects of the fmr1 (h u2787) mutation and made manifest due to the limited, but non-zero, allelic diversity between the genotypes compared.

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4. Cleaton MAM, Tal-Saban M, Hill EL, Kirby A. Gender and age differences in the presentation of at-risk or probable Developmental Coordination Disorder in adults. Research in developmental disabilities. 2021; 115: 104010.

BACKGROUND: Developmental Coordination Disorder (DCD), also called Dyspraxia, is a common Neurodevelopmental Disorder (NDD) that affects motor coordination with a marked impact on both academic and day-to-day living activities. It is increasingly clear that NDDs such as Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder may present differently in males and females, resulting in underdiagnoses of women and girls. AIMS: To consider age and gender differences in the presentation of at-risk and probable DCD. METHODS AND PROCEDURES: A sample of 1,476 adults aged 16-60 years were surveyed online using the Adult DCD Checklist. OUTCOMES AND RESULTS: Women with at-risk (n = 1 8 6, 1 6. 6 %) or probable DCD (n = 6 4 3, 5 6. 6 %) reported significantly greater gross motor and non-motor difficulties and significantly greater impact on activities and participation, whereas men with at-risk (n = 58,16.3 %) or probable (n = 177,49.9 %), DCD reported significantly greater fine motor difficulties. Emerging adults (aged 16-25 years) with at-risk (n = 65,14.3 %) or probable (293,64.3 %) DCD reported significantly greater non-motor difficulty than adults (aged 26-60+ years) with at-risk (n = 179,17.5 %) or probable (n = 518, 50.8 %) DCD. CONCLUSIONS AND IMPLICATIONS: Both age and gender differences were found in the presentation of at-risk and probable DCD in adults. This may have implications for the development of future DCD assessment tools and for the training of front-line staff who may encounter individuals with DCD throughout their lives, including teachers, doctors and employers’ Human Resources and Occupational Health staff.

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5. Frei JA, Niescier RF, Bridi MS, Durens M, Nestor JE, Kilander MBC, Yuan X, Dykxhoorn DM, Nestor MW, Huang S, Blatt GJ, Lin YC. Regulation of Neural Circuit Development by Cadherin-11 Provides Implications for Autism. eNeuro. 2021; 8(4).

Autism spectrum disorder (ASD) is a neurologic condition characterized by alterations in social interaction and communication, and restricted and/or repetitive behaviors. The classical Type II cadherins cadherin-8 (Cdh8, CDH8) and cadherin-11 (Cdh11, CDH11) have been implicated as autism risk gene candidates. To explore the role of cadherins in the etiology of autism, we investigated their expression patterns during mouse brain development and in autism-specific human tissue. In mice, expression of cadherin-8 and cadherin-11 was developmentally regulated and enriched in the cortex, hippocampus, and thalamus/striatum during the peak of dendrite formation and synaptogenesis. Both cadherins were expressed in synaptic compartments but only cadherin-8 associated with the excitatory synaptic marker neuroligin-1. Induced pluripotent stem cell (iPSC)-derived cortical neural precursor cells (NPCs) and cortical organoids generated from individuals with autism showed upregulated CDH8 expression levels, but downregulated CDH11. We used Cdh11 knock-out (KO) mice of both sexes to analyze the function of cadherin-11, which could help explain phenotypes observed in autism. Cdh11 (-/-) hippocampal neurons exhibited increased dendritic complexity along with altered neuronal and synaptic activity. Similar to the expression profiles in human tissue, levels of cadherin-8 were significantly elevated in Cdh11 KO brains. Additionally, excitatory synaptic markers neuroligin-1 and postsynaptic density (PSD)-95 were both increased. Together, these results strongly suggest that cadherin-11 is involved in regulating the development of neuronal circuitry and that alterations in the expression levels of cadherin-11 may contribute to the etiology of autism.

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6. Goldberg EM, Tzingounis AV. Towards Targeted Therapy for Neurodevelopmental Disorders Symposium. Developmental neuroscience. 2021; 43(3-4): 141-2.

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7. Kim SK, Liu X, Park J, Um D, Kilaru G, Chiang CM, Kang M, Huber KM, Kang K, Kim TK. Functional coordination of BET family proteins underlies altered transcription associated with memory impairment in fragile X syndrome. Science advances. 2021; 7(21).

Bromodomain and extraterminal proteins (BET) are epigenetic readers that play critical roles in gene regulation. Pharmacologic inhibition of the bromodomain present in all BET family members is a promising therapeutic strategy for various diseases, but its impact on individual family members has not been well understood. Using a transcriptional induction paradigm in neurons, we have systematically demonstrated that three major BET family proteins (BRD2/3/4) participated in transcription with different recruitment kinetics, interdependency, and sensitivity to a bromodomain inhibitor, JQ1. In a mouse model of fragile X syndrome (FXS), BRD2/3 and BRD4 showed oppositely altered expression and chromatin binding, correlating with transcriptional dysregulation. Acute inhibition of CBP/p300 histone acetyltransferase (HAT) activity restored the altered binding patterns of BRD2 and BRD4 and rescued memory impairment in FXS. Our study emphasizes the importance of understanding the BET coordination controlled by a balanced action between HATs with different substrate specificity.

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8. Kissine M, Bertels J, Deconinck N, Passeri G, Deliens G. Audio-visual integration in nonverbal or minimally verbal young autistic children. Journal of experimental psychology General. 2021; 150(10): 2137-57.

Low integration of speech sounds with the mouth movements likely contributes to language acquisition disabilities that frequently characterize young autistic children. However, the existing empirical evidence either relies on complex verbal instructions or merely focuses on preferential gaze on in-synch videos. The former method is clearly unadapted for young, minimally, or nonverbal autistic children, while the latter has several biases, making it difficult to interpret the data. We designed a Reinforced Preferential Gaze paradigm that allows to test multimodal integration in young, nonverbal autistic children and overcomes several of the methodological challenges faced by previous studies. We show that autistic children have difficulties in temporally binding the speech signal with the corresponding articulatory gestures. A condition with structurally similar nonsocial video stimuli suggests that atypical multimodal integration in autism is not limited to speech stimuli. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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9. Lee CM, Bo J. Visuomotor adaptation and its relationship with motor ability in children with and without autism spectrum disorder. Human movement science. 2021; 78: 102826.

The high prevalence rates of motor impairments among individuals with autism spectrum disorder (ASD) lead to increased attention to motor learning. The current study examined the visuomotor adaptability in children with and without ASD using a computerized visuomotor adaptation task in which the real-time visual feedback of hand movement was rotated. The relationships between visuomotor adaptability and clinical symptomology were also investigated. Results revealed that the children with ASD showed a slower rate of improvement and smaller after-effects than their peers on the measures of motor planning. Additionally, autistic characteristics significantly moderated the association between individuals’ adaptability and fine motor skills. The findings contribute to the growing evidence of compromised visuomotor adaptability, which suggested the importance of addressing these clinical features of ASD.

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10. Muris P, Monait N, Weijsters L, Ollendick TH. Symptoms of Selective Mutism in Non-clinical 3- to 6-Year-Old Children: Relations With Social Anxiety, Autistic Features, and Behavioral Inhibition. Frontiers in psychology. 2021; 12: 669907.

Selective mutism (SM) is a psychiatric condition that is characterized by a failure to speak in specific social situations (e. g., at school) despite speaking normally in other situations (e.g., at home). There is abundant evidence that anxiety, and social anxiety in particular, is a prominent feature of SM, which is the main reason why this condition is currently classified as an anxiety disorder. Meanwhile, there is increasing support for the notion that autism-related problems are also involved in SM. The present study examined the relations between SM and social anxiety, autistic features, and behavioral inhibition to the unfamiliar (i.e., the tendency to react with restraint and withdrawal when confronted with unfamiliar stimuli and situations). Parents of 172 3- to 6-year-old preschool children completed an online survey for measuring the relevant constructs. Results showed that there were positive and statistically significant correlations between SM and social anxiety, autistic features, and behavioral inhibition. Regression analyses revealed that (1) both social anxiety and autistic features accounted for a significant and unique proportion of the variance in SM scores, and (2) that both of these variables no longer made a significant contribution once behavioral inhibition was added to the model. It can be concluded that while the involvement of social anxiety is unambiguous in SM, autism-related problems are also implicated. Furthermore, behavioral inhibition seems to play a key role in the non-speaking behavior of non-clinical young children.

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11. Nelson AD, Bender KJ. Dendritic Integration Dysfunction in Neurodevelopmental Disorders. Developmental neuroscience. 2021; 43(3-4): 201-21.

Neurodevelopmental disorders (NDDs) that affect cognition, social interaction, and learning, including autism spectrum disorder (ASD) and intellectual disability (ID), have a strong genetic component. Our current understanding of risk genes highlights two main groups of dysfunction: those in genes that act as chromatin modifiers and those in genes that encode for proteins localized at or near synapses. Understanding how dysfunction in these genes contributes to phenotypes observed in ASD and ID remains a major question in neuroscience. In this review, we highlight emerging evidence suggesting that dysfunction in dendrites – regions of neurons that receive synaptic input – may be key to understanding features of neuronal processing affected in these disorders. Dendritic integration plays a fundamental role in sensory processing, cognition, and conscious perception, processes hypothesized to be impaired in NDDs. Many high-confidence ASD genes function within dendrites where they control synaptic integration and dendritic excitability. Further, increasing evidence demonstrates that several ASD/ID genes, including chromatin modifiers and transcription factors, regulate the expression or scaffolding of dendritic ion channels, receptors, and synaptic proteins. Therefore, we discuss how dysfunction of subsets of NDD-associated genes in dendrites leads to defects in dendritic integration and excitability and may be one core phenotype in ASD and ID.

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12. Pomper R, Ellis Weismer S, Saffran J, Edwards J. Coarticulation facilitates lexical processing for toddlers with autism. Cognition. 2021; 214: 104799.

Many children with autism spectrum disorder (ASD) are delayed in learning language. The mechanisms underlying these delays are not well understood but may involve differences in how children process language. In the current experiment, we compared how 3- to 4-year-old children with ASD (n = 58) and 2- to 3-year-old children who are typically developing (TD, n = 44) use phonological information to incrementally process speech. Children saw pictures of objects displayed on a screen and heard sentences labeling one of the objects (e.g., Find the ball). For some sentences, the determiner the contained coarticulatory information about the onset of the target word. For other sentences, the determiner the did not contain any coarticulatory information. Children were faster to fixate the target object for sentences with vs. without coarticulation. This effect of coarticulation was the same for children with ASD compared to their TD peers. When controlling for group differences in receptive language ability, the effect of coarticulation was stronger for children with ASD compared to their TD peers. These results suggest that phonological processing is an area of relative strength for children with ASD.

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13. Pondé MP, Wanderley DB, Menezes LD, Gomes FL, Siquara GM. A validation study of the LABIRINTO scale for the evaluation of autism spectrum disorder in children aged 2 to 4 years. Trends in psychiatry and psychotherapy. 2021; 43(4): 320-8.

OBJECTIVE: To find evidence of the content, construct, and criterion validity of the LABIRINTO scale for the diagnosis of autism spectrum disorder (ASD) in children aged 24-59 months. METHODS: The scale was constructed in four stages: 1) items were defined based on an extensive literature review and discussions with autism and child development specialists; 2) child development specialists evaluated each item; 3) a preliminary version of the scale was applied to children diagnosed with ASD to enable any necessary adjustments; 4) the scale was then applied to 27 children with typical development and no neurodevelopmental disorder and 48 children with ASD. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the Childhood Autism Rating Scale (CARS), clinical diagnosis constitutes the gold standard. RESULTS: The scale’s psychometric indexes were appropriate for construct validity, with Kaiser-Meyer-Olkin = 0.94 and root mean square error of approximation = 0.000. Only one factor on the scale had a Cronbach alpha of 0.97. The receiver operating characteristic curve indicated a cutoff of 12, with a sensitivity of 100% and specificity of 100% for distinguishing children with ASD from those with typical development. CONCLUSION: This study confirmed the validity of the LABIRINTO scale.

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14. Rajendram R, Psihogios M, Toulany A. Delayed diagnosis of avoidant/restrictive food intake disorder and autism spectrum disorder in a 14-year-old boy. Clinical case reports. 2021; 9(6): e04302.

Psychiatric comorbidities are common among individuals with ARFID and may contribute to a failure to establish an accurate diagnosis, delayed diagnosis, and poor long-term prognosis, especially among children and adolescents.

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15. Raouf S, Kodsi S, Schwartzstein H, Hymowitz M, Black K, Pomeranz HD. Bilateral optic nerve compression secondary to skull hyperostosis from vitamin A deficiency. Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus. 2021; 25(4): 245-7.

A 15-year-old boy with a history of autism spectrum disorder presented with bilateral progressive blurry vision and nyctalopia. Initial examinations, including optical coherence tomography scans of the macula and optic nerve, were within normal limits. Subsequent examination revealed trace pallor of the right optic nerve. Computed tomography and magnetic resonance imaging of the brain demonstrated diffuse thickening of calvarial bone with bilateral optic nerve compression. Laboratory evaluation was notable for profound vitamin A deficiency. The patient underwent optic nerve decompression and vitamin A supplementation with postoperative improvement in visual acuity of both eyes.

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16. Skorich DP, Cassidy LM, Karimi KS, Haslam SA. Self-categorization and autism: Exploring the relationship between autistic traits and group homogeneity. Journal of experimental psychology Applied. 2021.

The Integrated Self-Categorization model of Autism (ISCA; Bertschy et al., 2019; Skorich & Haslam, 2021) argues that the theory of mind differences seen in autism arises from Enhanced Perceptual Functioning/Weak Central Coherence, via a dysfunctional self-categorization mechanism. The ISCA model also makes the novel prediction that phenomena that arise from self-categorization should also be affected in autistic people. In this article, we report three studies exploring this prediction in the context of one such phenomenon: Group homogeneity. We first measure participants’ autistic traits, then ask them to make homogeneity judgments of their ingroup alone or their outgroup alone (in Study 1, and in the Alone conditions of Studies 2a and 2b); or of their ingroup in comparison to their outgroup or their outgroup in comparison to their ingroup (in the Compare conditions of Studies 2a and 2b). As predicted, we find that: the degree of autistic traits negatively predicts ratings of group homogeneity; this relationship is mediated by social identification/self-categorization; and typical comparison-related homogeneity effects are strengthened at higher relative to lower levels of autistic traits. These studies provide convergent evidence for the ISCA model and suggest important avenues for well-being and social skills interventions for autistic people. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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17. Zimmerman AW, Singh K, Connors SL, Liu H, Panjwani AA, Lee LC, Diggins E, Foley A, Melnyk S, Singh IN, Jill James S, Frye RE, Fahey JW. Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder. Molecular autism. 2021; 12(1): 44.

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