1. AlAli FA, Drdir T, Yahya A, Al Amiri E. Variants of the GNAI1 gene manifest as Prader-Willi-like syndrome: Case report with literature review. Clin Dysmorphol;2024 (Apr 1);33(2):69-74.

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2. Barnes GL, Ozsivadjian A, Baird G, Absoud M, Hollocks MJ. Investigating the Effects of Transdiagnostic Processes on Anxiety and Depression Symptoms in Autistic Young People: the Mediating Role of Emotion Dysregulation. J Autism Dev Disord;2024 (Mar 4)

Internalising symptoms are elevated in autism compared to the general population. Few studies have investigated emotional dysregulation (ED) as a potential mediator between specific transdiagnostic processes and anxiety and depression symptoms in autistic youth. In a sample of 94 autistic young people aged 5-18 years referred to a specialist clinic for an autism evaluation, we tested the effects of ED as a mediator between cognitive inflexibility (CI), intolerance of uncertainty (IU) and alexithymia with anxiety and depression symptoms, using structural equation modelling. Effect sizes were compared to a non-autistic comparison group (n = 84). CI and alexithymia did not significantly predict depression symptoms in autistic young people, directly nor via ED. Relationships between CI/alexithymia and depression were fully mediated by ED in the non-autistic sample. There was a direct effect of CI on anxiety in the non-autistic group but not in those with a diagnosis. IU predicted depression symptoms in the autism group; and ED mediated this relationship only in those who did not receive a diagnosis. IU directly predicted anxiety in both groups and this relationship did not occur via ED. The finding of a direct pathway from IU to anxiety and depression in autistic youth is consistent with the literature. The finding that CI did not predict anxiety or depression in those with autism is novel, as was the finding that ED mediated relationships between alexithymia and anxiety/depression symptoms in both samples. The findings may have important implications for the delivery of psychological interventions for autistic youth.

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3. Burke H, Jiang S, Stern TA. Management of Individuals With Autism Spectrum Disorder in Clinical Settings. Prim Care Companion CNS Disord;2024 (Mar 5);26(2)

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry. Prim Care Companion CNS Disord 2024;26(2):23f03584. Author affiliations appear at the end of this article.

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4. Carnevali L, Valori I, Mason G, Altoè G, Farroni T. Interpersonal motor synchrony in autism: a systematic review and meta-analysis. Front Psychiatry;2024;15:1355068.

INTRODUCTION: Interpersonal motor synchrony (IMS) is the spontaneous, voluntary, or instructed coordination of movements between interacting partners. Throughout the life cycle, it shapes social exchanges and interplays with intra- and inter-individual characteristics that may diverge in Autism Spectrum Disorder (ASD). Here we perform a systematic review and meta-analysis to summarize the extant literature and quantify the evidence about reduced IMS in dyads including at least one participant with a diagnosis of ASD. METHODS: Empirical evidence from sixteen experimental studies was systematically reviewed, encompassing spontaneous and instructed paradigms as well as a paucity of measures used to assess IMS. Of these, thirteen studies (n = 512 dyads) contributed measures of IMS with an in situ neurotypical partner (TD) for ASD and control groups, which could be used for meta-analyses. RESULTS: Reduced synchronization in ASD-TD dyads emerged from both the systematic review and meta-analyses, although both small and large effect sizes (i.e., Hedge’s g) in favor of the control group are consistent with the data (Hedge’s g = .85, p < 0.001, 95% CI[.35, 1.35], 95% PI[-.89, 2.60]). DISCUSSION: Uncertainty is discussed relative to the type of task, measures, and age range considered in each study. We further discuss that sharing similar experiences of the world might help to synchronize with one another. Future studies should not only assess whether reduced IMS is consistently observed in ASD-TD dyads and how this shapes social exchanges, but also explore whether and how ASD-ASD dyads synchronize during interpersonal exchanges.

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5. Forcelini CM, Ampese R, Melo HY, Pasin CPN, Pádua JRD, Spanholo CB, Hoffmann FE, Diniz JB, Capponi LCZ, Souza L, Zortea M. Proposal of a screening instrument for autism spectrum disorder in children (Mini-TEA Scale). Arq Neuropsiquiatr;2024 (Mar);82(3):1-8.

BACKGROUND:  Autism spectrum disorder (ASD) requires trained professionals for its adequate diagnosis. There is a shortage of such professionals in Brazil. Screening tools could identify priority cases. The only instrument for that in Brazilian Portuguese is employed for toddlers up to 2.5 years old. OBJECTIVE:  The Mini-TEA scale was conceived and tested as a screening for children from 2.5 to 12 years old. METHODS:  After local ethics committee’s approval, this study was conducted from December 2022 to April 2023 in the Associação de Pais e Amigos dos Excepcionais, Passo Fundo/RS, of invitations to children’s parents/relatives who were under evaluation for ASD and by local advertisement. Inclusion criteria were age from 2.5 to 12 years old; consent from the child’s legal guardians. 75 children’s parents/relatives were interviewed using the 15-item Mini-TEA scale. After that, children were evaluated for the diagnosis of ASD by a pediatric neurologist. Sensibility and specificity for ASD diagnosis along the Mini-TEA scores were measured. Experts and target population evaluated the validity/reliability of the Mini-TEA scale. The reproducibility of the scores was assessed about 40 days later. RESULTS:  From the 75 participants, 28 received a diagnosis of ASD. Scores ≥ 10 on the Mini-TEA scale require further evaluation of the children (sensitivity 100%; specificity 68%). Content validity coefficient (CVC) rendered values > 0.80 (acceptable). Test-retest analyzes with the intraclass correlation coefficient (ICC) indicated excellent reliability (> 0.90). The time spent for applying the screening was about 10 minutes. CONCLUSION:  The Mini-TEA scale presents as an easy tool for screening ASD among children.

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6. Gülcü Üstün NS. A pathogenic P4HTM gene variant in two brothers with autism spectrum disorder. Psychiatr Genet;2024 (Apr 1);34(2):68-69.

Autism spectrum disorder is a neurodevelopmental condition that involves limitations in social communication and various stereotypical repetitive behaviors. Genetic and environmental factors both play a role in the etiology. Numerous genetic syndromes accompanying autism spectrum disorders have been reported. Hypoventilation, hypotonia, intellectual disability, epilepsy, eye abnormality (HIDEA) syndrome is a rare genetic condition consisting of a combination of features such as hypoventilation, hypotonia, intellectual disability, eye abnormalities, and epilepsy. Very few cases of HIDEA syndrome have been reported in the literature to date. To the best of our knowledge, no cases of comorbid autism spectrum disorder and HIDEA syndrome have previously been reported. This report describes two brothers with a pathogenic P4HTM gene variant and autism spectrum disorder. One was diagnosed with HIDEA syndrome, while the other was a healthy carrier.

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7. Harada Y, Ohyama J, Sano M, Ishii N, Maida K, Wada M, Wada M. Temporal characteristics of facial ensemble in individuals with autism spectrum disorder: examination from arousal and attentional allocation. Front Psychiatry;2024;15:1328708.

INTRODUCTION: Individuals with Autism Spectrum Disorder (ASD) show atypical recognition of facial emotions, which has been suggested to stem from arousal and attention allocation. Recent studies have focused on the ability to perceive an average expression from multiple spatially different expressions. This study investigated the effect of autistic traits on temporal ensemble, that is, the perception of the average expression from multiple changing expressions. METHODS: We conducted a simplified temporal-ensemble task and analyzed behavioral responses, pupil size, and viewing times for eyes of a face. Participants with and without diagnosis of ASD viewed serial presentations of facial expressions that randomly switched between emotional and neutral. The temporal ratio of the emotional expressions was manipulated. The participants estimated the intensity of the facial emotions for the overall presentation. RESULTS: We obtained three major results: (a) many participants with ASD were less susceptible to the ratio of anger expression for temporal ensembles, (b) they produced significantly greater pupil size for angry expressions (within-participants comparison) and smaller pupil size for sad expressions (between-groups comparison), and (c) pupil size and viewing time to eyes were not correlated with the temporal ensemble. DISCUSSION: These results suggest atypical temporal integration of anger expression and arousal characteristics in individuals with ASD; however, the atypical integration is not fully explained by arousal or attentional allocation.

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8. Houben F, den Heijer CD, Dukers-Muijrers NH, Smeets-Peels C, Hoebe CJ. Perceived barriers and facilitators to infection prevention and control in Dutch residential care facilities for people with intellectual and developmental disabilities: a cross-sectional study. BMC Public Health;2024 (Mar 5);24(1):704.

BACKGROUND: Adequate implementation of infection prevention and control (IPC) in residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDDs) is crucial to safeguarding this vulnerable population. Studies in this field are scarce. This study aimed to identify perceived barriers to and facilitators of IPC among professionals working in these settings, along with recommendations to improve IPC, to inform the development of targeted interventions. METHODS: We administered an online questionnaire to 319 professionals from 16 Dutch RCFs for people with IDDs (March 2021-March 2022). Perceived multilevel barriers and facilitators (guideline, client, interpersonal, organisational, care sector, and policy level) were measured on a 5-point Likert scale (totally disagree-totally agree). Recommendations were assessed using a 5-point Likert scale (not at all helpful-extremely helpful), supplemented by an open-ended question. Barriers, facilitators, and recommendations were analysed by descriptive statistics. Open answers to recommendations were analysed through thematic coding. RESULTS: Barriers to IPC implementation included the client group (e.g., lack of hygiene awareness) (63%), competing values between IPC and the home-like environment (42%), high work pressure (39%), and the overwhelming quantity of IPC guidelines/protocols (33%). Facilitators included perceived social support on IPC between professionals and from supervisors (90% and 80%, respectively), procedural clarity of IPC guidelines/protocols (83%), and the sense of urgency for IPC in the organisation (74%). Main recommendations included the implementation of clear IPC policies and regulations (86%), the development of a practical IPC guideline (84%), and the introduction of structural IPC education and training programmes (for new staff members) (85%). Professionals also emphasised the need for IPC improvement efforts to be tailored to the local care context, and to involve clients and their relatives. CONCLUSIONS: To improve IPC in disability care settings, multifaceted strategies should be adopted. Initial efforts should involve clients (and relatives), develop a practical and context-specific IPC guideline, encourage social support among colleagues through interprofessional coaching, reduce workload, and foster an IPC culture including shared responsibility within the organisation.

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9. Hu Y, Sun X, Yao C, Luo S, Liu B, Xue M, Lyu H. Object-centered family interactions for young autistic children: a diary study. Sci Rep;2024 (Mar 5);14(1):5460.

Autistic Children often struggle with social interaction and communication, studies have found that many of them prefer to interact with objects than people. However, there is a lack of research exploring the specific characteristics and factors involved in interactions within families with autistic children where objects are the center of the interaction. This paper describes the process and findings of a diary study exploring how young autistic children interact with their families through objects in natural scenarios. A one-week diary study was conducted with six families with young autistic children. Diary videos were recorded onsite and coded later according to a social interaction behavior scheme with corresponding diary entries. Qualitative data analysis was conducted to reveal possible patterns. Results revealed ongoing difficulties in establishing and maintaining family interaction and identified influential factors of object-centered family interaction. The most prevalent pattern observed was parents taking the lead in interactions, followed by the child’s confirmation response. Remarkably, daily necessities emerged as potential physical mediums for enhancing family interactions, opening avenues for exploring tangible designs in human-computer interaction. These findings offer valuable implications for future research and the development of innovative designs that promote enriching interactions for autistic children and their families.

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10. Juan CX, Mao Y, Han X, Qian HY, Chu KK. EGR1 Regulates SHANK3 Transcription at Different Stages of Brain Development. Neuroscience;2024 (Mar 5);540:27-37.

The expression levels of SHANK3 are associated with autism spectrum disorder (ASD). The dynamic changes in SHANK3 expression during different stages of brain development may impact the progression of ASD. However, no studies or detailed analyses exploring the upstream mechanisms that regulate SHANK3 expression have been reported. In this study, we employed immunofluorescence to examine the expression of SHANK3 in brain organoids at various stages. Our results revealed elevated levels of SHANK3 expression in brain-like organoids at Day 60. Additionally, we utilized bioinformatics software to predict and analyze the SHANK3 gene’s transcription start site. Through the dual luciferase reporter gene technique, we identified core transcription elements within the SHANK3 promoter. Site-directed mutations were used to identify specific transcription sites of SHANK3. To determine the physical binding of potential transcription factors to the SHANK3 promoter, we employed electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Our findings demonstrated that the transcription factor EGR1 regulates SHANK3 expression by binding to the transcription site of the SHANK3 promoter. Although this study did not investigate the pathological phenotypes of human brain organoids or animal model brains with EGR1 deficiency, which could potentially substantiate the findings observed for SHANK3 mutants, our findings provide valuable insights into the relationship between the transcription factor, EGR1, and SHANK3. This study contributes to the molecular understanding of ASD and offers potential foundations for precise targeted therapy.

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11. Li X, Fu Q, Zhong M, Long Y, Zhao F, Huang Y, Zhang Z, Wen M, Chen K, Chen R, Ma X. Quantitative proteomics of the miR-301a/SOCS3/STAT3 axis reveals underlying autism and anxiety-like behavior. Mol Ther Nucleic Acids;2024 (Mar 12);35(1):102136.

Autism is a widespread neurodevelopmental disorder. Although the research on autism spectrum disorders has been increasing in the past decade, there is still no specific answer to its mechanism of action and treatment. As a pro-inflammatory microRNA, miR-301a is abnormally expressed in various psychiatric diseases including autism. Here, we show that miR-301a deletion and inhibition exhibited two distinct abnormal behavioral phenotypes in mice. We observed that miR-301a deletion in mice impaired learning/memory, and enhanced anxiety. On the contrary, miR-301a inhibition effectively reduced the maternal immune activation (MIA)-induced autism-like behaviors in mice. We further demonstrated that miR-301a bound to the 3’UTR region of the SOCS3, and that inhibition of miR-301a led to the upregulation of SOCS3 in hippocampus. The last result in the reduction of the inflammatory response by inhibiting phosphorylation of AKT and STAT3, and the expression level of IL-17A in poly(I:C)-induced autism-like features in mice. The obtained data revealed the miR-301a as a critical participant in partial behavior phenotypes, which may exhibit a divergent role between gene knockout and knockdown. Our findings ascertain that miR-301a negatively regulates SOCS3 in MIA-induced autism in mice and could present a new therapeutic target for ameliorating the behavioral abnormalities of autism.

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12. Li X, Qi S, Li W, Liu X, Xue Z, Yu T, Xun G. Cohen syndrome combined with psychiatric symptoms: a case report. BMC Psychiatry;2024 (Mar 4);24(1):180.

BACKGROUND: Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms. CASE REPORT: We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms. CONCLUSIONS: This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.

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13. Mohamad T, Lepage JF. Computing a cure for fragile-X syndrome. Brain Commun;2024;6(2):fcae066.

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14. Perkovich E, Laakman A, Mire S, Yoshida H. Conducting head-mounted eye-tracking research with young children with autism and children with increased likelihood of later autism diagnosis. J Neurodev Disord;2024 (Mar 4);16(1):7.

BACKGROUND: Over the past years, researchers have been using head-mounted eye-tracking systems to study young children’s gaze behaviors in everyday activities through which children learn about the world. This method has great potential to further our understanding of how millisecond-level gaze behaviors create multisensory experiences and fluctuate around social environments. While this line of work can yield insight into early perceptual experiences and potential learning mechanisms, the majority of the work is exclusively conducted with typically-developing children. Sensory sensitivities, social-communication difficulties, and challenging behaviors (e.g., disruption, elopement) are common among children with developmental disorders, and they may represent potential methodological challenges for collecting high-quality data. RESULTS: In this paper, we describe our research practices of using head-mounted eye trackers with 41 autistic children and 17 children with increased likelihood of later autism diagnosis without auditory or visual impairments, including those who are minimally or nonspeaking and/or have intellectual disabilities. The success rate in gathering data among children with autism was 92.68%. 3 of 41 children failed to complete the play-session, resulting in an 86.36% success rate among 1-4-year-olds and a 100.00% success rate among 5-8-year-olds. 1 of 17 children with increased likelihood of later autism diagnosis failed to complete the play-session, resulting in a success rate of 94.11%. There were numerous « challenging » behaviors relevant to the method. The most common challenging behaviors included taking the eye-tracking device off, elopement, and becoming distressed. Overall, among children with autism, 88.8% of 1-4-year-olds and 29.4% of 5-8-year-olds exhibited at least one challenging behavior. CONCLUSIONS: Research capitalizing on this methodology has the potential to reveal early, socially-mediated gaze behaviors that are relevant for autism screening, diagnosis, and intervention purposes. We hope that our efforts in documenting our study methodology will help researchers and clinicians effectively study early naturally-occuring gaze behaviors of children during non-experimental contexts across the spectrum and other developmental disabilities using head-mounted eye-tracking. Ultimately, such applications may increase the generalizability of results, better reflect the diversity of individual characteristics, and offer new ways in which this method can contribute to the field.

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15. Randall KN, McKown GL. Perceived Impact of the COVID-19 Pandemic on Adults with Intellectual and Developmental Disability: A Qualitative Study. J Intellect Disabil;2024 (Mar);28(1):118-136.

The current study examined the impact that the COVID-19 pandemic and resulting restrictions have had on individuals with intellectual and developmental disability. Semi-structured focus groups were conducted to collect data from participants who attended day programming by local community agency. Results indicate that the COVID-19 pandemic and its safety restrictions impacted participants’ knowledge of the disease, programming and work, relationships, activities, and emotions in ways that were both similar to and different from other findings in other populations. Implications of these findings for research and practice are discussed.

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16. Raspa M, Gwaltney A, Bann C, von Hehn J, Benke TA, Marsh ED, Peters SU, Ananth A, Percy AK, Neul JL. Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS). J Autism Dev Disord;2024 (Mar 5)

Rett syndrome is a severe neurodevelopmental disorder that affects about 1 in 10,000 females. Clinical trials of disease modifying therapies are on the rise, but there are few psychometrically sound caregiver-reported outcome measures available to assess treatment benefit. We report on a new caregiver-reported outcome measure, the Rett Caregiver Assessment of Symptom Severity (RCASS). Using data from the Rett Natural History Study (n = 649), we examined the factor structure, using both exploratory and confirmatory factor analysis, and the reliability and validity of the RCASS. The four-factor model had the best overall fit, which covered movement, communication, behavior, and Rett-specific symptoms. The RCASS had moderate internal consistency. Strong face validity was found with age and mutation type, and convergent validity was established with other similar measures, including the Revised Motor-Behavior Assessment Scale, Clinical Severity Scale, Clinical Global Impression Scale, and the Child Health Questionnaire. These data provide initial evidence that the RCASS is a viable caregiver-outcome measure for use in clinical trials in Rett syndrome. Future work to assess sensitivity to change and other measures of reliability, such as test-retest and inter-rater agreement, are needed.

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17. Shiraishi T, Katayama Y, Nishiyama M, Shoji H, Miyakawa T, Mizoo T, Matsumoto A, Hijikata A, Shirai T, Mayanagi K, Nakayama KI. The complex etiology of autism spectrum disorder due to missense mutations of CHD8. Mol Psychiatry;2024 (Mar 5)

CHD8 is an ATP-dependent chromatin-remodeling factor encoded by the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Although many studies have examined the consequences of CHD8 haploinsufficiency in cells and mice, few have focused on missense mutations, the most common type of CHD8 alteration in ASD patients. We here characterized CHD8 missense mutations in ASD patients according to six prediction scores and experimentally examined the effects of such mutations on the biochemical activities of CHD8, neural differentiation of embryonic stem cells, and mouse behavior. Only mutations with high prediction scores gave rise to ASD-like phenotypes in mice, suggesting that not all CHD8 missense mutations detected in ASD patients are directly responsible for the development of ASD. Furthermore, we found that mutations with high scores cause ASD by mechanisms either dependent on or independent of loss of chromatin-remodeling function. Our results thus provide insight into the molecular underpinnings of ASD pathogenesis caused by missense mutations of CHD8.

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18. Skaletski EC, Barry K, Dennis E, Donnelly R, Huerta C, Jones A, Schmidt K, Kabakov S, Ausderau KK, Li JJ, Travers BG. Sensorimotor Features and Daily Living Skills in Autistic Children With and Without ADHD. J Autism Dev Disord;2024 (Mar 5)

Attention-deficit/hyperactivity disorder (ADHD) commonly co-occurs in autistic children. However, additional research is needed to explore the differences in motor skills and sensory features in autistic children with and without ADHD, as well as the impacts of these factors on daily living skills (DLS). This observational study sought to fill this gap with 67 autistic children (6.14-10.84 years-old), 43 of whom had ADHD. Autistic children with ADHD demonstrated higher sensory features and lower motor skills than autistic children without ADHD. In examining autism and ADHD features dimensionally, we found that overall sensory features, seeking, and hyporesponsiveness were driven by both autism and ADHD features, whereas motor skills, enhanced perception, and hyperresponsiveness were driven by only autism features. Additionally, in using these dimensional variables of autism and ADHD features, we found that differences in motor skills, sensory and autism features, but not ADHD features, impact DLS of autistic children, with autism features and motor skills being the strongest individual predictors of DLS. Together, these results demonstrate the uniqueness of motor skills and sensory features in autistic children with and without ADHD, as well as how autism features, sensory features, and motor skills contribute to DLS, emphasizing the importance of a comprehensive understanding of each individual and complexities of human development when supporting autistic children.

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19. Soumier A, Lio G, Demily C. Current and future applications of light-sheet imaging for identifying molecular and developmental processes in autism spectrum disorders. Mol Psychiatry;2024 (Mar 5)

Autism spectrum disorder (ASD) is identified by a set of neurodevelopmental divergences that typically affect the social communication domain. ASD is also characterized by heterogeneous cognitive impairments and is associated with cooccurring physical and medical conditions. As behaviors emerge as the brain matures, it is particularly essential to identify any gaps in neurodevelopmental trajectories during early perinatal life. Here, we introduce the potential of light-sheet imaging for studying developmental biology and cross-scale interactions among genetic, cellular, molecular and macroscale levels of circuitry and connectivity. We first report the core principles of light-sheet imaging and the recent progress in studying brain development in preclinical animal models and human organoids. We also present studies using light-sheet imaging to understand the development and function of other organs, such as the skin and gastrointestinal tract. We also provide information on the potential of light-sheet imaging in preclinical drug development. Finally, we speculate on the translational benefits of light-sheet imaging for studying individual brain-body interactions in advancing ASD research and creating personalized interventions.

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20. Zhang S, Yang J, Ji D, Meng X, Zhu C, Zheng G, Glessner J, Qu HQ, Cui Y, Liu Y, Wang W, Li X, Zhang H, Xiu Z, Sun Y, Sun L, Li J, Hakonarson H, Li J, Xia Q. NASP gene contributes to autism by epigenetic dysregulation of neural and immune pathways. J Med Genet;2024 (Mar 5)

BACKGROUND: Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology. METHODS: Trio-based whole exome sequencing was conducted on ASD families. Genome editing technique was used to knock out the candidate causal gene in a relevant cell line. ATAC-seq, ChIP-seq and RNA-seq were performed to investigate the functional impact of knockout (KO) or mutation in the candidate gene. RESULTS: We identified a novel candidate gene NASP (nuclear autoantigenic sperm protein) for epigenetic dysregulation in ASD in a Chinese nuclear family including one proband with autism and comorbid atopic disease. The de novo likely gene disruptive variant tNASP(Q289X) subjects the expression of tNASP to nonsense-mediated decay. tNASP KO increases chromatin accessibility, promotes the active promoter state of genes enriched in synaptic signalling and leads to upregulated expression of genes in the neural signalling and immune signalling pathways. Compared with wild-type tNASP, tNASP(Q289X) enhances chromatin accessibility of the genes with enriched expression in the brain. RNA-seq revealed that genes involved in neural and immune signalling are affected by the tNASP mutation, consistent with the phenotypic impact and molecular effects of nasp-1 mutations in Caenorhabditis elegans. Two additional patients with ASD were found carrying deletion or deleterious mutation in the NASP gene. CONCLUSION: We identified novel epigenetic mechanisms mediated by tNASP which may contribute to the pathogenesis of ASD and its immune comorbidity.

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21. Zhao S, Cao R, Lin C, Wang S, Yu H. Differences in the link between social trait judgment and socio-emotional experience in neurotypical and autistic individuals. Sci Rep;2024 (Mar 5);14(1):5400.

Neurotypical (NT) individuals and individuals with autism spectrum disorder (ASD) make different judgments of social traits from others’ faces; they also exhibit different social emotional responses in social interactions. A common hypothesis is that the differences in face perception in ASD compared with NT is related to distinct social behaviors. To test this hypothesis, we combined a face trait judgment task with a novel interpersonal transgression task that induces measures social emotions and behaviors. ASD and neurotypical participants viewed a large set of naturalistic facial stimuli while judging them on a comprehensive set of social traits (e.g., warm, charismatic, critical). They also completed an interpersonal transgression task where their responsibility in causing an unpleasant outcome to a social partner was manipulated. The purpose of the latter task was to measure participants’ emotional (e.g., guilt) and behavioral (e.g., compensation) responses to interpersonal transgression. We found that, compared with neurotypical participants, ASD participants’ self-reported guilt and compensation tendency was less sensitive to our responsibility manipulation. Importantly, ASD participants and neurotypical participants showed distinct associations between self-reported guilt and judgments of criticalness from others’ faces. These findings reveal a novel link between perception of social traits and social emotional responses in ASD.

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22. Zhu Y, Yang Q, Gu J, Chen Z, Jing N, Jin T, Lin J, Wang X, Hu J, Ji G, An Y. ‘Environmental standard limit concentration’ arsenic exposure is associated with anxiety, depression, and autism-like changes in early-life stage zebrafish. J Hazard Mater;2024 (Mar 5);469:133953.

Arsenic is a worldwide environmental pollutant that can impair human health. Previous studies have identified mental disorders induced by arsenic, but the environmental exposure concentrations in the early life stages associated with these disorders are poorly understood. In the present study, early-life stage zebrafish were used to explore the effects on mental disorders under ‘environmental standard limit concentrations’ arsenic exposures of 5, 10, 50, 150, and 500 μg/L. The results showed that arsenic exposure at these concentrations changed the locomotor behavior in larval zebrafish and was further associated with anxiety, depression, and autism-like behavior in both larval and juvenile zebrafish. Changes were noted at benchmark dose limit (BMDL) concentrations as low as 0.81 μg/L. Transcriptomics showed that immediate early genes (IEGs) fosab, egr1, egr2a, ier2b, egr3, and jund were decreased after arsenic exposure in larval and juvenile zebrafish. Nervous system impairment and anxiety, depression, and autism-like behaviors in early-life stage zebrafish at ‘environmental standard limit concentrations’ may be attributed to the downregulation of IEGs. These findings in zebrafish provided new experimental support for an arsenic toxicity threshold for mental disorders, and they suggest that low levels of environmental chemicals may be causative developmental factors for mental disorders.

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