1. Byres L, Morris E, Austin J. Exploring Autistic adults’ perspectives on genetic testing for autism. Genetics in medicine : official journal of the American College of Medical Genetics. 2023: 100021.

PURPOSE: To investigate the perspectives of Autistic adults regarding genetic testing for autism. Though previous studies have explored the perceptions of genetic testing for autism among a variety of different stakeholders, to our knowledge none have explored the perceptions of Autistic adults. METHODS: We distributed a web-based survey via social media to English-speaking Autistic adults. The survey assessed individuals’ experiences with, attitudes towards, and interest in genetic testing for autism, and their perceptions of its potential benefits and harms. RESULTS: In total 461 respondents completed the survey: while 27% would have wanted genetic testing during childhood, 74% felt that it should only be offered if the Autistic individual is able to consent and 49% felt that genetic testing for autism should not be done at all. Smaller proportions felt testing should be routinely offered to Autistic adults and children (35% and 26% respectively). 40% felt that genetic testing was only harmful, and 15% felt it was only beneficial. CONCLUSION: Autistic adults have concerns about genetic testing for autism. Additional work is required to bridge the divide between the Autistic community and health care providers and families to identify if and when genetic testing should be offered.

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2. Chen WX, Chen YR, Peng MZ, Liu X, Cai YN, Huang ZF, Yang SY, Huang JY, Wang RH, Yi P, Liu L. Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases. Journal of autism and developmental disorders. 2023.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

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3. Davut G, Onur D, Hüseyin G. Autistic features and executive functions in first episode psychosis: Associations with functionality and quality of life. Early intervention in psychiatry. 2023.

AIM: The present study aimed at investigating the relationships between autistic features and cognitive deficits, functionality and quality of life in first episode psychosis (FEP) patients. METHODS: Sixty FEP patients [mean age (SD) = 32.53 (10.74), n = 23 female, n = 37 male] were enrolled in this cross-sectional study. Data was collected using a sociodemographic and clinical data form, the Positive and Negative Syndrome Scale (PANSS), the PANSS Autism Severity Score (PAUSS), the Personal and Social Performance Scale (PSP), the Frontal Assessment Battery (FAB), and the World Health Organization Quality of Life Scale Short Form in Turkish Version (WHOQOL-BREF TR). RESULTS: Autistic symptom severity was found to be higher in males than females, and higher in patients with a family history of psychotic disorder. An inverse relationship was found between the duration of education and the severity of autistic symptoms. While there was an inverse relationship between autistic symptom severity and executive functions and functionality, no significant correlation was found with quality of life. Negative symptom severity was a predictor of executive functions and functionality. No significant difference was observed between autistic and psychotic domains which were related to executive functions. CONCLUSIONS: Our study is the first to examine the relationship between autistic/psychotic symptoms and executive functions and functionality in patients with FEP. The results show that autistic symptoms are associated with worse social and personal functioning and worse executive functions in patients with FEP. Longitudinal follow-up studies with larger samples are required to determine the direction of the relations.

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4. Kung KTF. Autistic Traits, Gender Minority Stress, and Mental Health in Transgender and Non-Binary Adults. Journal of autism and developmental disorders. 2023.

The present study investigated the relation between autistic traits and gender minority stress and the relative importance of autistic traits and gender minority stress in predicting mental health outcomes in gender minority adults. An online survey was completed by 90 transgender women, 72 transgender men, 48 non-binary individuals assigned male at birth (AMAB), and 98 non-binary individuals assigned female at birth (AFAB). Autistic traits positively correlated with internalised transphobia in the non-binary groups. In general, higher autistic traits and gender minority stress correlated with poorer mental health outcomes. After controlling for gender minority stress, autistic traits accounted for additional variance of suicidality across gender minority groups, anxiety symptoms in the non-binary groups, and all mental health outcomes in non-binary AFAB.

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5. Nielsen TC, Nassar N, Boulton KA, Guastella AJ, Lain SJ. Estimating the Prevalence of Autism Spectrum Disorder in New South Wales, Australia: A Data Linkage Study of Three Routinely Collected Datasets. Journal of autism and developmental disorders. 2023.

Routinely collected data help estimate the prevalence of autism spectrum disorder (ASD) in jurisdictions without active autism surveillance. We created a population-based cohort of 1,211,834 children born in 2002-2015 in New South Wales, Australia using data linkage. Children with ASD were identified in three datasets – disability services, hospital admissions, and ambulatory mental health data. The prevalence of ASD in the cohort was 1.3% by age 12 and prevalence at age 6 increased an average of 4.1% per year (95% Confidence Interval, 3.3%, 4.8%). Most children with ASD were identified in disability services data (87%), although data linkage identified 1,711 additional cases that were more likely female, older at first contact, and living in major cities and less disadvantaged areas.

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6. Platero RL, López-Sáez M. Community responses to LGBT+ adults with intellectual and developmental disabilities during the COVID-19 confinement in Madrid. International social work. 2023; 66(1): 107-16.

A group of 50 people with intellectual and developmental disabilities (IDDs) as well as diverse sexualities and gender identities in Madrid participated in a feminist community-based project, which supported them through the first wave of the pandemic. Facilitated by professionals, the project offered online meetings twice a month, helping them to articulate their needs and promote their agency over their choices and experiences. Based on their demands, participants chose the topics they wanted to discuss, proposed activities, and were the center of the program, while facilitators set up and maintained the online space, helping with participation and access to information and resources. Through this transformative experience, the members of the group developed friendship networks and started their activism, making public appearances in video campaigns and mainstream newspapers to make their needs visible to peers, families, social workers, policy makers, and nongovernmental organizations (NGOs). This research is part of a larger project that tackles the psychosocial factors that affected Spanish people with sexual and gender diversity during the first wave of the pandemic.

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7. Qian J, Guan X, Xie B, Xu C, Niu J, Tang X, Li CH, Colecraft HM, Jaenisch R, Liu XS. Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons. Science translational medicine. 2023; 15(679): eadd4666.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of methyl CpG-binding protein 2 (MECP2) on the X chromosome in young females. Reactivation of the silent wild-type MECP2 allele from the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female patients with RTT. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 from Xi in RTT human embryonic stem cells (hESCs) and derived neurons. Demethylation of the MECP2 promoter by dCas9-Tet1 with target single-guide RNA reactivated MECP2 from Xi in RTT hESCs without detectable off-target effects at the transcriptional level. Neurons derived from methylation-edited RTT hESCs maintained MECP2 reactivation and reversed the smaller soma size and electrophysiological abnormalities, two hallmarks of RTT. In RTT neurons, insulation of the methylation-edited MECP2 locus by dCpf1-CTCF (a catalytically dead Cpf1 fused with CCCTC-binding factor) with target CRISPR RNA enhanced MECP2 reactivation and rescued RTT-related neuronal defects, providing a proof-of-concept study for epigenome editing to treat RTT and potentially other dominant X-linked diseases.

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8. Thabault M, Turpin V, Balado É, Fernandes-Gomes C, Huot AL, Cantereau A, Fernagut PO, Jaber M, Galvan L. Age-related behavioral and striatal dysfunctions in Shank3(ΔC/ΔC) mouse model of autism spectrum disorder. The European journal of neuroscience. 2023.

Autism spectrum disorders (ASD) are defined as a set of neurodevelopmental disorders and a lifelong condition. In mice, most of the studies focused on the developmental aspects of these diseases. In this paper, we examined the evolution of motor stereotypies through adulthood in the Shank3ΔC/ΔC mouse model of ASD, and their underlying striatal alterations, at 10 weeks, 20 weeks, and 40 weeks. We highlighted that motor stereotypies worsened at 40 weeks possibly carried by earlier striatal medium spiny neurons (MSN) alterations in GABAergic transmission and morphology. Moreover, we report that 20 weeks could be a critical time-point in the striatal-related ASD physiopathology, and we suggest that MSN alterations may not be the direct consequence of developmental issues, but rather be a consequence of other impairments occurring earlier.

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9. Turygin N, Matson JL, Adams H. Retraction notice to « Prevalence of co-occurring disorders in a sample of adults with mild and moderate intellectual disabilities who reside in a residential treatment setting » [Research in Developmental Disabilities 35/7 (2014) 1802-1808]. Research in developmental disabilities. 2023; 134: 104426.

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10. Wallis KE, Adebajo T, Bennett AE, Drye M, Gerdes M, Miller JS, Guthrie W. Short report: Prevalence of autism spectrum disorder in a large pediatric primary care network. Autism : the international journal of research and practice. 2023: 13623613221147396.

Historically, children from non-Hispanic Black and Hispanic backgrounds, those from lower-income families, and girls are less likely to be diagnosed with autism spectrum disorder. Under-identification among these historically and contemporaneously marginalized groups can limit their access to early, autism spectrum disorder-specific interventions, which can have long-term negative impacts. Recent data suggest that some of these trends may be narrowing, or even reversing. Using electronic health record data, we calculated autism spectrum disorder prevalence rates and age of first documented diagnosis across socio-demographic groups. Our cohort included children seen at young ages (when eligible for screening in early childhood) and again at least after 4 years of age in a large primary care network. We found that autism spectrum disorder prevalence was unexpectedly higher among Asian children, non-Hispanic Black children, children with higher Social Vulnerability Index scores (a measure of socio-economic risk at the neighborhood level), and children who received care in urban primary care sites. We did not find differences in the age at which autism spectrum disorder diagnoses were documented in children’s records across these groups. Receiving primary care at an urban site (regardless of location of specialty care) appeared to account for most other socio-demographic differences in autism spectrum disorder prevalence rates, except among Asian children, who remained more likely to be diagnosed with autism spectrum disorder after controlling for other factors. We must continue to better understand the process by which children with autism spectrum disorder from traditionally under-identified and under-served backgrounds come to be recognized, to continue to improve the equity of care.

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11. Yang Y, Booker SA, Clegg JM, Quintana-Urzainqui I, Sumera A, Kozic Z, Dando O, Martin Lorenzo S, Herault Y, Kind PC, Price DJ, Pratt T. Identifying foetal forebrain interneurons as a target for monogenic autism risk factors and the polygenic 16p11.2 microdeletion. BMC neuroscience. 2023; 24(1): 5.

BACKGROUND: Autism spectrum condition or ‘autism’ is associated with numerous genetic risk factors including the polygenic 16p11.2 microdeletion. The balance between excitatory and inhibitory neurons in the cerebral cortex is hypothesised to be critical for the aetiology of autism making improved understanding of how risk factors impact on the development of these cells an important area of research. In the current study we aim to combine bioinformatics analysis of human foetal cerebral cortex gene expression data with anatomical and electrophysiological analysis of a 16p11.2(+/-) rat model to investigate how genetic risk factors impact on inhibitory neuron development. METHODS: We performed bioinformatics analysis of single cell transcriptomes from gestational week (GW) 8-26 human foetal prefrontal cortex and anatomical and electrophysiological analysis of 16p11.2(+/-) rat cerebral cortex and hippocampus at post-natal day (P) 21. RESULTS: We identified a subset of human interneurons (INs) first appearing at GW23 with enriched expression of a large fraction of risk factor transcripts including those expressed from the 16p11.2 locus. This suggests the hypothesis that these foetal INs are vulnerable to mutations causing autism. We investigated this in a rat model of the 16p11.2 microdeletion. We found no change in the numbers or position of either excitatory or inhibitory neurons in the somatosensory cortex or CA1 of 16p11.2(+/-) rats but found that CA1 Sst INs were hyperexcitable with an enlarged axon initial segment, which was not the case for CA1 pyramidal cells. LIMITATIONS: The human foetal gene expression data was acquired from cerebral cortex between gestational week (GW) 8 to 26. We cannot draw inferences about potential vulnerabilities to genetic autism risk factors for cells not present in the developing cerebral cortex at these stages. The analysis 16p11.2(+/-) rat phenotypes reported in the current study was restricted to 3-week old (P21) animals around the time of weaning and to a single interneuron cell-type while in human 16p11.2 microdeletion carriers symptoms likely involve multiple cell types and manifest in the first few years of life and on into adulthood. CONCLUSIONS: We have identified developing interneurons in human foetal cerebral cortex as potentially vulnerable to monogenic autism risk factors and the 16p11.2 microdeletion and report interneuron phenotypes in post-natal 16p11.2(+/-) rats.

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