1. Ali SG, Wang X, Li P, Jung Y, Bi L, Kim J, Chen Y, Feng DD, Magnenat Thalmann N, Wang J, Sheng B. A systematic review: Virtual-reality-based techniques for human exercises and health improvement. Frontiers in public health. 2023; 11: 1143947.

Virtual Reality (VR) has emerged as a new safe and efficient tool for the rehabilitation of many childhood and adulthood illnesses. VR-based therapies have the potential to improve both motor and functional skills in a wide range of age groups through cortical reorganization and the activation of various neuronal connections. Recently, the potential for using serious VR-based games that combine perceptual learning and dichoptic stimulation has been explored for the rehabilitation of ophthalmological and neurological disorders. In ophthalmology, several clinical studies have demonstrated the ability to use VR training to enhance stereopsis, contrast sensitivity, and visual acuity. The use of VR technology provides a significant advantage in training each eye individually without requiring occlusion or penalty. In neurological disorders, the majority of patients undergo recurrent episodes (relapses) of neurological impairment, however, in a few cases (60-80%), the illness progresses over time and becomes chronic, consequential in cumulated motor disability and cognitive deficits. Current research on memory restoration has been spurred by theories about brain plasticity and findings concerning the nervous system’s capacity to reconstruct cellular synapses as a result of interaction with enriched environments. Therefore, the use of VR training can play an important role in the improvement of cognitive function and motor disability. Although there are several reviews in the community employing relevant Artificial Intelligence in healthcare, VR has not yet been thoroughly examined in this regard. In this systematic review, we examine the key ideas of VR-based training for prevention and control measurements in ocular diseases such as Myopia, Amblyopia, Presbyopia, and Age-related Macular Degeneration (AMD), and neurological disorders such as Alzheimer, Multiple Sclerosis (MS) Epilepsy and Autism spectrum disorder. This review highlights the fundamentals of VR technologies regarding their clinical research in healthcare. Moreover, these findings will raise community awareness of using VR training and help researchers to learn new techniques to prevent and cure different diseases. We further discuss the current challenges of using VR devices, as well as the future prospects of human training.

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2. Anbar J, Matthews N, James S, Ariff A, Pierce K, Smith CJ. Examination of Clinical and Assessment Type Differences Between Toddlers with ASD from Multiplex and Simplex Families. Journal of autism and developmental disorders. 2023.

Few studies have examined differences in autism spectrum disorder (ASD) phenotype between children from multiplex and simplex families at the time of diagnosis. The present study used an age- and gender-matched, community-based sample (n = 105) from the southwestern United States to examine differences in ASD symptom severity, cognitive development, and adaptive functioning. No significant differences between children from multiplex and simplex families were observed. Exploratory analysis revealed that parents underreported receptive and expressive language and fine motor skills compared to professional observation, especially among children from multiplex families. These findings suggest that diagnosticians may need to consider family structure when choosing and interpreting assessments of receptive language, expressive language, and fine motor skills.

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3. Badia M, Pérez B, Orgaz BM, Gómez-Vela M. Leisure education in youth with developmental disabilities: Effects on individual quality of life, adaptive behavior, and family quality of life. Journal of intellectual disabilities : JOID. 2023: 17446295231168442.

Leisure participation enhances the learning of adaptive skills and the quality of life in youth with developmental disabilities. The goal of this study was to evaluate the effects of a leisure education program in individuals with developmental disabilities in terms of adaptive behavior and quality of life. Nine participants divided into two small groups and their families were included. A quasi-experimental design was employed to determine whether there was a program effect. The Adaptive Behavior Assessment System, the KIDSCREEN-27, and the Family Quality of Life Scale were administered before and after the intervention. There was a significant increase in social, home, and school skills as well as a better perception of quality of life in relationships with parents, social support, and school. In addition, the program affected the family’s perception of practical and emotional support. Findings provide support for the application of this leisure program to enhance quality of life outcomes.

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4. Bagnall R, Cadman A, Russell A, Brosnan M, Otte M, Maras KL. Police suspect interviews with autistic adults: The impact of truth telling versus deception on testimony. Frontiers in psychology. 2023; 14: 1117415.

Investigative interviews by police are socially and cognitively demanding encounters, likely presenting significant challenges to those on the autism spectrum. Behavioral and communication differences mean that autistic people may also be more likely to be perceived as deceptive in the context of an investigative interview. In the present study, 32 autistic and 33 (age and IQ-matched) non-autistic adults took part in a novel virtual burglary scenario in either an ‘innocent’ or ‘guilty’ condition. In a subsequent mock-police interview, innocent suspects were instructed to tell the truth about what they did, while guilty suspects were instructed to lie in order to convince the interviewer of their innocence. In the mock-interviews, innocent autistic mock-suspects reported fewer details that would support their innocence than non-autistic mock-suspects, although both innocent and guilty autistic and non-autistic mock-suspects reported similar levels of investigation-relevant information and had similar levels of statement-evidence consistency. In post-interview questionnaires, innocent and guilty autistic mock-suspects self-reported greater difficulty in understanding interview questions, higher anxiety and perceived the interview as less supportive than non-autistic participants. Implications for investigative interviewing with autistic suspects and cues to deception are discussed.

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5. Che X, Roy A, Bresnahan M, Mjaaland S, Reichborn-Kjennerud T, Magnus P, Stoltenberg C, Shang Y, Zhang K, Susser E, Fiehn O, Lipkin WI. Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders. Molecular psychiatry. 2023.

The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17-21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.

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6. Chung S, Son JW. How Well Do We Understand Autistic Savant Artists: A Review of Various Hypotheses and Research Findings to Date. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(2): 93-111.

The authors investigated the artistic characteristics of autistic savant artists, hypotheses on the proximate and ultimate causes of their emergence, recent psychological and other studies about them, and psychological and neuroaesthetic studies about non-savant autistic individuals. The artistic features of autistic savant artists were significantly similar to those of outsider artists. Furthermore, the authors investigated the explanatory power of the paradoxical functional facilitation theory, the superior visual perception hypothesis, the « Hmmmmm » hypothesis, and the Neanderthal theory of autism regarding the emergence of autistic savant artists. In addition, we investigated whether an increase in savant characteristics was related to a decrease in the ability for social communication. The authors suggested that in studies on the aesthetic experience of non-savant autistic individuals, their aesthetic experience ability is never lower than that of neurotypical individuals and that some non-savant autistic individuals may potentially have artistic talent. Finally, the authors reviewed the effectiveness of the « autism savant spectrum syndromic disorder » proposed by some researchers. More scientific and systematic studies on autistic savant artists from a multidisciplinary perspective are warranted.

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7. Dufault RJ, Crider RA, Deth RC, Schnoll R, Gilbert SG, Lukiw WJ, Hitt AL. Higher rates of autism and attention deficit/hyperactivity disorder in American children: Are food quality issues impacting epigenetic inheritance?. World journal of clinical pediatrics. 2023; 12(2): 25-37.

In the United States, schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals. Pediatricians may play a key role in helping children access special education services. The number of children ages 6-21 in the United States receiving special education services increased 10.4% from 2006 to 2021. Children receiving special education services under the autism category increased 242% during the same period. The demand for special education services for children under the developmental delay and other health impaired categories increased by 184% and 83% respectively. Although student enrollment in American schools has remained stable since 2006, the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021. Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes. Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics. Dietary heavy metal exposures, especially inorganic mercury and lead may impact gene behavior across generations. In 2021, the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action. Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.

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8. Elamin M, Dumarchey A, Stoddard C, Robinson TM, Cowie C, Gorka D, Chamberlain SJ, Levine ES. The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons. Stem cell reports. 2023; 18(4): 884-98.

Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features of Dup15q. UBE3A, which encodes an E3 ubiquitin ligase, is likely a major driver of Dup15q because UBE3A is the only imprinted gene expressed solely from the maternal allele. Nevertheless, the exact role of UBE3A has not been determined. To establish whether UBE3A overexpression is required for Dup15q neuronal deficits, we generated an isogenic control line for a Dup15q patient-derived induced pluripotent stem cell line. Dup15q neurons exhibited hyperexcitability compared with control neurons, and this phenotype was generally prevented by normalizing UBE3A levels using antisense oligonucleotides. Overexpression of UBE3A resulted in a profile similar to that of Dup15q neurons except for synaptic phenotypes. These results indicate that UBE3A overexpression is necessary for most Dup15q cellular phenotypes but also suggest a role for other genes in the duplicated region.

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9. Esquilín Nieves AA, Danzak RL. Examining Perspectives of Latina Mothers and Speech-Language Pathologists Through Dyadic Interviews: Implications for Latine Children on the Autism Spectrum. Language, speech, and hearing services in schools. 2023: 1-19.

PURPOSE: This qualitative pilot study explored cultural perspectives and needs of two bilingual (Spanish/English) Latina mothers with children on the autism spectrum in conversations with their children’s speech-language pathologists (SLPs), one identifying as Mexican American and the other identifying as White American. METHOD: Dyadic interviews were used to promote dialogue and learning opportunities for the participants. Two dyads (mothers and SLPs) participated, completing background questionnaires, dyadic interviews, and post-interview written reflections. RESULTS: Three main themes emerged from the qualitative analysis of the dyadic interviews: comunicación (communication), language, and challenge. Post-interview written reflections evidenced increased advocacy skills for the mothers and heightened awareness regarding communication style for the SLPs. CONCLUSION: The lived experiences revealed by all participants offer several implications: (a) the value of extended conversations between caregivers and service providers, (b) caregiver sacrifices, (c) the importance of cultural sensitivity for SLPs, and (d) positive outcomes from online learning for children on the autism spectrum.

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10. Gredell M, Lu J, Zuo Y. The effect of single-cell knockout of Fragile X Messenger Ribonucleoprotein on synaptic structural plasticity. Frontiers in synaptic neuroscience. 2023; 15: 1135479.

Fragile X Syndrome (FXS) is the best-known form of inherited intellectual disability caused by the loss-of-function mutation in a single gene. The FMR1 gene mutation abolishes the expression of Fragile X Messenger Ribonucleoprotein (FMRP), which regulates the expression of many synaptic proteins. Cortical pyramidal neurons in postmortem FXS patient brains show abnormally high density and immature morphology of dendritic spines; this phenotype is replicated in the Fmr1 knockout (KO) mouse. While FMRP is well-positioned in the dendrite to regulate synaptic plasticity, intriguing in vitro and in vivo data show that wild type neurons embedded in a network of Fmr1 KO neurons or glia exhibit spine abnormalities just as neurons in Fmr1 global KO mice. This raises the question: does FMRP regulate synaptic morphology and dynamics in a cell-autonomous manner, or do the synaptic phenotypes arise from abnormal pre-synaptic inputs? To address this question, we combined viral and mouse genetic approaches to delete FMRP from a very sparse subset of cortical layer 5 pyramidal neurons (L5 PyrNs) either during early postnatal development or in adulthood. We then followed the structural dynamics of dendritic spines on these Fmr1 KO neurons by in vivo two-photon microscopy. We found that, while L5 PyrNs in adult Fmr1 global KO mice have abnormally high density of thin spines, single-cell Fmr1 KO in adulthood does not affect spine density, morphology, or dynamics. On the contrary, neurons with neonatal FMRP deletion have normal spine density but elevated spine formation at 1 month of age, replicating the phenotype in Fmr1 global KO mice. Interestingly, these neurons exhibit elevated thin spine density, but normal total spine density, by adulthood. Together, our data reveal cell-autonomous FMRP regulation of cortical synaptic dynamics during adolescence, but spine defects in adulthood also implicate non-cell-autonomous factors.

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11. Hageman JR, Alcocer Alkureishi L. Developmental Disabilities Awareness. Pediatric annals. 2023; 52(4): e122-e3.

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12. Harris E. Trofinetide Receives FDA Approval as First Drug for Rett Syndrome. Jama. 2023; 329(14): 1142.

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13. He JL, Williams ZJ, Harris A, Powell H, Schaaf R, Tavassoli T, Puts NAJ. A working taxonomy for describing the sensory differences of autism. Molecular autism. 2023; 14(1): 15.

BACKGROUND: Individuals on the autism spectrum have been long described to process sensory information differently than neurotypical individuals. While much effort has been leveraged towards characterizing and investigating the neurobiology underlying the sensory differences of autism, there has been a notable lack of consistency in the terms being used to describe the nature of those differences. MAIN BODY: We argue that inconsistent and interchangeable terminology-use when describing the sensory differences of autism has become problematic beyond mere pedantry and inconvenience. We begin by highlighting popular terms that are currently being used to describe the sensory differences of autism (e.g. « sensitivity », « reactivity » and « responsivity ») and discuss why poor nomenclature may hamper efforts towards understanding the aetiology of sensory differences in autism. We then provide a solution to poor terminology-use by proposing a hierarchical taxonomy for describing and referring to various sensory features. CONCLUSION: Inconsistent terminology-use when describing the sensory features of autism has stifled discussion and scientific understanding of the sensory differences of autism. The hierarchical taxonomy proposed was developed to help resolve lack of clarity when discussing the sensory differences of autism and to place future research targets at appropriate levels of analysis.

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14. Hidaka S, Gotoh M, Yamamoto S, Wada M. Exploring relationships between autistic traits and body temperature, circadian rhythms, and age. Scientific reports. 2023; 13(1): 5888.

The number of clinical diagnoses of autism spectrum disorder (ASD) is increasing annually. Interestingly, the human body temperature has also been reported to gradually decrease over the decades. An imbalance in the activation of the excitatory and inhibitory neurons is assumed to be involved in the pathogenesis of ASD. Neurophysiological evidence showed that brain activity decreases as cortical temperature increases, suggesting that an increase in brain temperature enhances the inhibitory neural mechanisms. Behavioral characteristics specific to clinical ASD were observed to be moderated when people with the diagnoses had a fever. To explore the possible relationship between ASD and body temperature in the general population, we conducted a survey study using a large population-based sample (N ~ 2000, in the age groups 20s to 70s). Through two surveys, multiple regression analyses did not show significant relationships between axillary temperatures and autistic traits measured by questionnaires (Autism Spectrum (AQ) and Empathy/Systemizing Quotients), controlling for covariates of age and self-reported circadian rhythms. Conversely, we consistently observed a negative relationship between AQ and age. People with higher AQ scores tended to have stronger eveningness. Our findings contribute to the understanding of age-related malleability and the irregularity of circadian rhythms related to autistic traits.

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15. Hwang JW. How Are Autism Spectrum Disorder and Savant Skills Treated in Cinematographic Works? A Study Focusing on Korean Movies and TV Series. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(2): 112-6.

Numerous films and TV series worldwide have depicted characters with autism spectrum disorder (ASD) and savant skills. This study describes the portrayal of ASD and savant skills in Korean films and dramas. Starting with the 2005 film Marathon, characters with ASD have been featured in five films and four dramas. Most portrayals were based on the diagnostic criteria and pathogenesis of ASD, as outlined in the DSM-5. Of the 10 characters with ASD in these films and dramas, seven were male and three were female, with seven of them possessing savant skills. In the future, caution and guidance on the general characteristics of ASD from experts should be provided with the release of ASD-based films and TV dramas in Korea; in addition, critiques and social discourse pertinent to the reality of ASD should be provided by people with ASD, their families, and relevant experts.

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16. Itahashi T, Yamashita A, Takahara Y, Yahata N, Aoki YY, Fujino J, Yoshihara Y, Nakamura M, Aoki R, Ohta H, Sakai Y, Takamura M, Ichikawa N, Okada G, Okada N, Kasai K, Tanaka SC, Imamizu H, Kato N, Okamoto Y, Takahashi H, Kawato M, Yamashita O, Hashimoto RI. Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study. bioRxiv : the preprint server for biology. 2023.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; all P <0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

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17. Khandan Khadem-Reza Z, Shahram MA, Zare H. Altered resting-state functional connectivity of the brain in children with autism spectrum disorder. Radiological physics and technology. 2023.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders. Brain mapping has shown that functional brain connections are altered in autism. This study investigated the pattern of brain connection changes in autistic people compared to healthy people. This study aimed to analyze functional abnormalities within the brain due to ASD, using resting-state functional magnetic resonance imaging (fMRI). Resting-state functional magnetic resonance images of 26 individuals with ASD and 26 healthy controls were obtained from the Autism Brain Imaging Data Exchange (ABIDE) database. The DPARSF (data processing assistant for resting-state fMRI) toolbox was used for resting-state functional image processing, and features related to functional connections were extracted from these images. Then, the extracted features from both groups were compared using an Independent Two-Sample T Test, and the features with significant differences between the two groups were identified. Compared with healthy controls, individuals with ASD showed hyper-connectivity in the frontal lobe, anterior cingulum, parahippocampal, left precuneus, angular, caudate, superior temporal, and left pallidum, as well as hypo-connectivity in the precentral, left superior frontal, left middle orbitofrontal, right amygdala, and left posterior cingulum. Our findings show that abnormal functional connectivity exists in patients with ASD. This study makes an important advancement in our understanding of the abnormal neurocircuits causing autism.

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18. Klein J, Kerns C, Hills K, Hogan A, Matherly S, Roberts J. Brief Report: Prevalence and Predictors of DSM-Specific and Distinct Anxiety in Cognitively Impaired Autistic Preschool Children. Journal of autism and developmental disorders. 2023.

Autistic individuals are twice as likely to meet criteria for anxiety than neurotypical children; yet we lack understanding of early presentations of anxiety in young autistic children, especially those with cognitive impairment. This study is the first to utilize an autism-specific anxiety diagnostic interview with 28 preschool cognitively impaired, autistic children and 18 neurotypical, age-matched controls. Results indicate that 64% of autistic children met criteria for DSM-specified or « other specified, » herein referred to as « distinct, » anxiety disorders; 32% met criteria for multiple anxiety disorders, with phobias occurring most often. Results indicate that anxiety is highly prevalent in cognitively-impaired, autistic preschool children, highlighting the need for developmentally-tailored assessment and treatment in early childhood.

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19. McGlade A, Whittingham K, Barfoot J, Taylor L, Boyd RN. Efficacy of very early interventions on neurodevelopmental outcomes for infants and toddlers at increased likelihood of or diagnosed with autism: A systematic review and meta-analysis. Autism research : official journal of the International Society for Autism Research. 2023.

The aim of this systematic review was to determine the efficacy of very early interventions for infants and toddlers at increased likelihood of or diagnosed with autism for autism symptomatology, developmental outcomes and/or neurocognitive markers. Eight databases were searched (14 April 2022) with inclusion criteria: (i) RCTs with care as usual (CAU) comparison group, (ii) participants at increased likelihood of or diagnosed with autism and aged <24 months corrected age (CA), (iii) parent-mediated and/or clinician directed interventions, and (iv) outcome measures were autism symptomatology, cognition, language, adaptive skills, or neurocognitive assessments (EEG and eye tracking). Quality was assessed using Risk of Bias 2 and GRADE. Nineteen publications from 12 studies reported on 715 infants and toddlers. There was low to moderate certainty evidence that clinician-assessed outcomes did not show significant treatment effects for: autism symptomatology (ADOS CSS: MD -0.08, 95% CI -0.61, 0.44, p = 0.75), cognitive outcome (Mullen Scales of Early Learning-Early Learning Composite (MSEL-ELC): SMD 0.05, 95% CI -0.19, 0.29, p = 0.67), receptive language (MSEL-Receptive Language: SMD 0.04, 95% CI -0.21, 0.3, p = 0.74) or expressive language (MSEL-Expressive Language: SMD 0.06, 95% CI -0.1, 0.23, p = 0.45). Neurocognitive outcomes (EEG and eye tracking) were heterogeneous, with inconsistent findings. There is low to moderate certainty evidence that very early interventions have limited impact on neurodevelopmental outcomes by age 3 years.

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20. Navarro-Pardo E, Alonso-Esteban Y, Alcantud-Marin F, Murphy M. Do Savant Syndrome and Autism Spectrum Disorders Share Sex Differences? A Comprehensive Review. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(2): 117-24.

Savant syndrome was described before autism. However, they soon became closely associated, as many of their symptoms (intellectual disability, repetitive behaviors, alterations in social communication, and islets of abilities) overlap. Only a few women with autism have been diagnosed with savant syndrome. The theories or hypotheses that attempt to explain savant syndrome, which are common in autism, present differential treatment according to sex. We postulate that savant syndrome associated with autism as well as autism in general is underdiagnosed in women.

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21. Novotný A, Plavec J, Kocman V. Structural polymorphism driven by a register shift in a CGAG-rich region found in the promoter of the neurodevelopmental regulator AUTS2 gene. Nucleic acids research. 2023; 51(6): 2602-13.

The AUTS2 gene has been shown to influence brain development by controlling the number of neurons, promoting the growth of axons and dendrites and regulating neuronal migration. The expression of two isoforms of AUTS2 protein is precisely regulated and misregulation of their expression has been correlated with neurodevelopmental delay and autism spectrum disorder. A CGAG-rich region, which includes a putative protein binding site (PPBS), d(AGCGAAAGCACGAA), was found in the promoter region of AUTS2 gene. We show that oligonucleotides from this region adopt thermally stable non-canonical hairpin structures stabilized by G:C and sheared G:A base pairs arranged in a repeating structural motif we termed CGAG block. These motifs are formed consecutively, in a way that exploits a shift in register throughout the whole CGAG repeat to maximize the number of consecutive G:C and G:A base pairs. The differences in CGAG repeat shifting affect the structure of the loop region, where PPBS residues are predominantly located, specifically the loop length, types of base pairs and the pattern of base-base stacking. Finally, we propose a previously unexplored mechanism, by which different folds in the CGAG-rich region could cause a switch in expression between the full-length and C-terminal isoforms of AUTS2.

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22. Oomen D, Cracco E, Brass M, Wiersema JR. EEG frequency tagging evidence of intact social interaction recognition in adults with autism. Autism research : official journal of the International Society for Autism Research. 2023.

To explain the social difficulties in autism, many studies have been conducted on social stimuli processing. However, this research has mostly used basic social stimuli (e.g., eyes, faces, hands, single agent), not resembling the complexity of what we encounter in our daily social lives and what people with autism experience difficulties with. Third-party social interactions are complex stimuli that we come across often and are also highly relevant for social functioning. Interestingly, the existing behavioral studies point to altered social interaction processing in autism. However, it is not clear whether this is due to altered recognition or altered interpretation of social interactions. Here, we specifically investigated the recognition of social interaction in adults with and without autism. More precisely, we measured neural responses to social scenes depicting either social interaction or not with an electroencephalogram frequency tagging task and compared these responses between adults with and without autism (N = 61). The results revealed an enhanced response to social scenes with interaction, replicating previous findings in a neurotypical sample. Crucially, this effect was found in both groups, with no difference between them. This suggests that social interaction recognition is not atypical in adults with autism. Taken together with the previous behavioral evidence, our study thus suggests that individuals with autism are able to recognize social interactions, but that they might not extract the same information from those interactions or that they might use the extracted information differently.

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23. Ozonoff S, Hill MM, Hill A, Ashley K, Young GS. Factors related to retention in a longitudinal study of infants at familial risk for autism. JCPP advances. 2023; 3(1): e12140.

BACKGROUND: Reporting retention data is critical to determining the soundness of a study’s conclusions (internal validity) and broader generalizability (external validity). Although selective attrition can lead to overestimates of effects, biased conclusions, or overly expansive generalizations, retention rates are not reported in many longitudinal studies. METHODS: We examined multiple child- and family-level factors potentially associated with retention in a longitudinal study of younger siblings of children with autism spectrum disorder (ASD; n = 304) or typical development (n = 163). The sample was followed from the first year of life to 36 months of age, for up to 7 visits. RESULTS: Of the 467 infant siblings who were consented and participated in at least one research visit, 397 (85.0%) were retained to study completion at 36 months. Retention rates did not differ by familial risk group (ASD-risk vs. Low-risk), sex, race, ethnicity, age at enrollment, number of children in the family, maternal employment, marital status, or parent concerns about the child at enrollment. A stepwise regression model identified 4 variables that, together, provided the most parsimonious predictive model of study retention: maternal education, maternal age at child’s birth, travel distance to the study site, and diagnostic outcome classification at the final study visit. CONCLUSIONS: The retained and not-retained groups did not differ on most demographic and clinical variables, suggesting few threats to internal and external validity. The significantly higher rate of retention of children diagnosed with ASD (95%) than typically developing children (83%) may, however, present biases when studying recurrence risk. We conclude by describing engagement and tracking methods that can be used to maximize retention in longitudinal studies of children at risk of ASD.

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24. Park HO. Autism Spectrum Disorder and Savant Syndrome: A Systematic Literature Review. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(2): 76-92.

OBJECTIVES: This study aimed to analyze research trends in autism spectrum disorder (ASD) and savant syndrome and their cognitive characteristics through a systematic literature review. The objectives of this study were to establish an overview of research trends in ASD and savant syndrome, analyze the overall characteristics of individuals with ASD and savant syndrome, and examine their cognitive characteristics. METHODS: For the systematic literature review, three criteria were used to select review articles: 1) literature from peer-reviewed journals, published in the past 15 years, from 2008 to 2022; 2) subjects with ASD and savant syndrome; 3) study objectives focused on the basic phenomenon and cognitive characteristics of ASD and savant syndrome. Finally, based on the selection criteria, a total of 40 articles were included. RESULTS: Five themes and nine subthemes were derived from the analysis of 40 studies. The five main themes were as follows: 1) What is savant syndrome? 2) Demographic characteristics of savant syndrome; 3) Spectra of savant syndrome; 4) Savant syndrome and ASD; and 5) Cognitive characteristics of ASD with savant syndrome. The subthemes of the cognitive characteristics were weak central coherence, detail-focused cognitive processing, enhanced perceptual functioning, and hyper-systemizing. CONCLUSION: Several studies have been conducted to understand ASD and savant syndrome; however, no single theory can specify the cognitive characteristics of people with ASD and savant syndrome. Therefore, further systematic and multi-layered research on ASD and savant syndrome are required for more comprehensive results.

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25. Paul MS, Michener SL, Pan H, Pfliger JM, Rosenfeld JA, Lerma VC, Tran A, Longley MA, Lewis RA, Weisz-Hubshman M, Bekheirnia MR, Bekheirnia N, Massingham L, Zech M, Wagner M, Engels H, Cremer K, Mangold E, Peters S, Trautmann J, Mester JL, Guillen Sacoto MJ, Person R, McDonnell PP, Cohen SR, Lusk L, Cohen ASA, Pichon JL, Pastinen T, Zhou D, Engleman K, Racine C, Faivre L, Moutton S, Pichon AD, Schuhmann S, Vasileiou G, Russ-Hall S, Scheffer IE, Carvill GL, Mefford H, Network UD, Bacino CA, Lee BH, Chao HT. Rare variants in PPFIA3 cause delayed development, intellectual disability, autism, and epilepsy. medRxiv : the preprint server for health sciences. 2023.

PPFIA3 encodes the Protein-Tyrosine Phosphatase, Receptor-Type, F Polypeptide-Interacting Protein Alpha-3 (PPFIA3), which is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family involved in synaptic vesicle transport and presynaptic active zone assembly. The protein structure and function are well conserved in both invertebrates and vertebrates, but human diseases related to PPFIA3 dysfunction are not yet known. Here, we report 14 individuals with rare mono-allelic PPFIA3 variants presenting with features including developmental delay, intellectual disability, hypotonia, autism, and epilepsy. To determine the pathogenicity of PPFIA3 variants in vivo , we generated transgenic fruit flies expressing either human PPFIA3 wildtype (WT) or variant protein using GAL4-UAS targeted gene expression systems. Ubiquitous expression with Actin-GAL4 showed that the PPFIA3 variants had variable penetrance of pupal lethality, eclosion defects, and anatomical leg defects. Neuronal expression with elav-GAL4 showed that the PPFIA3 variants had seizure-like behaviors, motor defects, and bouton loss at the 3 (rd) instar larval neuromuscular junction (NMJ). Altogether, in the fly overexpression assays, we found that the PPFIA3 variants in the N-terminal coiled coil domain exhibited stronger phenotypes compared to those in the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of fly Liprin- α leads to embryonic lethality. This lethality is partially rescued by the expression of human PPFIA3 WT, suggesting human PPFIA3 protein function is partially conserved in the fly. However, the PPFIA3 variants failed to rescue lethality. Altogether, the human and fruit fly data reveal that the rare PPFIA3 variants are dominant negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.

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26. Petretto DR, Lucarelli L, Farris P, Penna V, Valinotti S, Pietro CG, Gaviano L, Berti R, Pili L, Zolo B, Pili R. Children with autism spectrum disorders and severe visual impairments: Some general principles for intervention according to the perspective of clinical psychology of disability. Journal of public health research. 2023; 12(2): 22799036231166314.

In the last decades, an increasing number of researchers addressed the relationship between autism spectrum disorders (ASD) and severe visual impairment (SVI) (like blindness or very low visual acuity) and nowadays autism could be considered one of the most reported coexisting developmental disorders in children with blindness or other severe visual impairment. As ASD and SVI’ signs and symptoms affect functioning and quality of life and different domains of functioning of children with this comorbidity, it is very important to support individuals and their families as soon as possible in the cycle of life and to promote specific interventions aimed to promote developmental potential of everyone with both ASD and VI, based on the unique balance between strengths, needs and abilities of everyone. Children and individuals with SVI and ASD and SVI are a very heterogeneous group, both about the areas of social interaction, communication, and behaviour, as well as about visual abilities and about all the other aspects of their neuropsychological and functional profiles that are influenced by their visual impairments itself, their ASD itself and the combination of them. In this paper, we aim to discuss some general principles useful to design and to develop specific interventions and to promote inclusion of children with ASD and SVI.

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27. Reich K, Dalferth M. [From the Placement Paradigm to Sustainable Support of Companies in the Integration of People with High-Functioning Autism – Results of an Employer Survey]. Die Rehabilitation. 2023.

As part of the AUT-1A project, 123 employers were surveyed by questionnaires about their experiences with the employment of autistic employees. The aim was to identify the factors that promote and hinder employment. The study indicates that the vocational qualification in vocational training centers (BBW) has a positive effect on sustainable employment of people with autism spectrum diagnosis (ASD), but the support for companies is not sufficient yet. Also, a lack of education regarding autism-friendly environmental design as well as a lack of education about the diagnosis autism of the direct colleagues could be worked out.

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28. Reyes ZMD, Lynch E, Henry J, De Simone LM, Sobotka SA. Diagnosis of autism in a rare case of tyrosine hydroxylase deficiency: a case report. BMC medical genomics. 2023; 16(1): 78.

BACKGROUND: Tyrosine hydroxylase deficiency (THD) is a rare movement disorder with broad phenotypic expression caused by bi-allelic mutations in the TH gene, which encode for tyrosine hydroxylase (TH) protein. Some patients with THD have improvement in dystonia with carbidopa-levodopa, a synthetic form of dopamine typically used in Parkinson’s disease, and are considered to have dopa-responsive THD. THD has been found in 0.5-1 per million persons, although due to overlapping symptoms with other disorders and the need for genetic testing, prevalence is likely underestimated. Existing literature describes some patients with THD having intellectual disability, but comorbid autism spectrum disorder (ASD) has not been reported. CASE PRESENTATION: A nearly 3-year-old boy was referred to pediatric neurology due to hypotonia, delayed motor milestones, and expressive speech delay. Whole exome sequencing confirmed tyrosine hydroxylase deficiency, detecting a novel variant p.S307C first reported here. The child was treated with carbidopa-levodopa with an excellent response, resulting in improved balance, fewer falls, and improved ability to jump, run and climb stairs. He was determined to have dopa-responsive THD. Due to his delays in expressive speech, the boy also had an assessment with a developmental and behavioral pediatrician, who identified a pattern of social pragmatic speech delay, sensory sensitivities, and restricted interests, and determined that he met criteria for a diagnosis of ASD. CONCLUSIONS: While ASD can stand alone as a clinical diagnosis, it is also a cardinal feature of other genetically-based neurological disorders. To our knowledge, this is the first case that describes a patient with both disorders. Perhaps THD may be among the genetic disorders linked with ASD.

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29. Rosenau KA, Hotez E, Fernandes P, Gomez C, Eagan K, Shea L, Kuo A. Anxiety and Depression in Autistic College Students: The Freshman Survey Results. Cureus. 2023; 15(3): e35820.

Objective Mental health among undergraduate students is a growing concern in higher education, but relatively little is known about the mental health of autistic college students. In order to better understand the unique needs of this population, the present study examines whether demographic and psychosocial correlates of anxiety and depression differ in autistic first-year college students and their non-autistic peers. Methods Secondary data analysis was conducted utilizing population-weighted data of full-time college students in their first year attending four-year colleges and universities in 2016, 2018, and 2019. Autistic and non-autistic students who self-identified as having frequent anxiety or depression were compared in terms of demographic characteristics, physical and emotional health, and academic aspirations and achievement. Results The majority of first-year students with frequent anxiety or depression in this sample tended to be white and had parents who completed a bachelor’s degree or went to graduate school, with higher rates of male students in the autistic group. While autistic college freshmen with frequent anxiety or depression self-report lower overall quality of physical health (below average or lowest 10% reported by 57.3% vs. 37.1%) and higher rates of learning disabilities (25.3% vs. 4.6%) and psychological disorders (62.3% vs. 29.3%), these students also tend to outperform their non-autistic peers on standardized academic testing. Conclusion As autistic students are investing in themselves through their education and future careers, practitioners and researchers alike should be investing in accessible physical and mental health services in order to help set autistic students up for success in college and beyond.

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30. Simeone PJ, Schlosser RW, Frampton SE, Shane HC, Wendt O. Miniature Linguistic Systems for Individuals With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Journal of speech, language, and hearing research : JSLHR. 2023: 1-24.

PURPOSE: Miniature linguistic systems (also known as matrix training) is a method of organizing learning targets to achieve generative learning or recombinative generalization. This systematic review is aimed at determining whether matrix training is effective for individuals with autism spectrum disorder (ASD) in terms of improving recombinative generalization for instruction-following, expressive language, play skills, and literacy skills. METHOD: A systematic review methodology was employed to limit bias in the various review stages. A multifaceted search was conducted. Potential primary studies were imported into Covidence, a systematic review software, and inclusion criteria were applied. Data were extracted regarding (a) participant characteristics, (b) matrix designs, (c) intervention methods, and (d) dependent variable. A quality appraisal using the What Works Clearinghouse (WWC) Single-Case Design Standards (Version 1.0, Pilot) was carried out. In addition to the visual analysis of the data, an effect size estimate, non-overlap of all pairs (NAP), was generated for each participant. Independent t tests and between-subjects analyses of variance were conducted to identify moderators of effectiveness. RESULTS: Twenty-six studies including 65 participants met criteria for inclusion. All included studies were single-case experimental designs. Eighteen studies received a rating of Meets Standards Without Reservations or Meets Standards With Reservations. The aggregated combined NAP scores for acquisition, recombinative generalization, and maintenance of a range of outcomes were in the high range. CONCLUSIONS: Findings suggested that matrix training is an effective teaching method for individuals with ASD for acquisition, recombinative generalization, and maintenance of a range of outcomes. Statistical analyses to identify moderators of effectiveness were insignificant. Based on the WWC Single-Case Design Standards matrix training meets criteria to be considered an evidence-based practice for individuals with ASD.

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31. Son JW. Advancing Research on Autistic Savants: A Call for Increased Focus and Attention. Soa–ch’ongsonyon chongsin uihak = Journal of child & adolescent psychiatry. 2023; 34(2): 62.

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32. Wahdan MM, Malak MZ, Al-Amer R, Ayed A, Russo S, Berte DZ. Effect of incredible years autism spectrum and language delays (IY-ASD) program on stress and behavioral management skills among parents of children with autism spectrum disorder in Palestine. Journal of pediatric nursing. 2023; 72: 45-52.

PURPOSE: This study purposed to evaluate the effect of the Incredible Years Autism Spectrum and Language Delays (IY-ASD) program in reducing parents’ stress and improving aggressive and disruptive behaviors in the parents among parents of children with autism spectrum disorder in Palestine. DESIGN AND METHODS: A one-group pre-posttest design was used. Thirty-four parents who enrolled in the Palestinian Child Institute in Nablus were recruited. RESULTS: Findings revealed a significant difference between parents’ total stress pre and post-IY-ASD (t = 1.2, p < 0.01 and parents' behavioral management skills toward their children with autism spectrum disorder. The study demonstrated that the IY-ASD program for 16 sessions reduced stress among parents of children with autism spectrum disorder in Palestine and improved aggressive and disruptive behaviors in the parents. CONCLUSION: The IY-ASD program can be successfully implemented for parents of this cohort group. PRACTICE IMPLICATIONS: Healthcare providers can adopt such a program for enhancing parenting roles with their children experiencing autism spectrum disorder.

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33. Xi A, Cai SQ, Yan HF, Tian Y, Cai J, Yang XM, Wang JM, Xing GG. CSMD3 deficiency leads to motor impairments and autism-like behaviors via dysfunction of cerebellar Purkinje cells in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2023.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with highly heritable heterogeneity. Mutations of CUB and sushi multiple domains 3 (CSMD3) gene have been reported in individuals with ASD. However, the underlying mechanisms of CSMD3 for the onset of ASD remain unexplored. Here, using male CSMD3-knock out (CSMD3(-/-) ) mice, we found that genetic deletion of CSMD3 produced core autistic-like symptoms (social interaction deficits, restricted interests, repetitive and stereotyped behaviors) and motor dysfunction in mice, indicating that CSMD3 gene can be considered as a candidate for ASD. Moreover, we discovered that ablation of CSMD3 in mice led to abnormal cerebellar Purkinje cells (PCs) morphology in Crus I/II lobules, including aberrant developmental dendritogenesis and spinogenesis of PCs. Furthermore, combining in vivo fiber photometry calcium imaging and ex vivo electrophysiological recordings, we showed that the CSMD3 (-/-) mice exhibited an increased neuronal activity (calcium fluorescence signals) in PCs of Crus I/II lobules in response to movement activity, as well as an enhanced intrinsic excitability of PCs and an increase of excitatory rather than inhibitory synaptic input to the PCs, and an impaired long-term depression (LTD) at the parallel fibers (PF)-PC synapse. These results suggest that CSMD3 plays an important role in cerebellar PCs development. Loss of CSMD3 causes abnormal PCs morphology and dysfunction in the cerebellum, which may underlie the pathogenesis of motor deficits and core autistic-like symptoms in CSMD3 (-/-) mice. Our findings provide novel insight into the pathophysiological mechanisms by which CSMD3 mutations cause impairments in cerebellar function that may contribute to ASD.Significance Statement:Autism spectrum disorder (ASD) is a neurodevelopmental disorder with highly heritable heterogeneity. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD. Recently, a novel giant gene CSMD3 encoding a protein with CUB and sushi multiple domains (CSMD) has been identified as a candidate gene for ASD. However, the underlying mechanisms of CSMD3 for the onset of ASD remain largely unknown. Here, we unravel that loss of CSMD3 results in abnormal morphology, increased intrinsic excitabilities and impaired synaptic plasticity in cerebellar PCs, subsequently leading to motor deficits and ASD-like behaviors in mice. These results provide novel insight into the pathophysiological mechanisms by which CSMD3 mutations cause impairments in cerebellar function that may contribute to ASD.

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34. Xue H, Zhang L, Wang J, Liu W, Liu S, Ming D. Dynamic eye avoidance patterns in the high autistic traits group: An eye-tracking study. Frontiers in psychiatry. 2023; 14: 1086282.

INTRODUCTION: Reduced fixation to the eye area is the main characteristic of social deficits associated with Autism Spectrum Disorder; a similar pattern may exist in individuals with high autistic traits. However, their scanning patterns to the eye area of emotional faces are still unclear on the time scale. METHODS: In the present study, we recruited 46 participants and divided them into the high autistic traits (HAT) group (23 participants) and the low autistic traits (LAT) group (20 participants) based on their Autism Spectrum Quotient (AQ) scores. Moreover, we captured their eye movement patterns when observing different angular emotional faces. We extracted the proportional fixation time to the eye area under different time windows. RESULTS: The results showed that the fixation time of the HAT group was always significantly smaller than that of the LAT group (p < 0.05), and the difference between the two groups increased in the middle and late stages of face presentation. The results of the linear regression analysis showed that the proportional fixation time was negatively correlated with AQ scores (p < 0.05), indicating that the proportional fixation time to the eye area could be a potential indicator to measure the level of autistic traits. We then calculated the latency to orient the eye area and the latency to disengage the eye area to explore the priority of observation of the eyes. The results showed that compared with the LAT group, the HAT group has a longer latency to orient the eye area (p < 0.05) and has longer latency to disengage the eye area (p < 0.05), illustrating that the HAT group saw the eyes more slowly and left them faster.

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35. Yamada M, Kato TA, Katsuki RI, Yokoi H, Igarashi M, Komine Y, Kamata Y, Kato N, Iwanami A, Ohta H. Pathological social withdrawal in autism spectrum disorder: A case control study of hikikomori in Japan. Frontiers in psychiatry. 2023; 14: 1114224.

INTRODUCTION: Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of ASD are associated with hikikomori. METHODS: Thirty-nine adult male patients with a diagnosis of ASD attending our outpatient clinic for neurodevelopmental disabilities were subjected to a structured interview regarding social withdrawal, various self-administered questionnaires, and blood tests. Through structured interviews, the subjects were divided into two groups: (Group 1) ASD with hikikomori condition and (Group 2) ASD without hikikomori condition. Sixteen subjects qualified as hikikomori and 23 subjects qualified as subjects without hikikomori. Age, sex, autism spectrum quotient (AQ), Autism Diagnostic Observation Schedule (ADOS), and FIQ were matched. RESULTS: Compared to non-hikikomori controls, hikikomori cases were likely to have stronger sensory symptoms, lower uric acid (UA) (p = 0.038), and higher rates of atopic dermatitis (p = 0.01). Cases showed more severe depressive and social anxiety symptoms based on self-rated scales: Patient Heath Questionnaire 9 (PHQ-9) (p < 0.001) and Liebowitz Social Anxiety Scale Japanese Version (LSAS-J) (p = 0.04). Tarumi's Modern-Type Depression Trait Scale (TACS-22), which measure traits of Modern-Type Depression (MTD), were significantly higher in cases (p = 0.003). CONCLUSION: The present study has suggested that ASD patients with hikikomori were more likely to have higher sensory abnormalities, comorbid atopic dermatitis, lower UA, stronger depressive, and anxiety tendency. Evaluating and approaching these aspects are important for appropriate interventions in ASD with hikikomori. Further investigations should be conducted to validate our pilot findings.

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36. Zhang J, Ji G, Gao X, Guan J. Single-nucleus gene and gene set expression-based similarity network fusion identifies autism molecular subtypes. BMC bioinformatics. 2023; 24(1): 142.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is highly phenotypically and genetically heterogeneous. With the accumulation of biological sequencing data, more and more studies shift to molecular subtype-first approach, from identifying molecular subtypes based on genetic and molecular data to linking molecular subtypes with clinical manifestation, which can reduce heterogeneity before phenotypic profiling. RESULTS: In this study, we perform similarity network fusion to integrate gene and gene set expression data of multiple human brain cell types for ASD molecular subtype identification. Then we apply subtype-specific differential gene and gene set expression analyses to study expression patterns specific to molecular subtypes in each cell type. To demonstrate the biological and practical significance, we analyze the molecular subtypes, investigate their correlation with ASD clinical phenotype, and construct ASD molecular subtype prediction models. CONCLUSIONS: The identified molecular subtype-specific gene and gene set expression may be used to differentiate ASD molecular subtypes, facilitating the diagnosis and treatment of ASD. Our method provides an analytical pipeline for the identification of molecular subtypes and even disease subtypes of complex disorders.

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37. Zhang Y, Li Y, Guo R, Xu W, Liu X, Zhao C, Guo Q, Xu W, Ni X, Hao C, Cui Y, Li W. Genetic diagnostic yields of 354 Chinese ASD children with rare mutations by a pipeline of genomic tests. Frontiers in genetics. 2023; 14: 1108440.

Purpose: To establish an effective genomic diagnosis pipeline for children with autism spectrum disorder (ASD) for its genetic etiology and intervention. Methods: A cohort of 354 autism spectrum disorder patients were obtained from Beijing Children’s Hospital, Capital Medical University. Peripheral blood samples of the patients were collected for whole genome sequencing (WGS) and RNA sequencing (RNAseq). Sequencing data analyses were performed for mining the single nucleotide variation (SNV), copy number variation (CNV) and structural variation (SV). Sanger sequencing and quantitative PCR were used to verify the positive results. Results: Among 354 patients, 9 cases with pathogenic/likely pathogenic copy number variation and 10 cases with pathogenic/likely pathogenic single nucleotide variations were detected, with a total positive rate of 5.3%. Among these 9 copy number variation cases, 5 were de novo and 4 were inherited. Among the 10 de novo single nucleotide variations, 7 were previously unreported. The pathological de novo mutations account for 4.2% in our cohort. Conclusion: Rare mutations of copy number variations and single nucleotide variations account for a relatively small proportion of autism spectrum disorder children, which can be easily detected by a genomic testing pipeline of combined whole genome sequencing and RNA sequencing. This is important for early etiological diagnosis and precise management of autism spectrum disorder with rare mutations.

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38. Zhou H, Feng XL. Autism Spectrum Disorders: Advances in Proteomics. Protein and peptide letters. 2023.

Autism is a class of developmental disorders with extremely high rates of disability affecting patients throughout their lives. There is no cure to date clinically, and early rehabilitation interventions can improve some of the behavioral problems of autistic patients, but these are limited by age and often have minimal effects in older adults with autism. Early diagnosis is also necessary while developing effective autism therapies. At present, the early diagnosis of autism is dependent on the search for effective markers in an attempt to screen differentially expressed proteins in autistic patients using high-throughput assays, such as synaptic scaffolding proteins, microtubule-associated proteins, apolipoproteins, immunoglobulin G complement factor-related proteins, etc. It would also be a big step forward for mechanistic studies of autism if a valid biomarker for autism could be found.

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