1. How Can Diagnostic Certainty of Autism Spectrum Disorder Be Achieved in Young Children?. Pediatr Dent;2023 (Jan 15);45(1):9.

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2. Erratum to: From autism to Zoom®: Spina bifida advocacy, care, education, and research in a changing world. J Pediatr Rehabil Med;2023 (Mar 3)

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3. Aljuwaiser M, Alayadhi N, Ozidu V, Shafik Zakhari SA, Rushdy R, Naguy A. Clinical Indications of Memantine in Psychiatry-Science or Art?. Psychopharmacol Bull;2023 (Feb 28);53(1):30-38.

BACKGROUND: Memenatine is USFDA approved for dementia of Alzheimer’s disease. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders. STUDY QUESTION: Memantine remains one of only few psychotropic drugs with antiglutamate activity. This might impart it a therapeutic potential in treatment-resistant major psychiatric disorders characterized by neuroprogression. We reviewed memantine basic pharmacology and its diversifying clinical indications while examining the extant evidence. METHODS: EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of November, 2022. RESULTS: Sound evidence supports use of memantine for major neuro-cognitive disorder due to Alzheimer’s disease and severe vascular dementia, obsessive-compulsive disorder, treatment-resistant schizophrenia, and, ADHD. Modicum evidence supports use of memantine for PTSD, GAD and pathological gambling. Less compelling evidence is present for use in catatonia. No evidence supports use for core symptoms of autism spectrum disorder. CONCLUSIONS: Memantine is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of memantine in these off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.

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4. Beopoulos A, Géa M, Fasano A, Iris F. RNA epitranscriptomics dysregulation: A major determinant for significantly increased risk of ASD pathogenesis. Front Neurosci;2023;17:1101422.

Autism spectrum disorders (ASDs) are perhaps the most severe, intractable and challenging child psychiatric disorders. They are complex, pervasive and highly heterogeneous and depend on multifactorial neurodevelopmental conditions. Although the pathogenesis of autism remains unclear, it revolves around altered neurodevelopmental patterns and their implications for brain function, although these cannot be specifically linked to symptoms. While these affect neuronal migration and connectivity, little is known about the processes that lead to the disruption of specific laminar excitatory and inhibitory cortical circuits, a key feature of ASD. It is evident that ASD has multiple underlying causes and this multigenic condition has been considered to also dependent on epigenetic effects, although the exact nature of the factors that could be involved remains unclear. However, besides the possibility for differential epigenetic markings directly affecting the relative expression levels of individual genes or groups of genes, there are at least three mRNA epitranscriptomic mechanisms, which function cooperatively and could, in association with both genotypes and environmental conditions, alter spatiotemporal proteins expression patterns during brain development, at both quantitative and qualitative levels, in a tissue-specific, and context-dependent manner. As we have already postulated, sudden changes in environmental conditions, such as those conferred by maternal inflammation/immune activation, influence RNA epitranscriptomic mechanisms, with the combination of these processes altering fetal brain development. Herein, we explore the postulate whereby, in ASD pathogenesis, RNA epitranscriptomics might take precedence over epigenetic modifications. RNA epitranscriptomics affects real-time differential expression of receptor and channel proteins isoforms, playing a prominent role in central nervous system (CNS) development and functions, but also RNAi which, in turn, impact the spatiotemporal expression of receptors, channels and regulatory proteins irrespective of isoforms. Slight dysregulations in few early components of brain development, could, depending upon their extent, snowball into a huge variety of pathological cerebral alterations a few years after birth. This may very well explain the enormous genetic, neuropathological and symptomatic heterogeneities that are systematically associated with ASD and psychiatric disorders at large.

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5. Bernard S, Doherty M, Porte H, Al-Bustani L, Murphy LE, Russell MC, Shaw SCK. Upholding autistic people’s human rights: A neurodiversity toolbox for autism research. Autism Res;2023 (Mar 7)

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6. Blackmore CE, Nolan A, Stoencheva V, Greenwood N, Liu-Thwaites N, Maltezos S, McAlonan GM. Comparison of an online adaptation of the Autism Diagnostic Observation Schedule-2 with its in-person version in an adult autism diagnostic service. BJPsych Open;2023 (Mar 6);9(2):e51.

BACKGROUND: Restrictions on in-person assessments during the COVID-19 pandemic were a challenge for an adult autism diagnostic service receiving over 600 referrals annually. The service sought to adapt the Autism Diagnostic Observation Schedule (ADOS-2) for online administration. AIMS: To investigate whether an online adaptation of the ADOS-2 performed comparably to the in-person ADOS-2. To obtain qualitative feedback from patients and clinicians regarding experiences of the online alternative. METHOD: Online ADOS-2 assessments were completed for 163 referred individuals. A matched-comparison group comprised 198 individuals seen for an in-person ADOS-2 assessment prior to COVID-19 restrictions. A two-way analysis of variance (ANOVA) was run to explore any effect of assessment type (online or in-person ADOS-2) and gender on total ADOS score. Qualitative feedback was collected from 46 patients and 8 clinicians involved in diagnostic decision-making after the online ADOS-2 assessment. RESULTS: A two-way ANOVA found no significant effect of assessment type or gender and no assessment type × gender interaction effect on total ADOS score. Qualitative feedback suggested that only 27% of patients would have preferred an in-person assessment. Nearly all clinicians reported gains from offering an online alternative. CONCLUSIONS: This is the first study to examine an online adaptation of ADOS-2 within an adult autism diagnostic service. It performed comparably to the in-person ADOS-2, making it a viable alternative when in-person assessments are not possible. As this clinic group has high rates of comorbid mental health difficulties, we encourage further work to determine whether online assessment approaches generalise to other services to increase options for patients and efficiencies for service delivery.

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7. Chang X, Sun L, Li R. Application of symbolic play test in identification of autism spectrum disorder without global developmental delay and developmental language disorder. BMC Psychiatry;2023 (Mar 6);23(1):138.

BACKGROUND: Children with autism spectrum disorders (ASD) usually experience difficulty regarding symbolic play. However, studies on whether symbolic play test (SPT) can differentiate between ASD and other developmental disorders are inconsistent, and evaluating the application value of the SPT in the identification of ASD without global developmental delay (GDD) and developmental language disorder (DLD) is necessary. METHODS: A total of 200 children were selected as the research participants. There were 100 cases of ASD without GDD and 100 cases of DLD. All children were tested by SPT and Children Neuropsychological and Behavioral Scale-Revision (CNBS-R2016). Binomial logistic regression was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of SPT in identifying ASD without GDD and DLD. RESULTS: SPT equivalent age was lower than chronological age in the two groups, the difference between the ASD without GDD group was greater than that in the DLD group, and the proportion of SPT equivalent age retardation was higher than that in the DLD group; the differences were statistically significant. Logistic regression analysis showed that there was a difference in SPT equivalent age between DLD and ASD without GDD. When the cut-off value of the SPT was 8.5, the largest area under the ROC curve was 0.723, and the sensitivity and specificity for the diagnosis of ASD without GDD were 0.720 and 0.620 respectively. CONCLUSIONS: Symbolic play ability in ASD children is worse than that of DLD children at comparable development levels. SPT may be helpful to distinguish ASD without GDD from children with DLD.

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8. Chenausky KV, Baas B, Stoeckel R, Brown T, Green JR, Runke C, Schimmenti L, Clark H. Comorbidity and Severity in Childhood Apraxia of Speech: A Retrospective Chart Review. J Speech Lang Hear Res;2023 (Mar 7);66(3):791-803.

PURPOSE: The purpose of this study was to investigate comorbidity prevalence and patterns in childhood apraxia of speech (CAS) and their relationship to severity. METHOD: In this retroactive cross-sectional study, medical records for 375 children with CAS (M (age) = 4;9 [years;months], SD = 2;9) were examined for comorbid conditions. The total number of comorbid conditions and the number of communication-related comorbidities were regressed on CAS severity as rated by speech-language pathologists during diagnosis. The relationship between CAS severity and the presence of four common comorbid conditions was also examined using ordinal or multinomial regressions. RESULTS: Overall, 83 children were classified with mild CAS; 35, with moderate CAS; and 257, with severe CAS. Only one child had no comorbidities. The average number of comorbid conditions was 8.4 (SD = 3.4), and the average number of communication-related comorbidities was 5.6 (SD = 2.2). Over 95% of children had comorbid expressive language impairment. Children with comorbid intellectual disability (78.1%), receptive language impairment (72.5%), and nonspeech apraxia (37.3%; including limb, nonspeech oromotor, and oculomotor apraxia) were significantly more likely to have severe CAS than children without these comorbidities. However, children with comorbid autism spectrum disorder (33.6%) were no more likely to have severe CAS than children without autism. CONCLUSIONS: Comorbidity appears to be the rule, rather than the exception, for children with CAS. Comorbid intellectual disability, receptive language impairment, and nonspeech apraxia confer additional risk for more severe forms of CAS. Findings are limited by being from a convenience sample of participants but inform future models of comorbidity. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22096622.

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9. Gehdu BK, Tsantani M, Press C, Gray K, Cook R. EXPRESS: Recognition of facial expressions in autism: effects of face masks and alexithymia. Q J Exp Psychol (Hove);2023 (Mar 5):17470218231163007.

It is often assumed that the recognition of facial expressions is impaired in autism. However, recent evidence suggests that reports of expression recognition difficulties in autistic participants may be attributable to co-occurring alexithymia – a trait associated with difficulties interpreting interoceptive and emotional states – not autism per se. Due to problems fixating on the eye-region, autistic individuals may be more reliant on information from the mouth region when judging facial expressions. As such, it may be easier to detect expression recognition deficits attributable to autism, not alexithymia, when participants are forced to base expression judgements on the eye-region alone. To test this possibility, we compared the ability of autistic participants (with and without high levels of alexithymia) and non-autistic controls to categorize facial expressions i) when the whole face was visible, and ii) when the lower portion of the face was covered with a surgical mask. High-alexithymic autistic participants showed clear evidence of expression recognition difficulties: they correctly categorised fewer expressions than non-autistic controls. In contrast, low-alexithymic autistic participants were unimpaired relative to non-autistic controls. The same pattern of results was seen when judging masked and unmasked expression stimuli. In sum, we find no evidence for an expression recognition deficit attributable to autism, in the absence of high levels of co-occurring alexithymia, either when participants judge whole-face stimuli or just the eye-region. These findings underscore the influence of co-occurring alexithymia on expression recognition in autism.

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10. Hocking DR, Sun X, Haebich K, Darke H, North KN, Vivanti G, Payne JM. Delineating Visual Habituation Profiles in Preschoolers with Neurofibromatosis Type 1 and Autism Spectrum Disorder: A Cross-Syndrome Study. J Autism Dev Disord;2023 (Mar 6)

Atypical habituation to repetitive information has been commonly reported in Autism Spectrum Disorder (ASD) but it is not yet clear whether similar abnormalities are present in Neurofibromatosis Type 1 (NF1). We employed a cross-syndrome design using a novel eye tracking paradigm to measure habituation in preschoolers with NF1, children with idiopathic ASD and typically developing (TD) children. Eye movements were recorded to examine fixation duration to simultaneously presented repeating and novel stimuli. Children with NF1 showed a bias for longer look durations to repeating stimuli at the expense of novel stimuli, and slower habituation in NF1 was associated with elevated ASD traits. These findings could indicate aberrant modulation of bottom-up attentional networks that interact with the emergence of ASD phenotypes.

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11. Hong D, Iakoucheva LM. Correction to: Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology. Transl Psychiatry;2023 (Mar 7);13(1):80.

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12. Jones A, Kang S, Shaffer RC, Erickson CA, Schmitt LM. Behavioral inflexibility in fragile X syndrome: Accounts from caregivers and self-advocates. Front Psychol;2023;14:1118652.

INTRODUCTION: Behavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one’s behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions. In addition to the individual and family impact, behavioral inflexibility is often recognized as a defining phenotype of FXS and appears to be specific to FXS when compared to other genetic forms of intellectual disability. Despite the pervasiveness and severity of behavioral inflexibility in FXS, there are limited measures that adequately assess behavioral inflexibility in FXS. METHODS: We conducted semi-structured virtual focus groups with 22 caregivers, 3 self-advocates, and 1 professional to gather key stakeholders’ perspectives on and experiences of inflexible behavior observed in FXS. Audio-recordings from focus groups were transcribed using NVivo, then verified and coded. Two trained professionals reviewed codes to extract primary themes. RESULTS: Six themes were extracted: (1) Intolerance of change, (2) Intolerance to uncertainty, (3) Repetitive interests and behaviors, (4) Family impact, (5) Change in behavior across the lifespan, and (6) Impact of the COVID pandemic. Our findings show common examples of these themes included intolerance to disruption to routine, perseverative questioning, watching the same things over and over, and caregivers having to extensively pre-plan for events. DISCUSSION: The purpose of the current study was to gain key stakeholders’ perspectives via focus groups to elicit information and understand patterns of inflexible behaviors in FXS, with the goal of developing a disorder-specific measure to accurately assess behavioral inflexibility across the lifespan and in response to treatment. We were able to capture several phenotypic examples of behavioral inflexibility in FXS as well as their impact on individuals with FXS and their families. The wealth of information gained through our study will aid in our next steps of item generation for measure development of Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability – Fragile X Syndrome (RIGID-FX).

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13. Kaman N, Ishak A, Muhammad J. Knowledge, attitudes, and associated factors of caregivers towards children with autism spectrum disorder in East Coast Peninsular Malaysia. PeerJ;2023;11:e14919.

BACKGROUND: Caregivers are directly involved in managing the daily basic needs of children with autism spectrum disorder (ASD). The knowledge and attitudes of these caregivers are important to achieving success in their roles. Thus, this study aimed to determine what constitutes good knowledge, attitudes, and associated factors among caregivers toward children with ASD. METHODS: A cross-sectional study was conducted among 128 caregivers of children with ASD in Kota Bharu, Kelantan from May to August 2020, using convenience sampling. Validated questionnaires were used to assess the knowledge and attitudes toward children with ASD. The data were analyzed using SPSS version 24. Descriptive statistics and simple and multiple logistic regression analyses were then performed. RESULTS: The response rate was 100%. The proportion of good knowledge and attitudes toward children with ASD among caregivers was 85.1% and 88.3%, respectively. Factors significantly associated with good knowledge were being female (OR (95% CI) 2.79 [0.99-7.90]) and ASD children being non-first-born children (OR (95% CI) 0.41 [0.15-1.12]). Factors significantly associated with good attitudes were age of 30 years and older (OR (95% CI) 0.13 [0.03-0.62]) and caregiver having other children with other types of learning difficulties (OR (95% CI) 0.15 [0.04, 0.52]). CONCLUSIONS: The proportion of caregivers with good knowledge of ASD and good attitudes toward children with ASD was high. The caregiver’s age and sex, the position of the ASD child among the siblings, and the presence of other types of learning disorders in the family need to be considered when managing children with ASD.

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14. Kantor J, Li J, Du J, Svobodová Z, Klugar M, Salehi-Pourmehr H, Hampton D, Smolíková M, Kantorová L, Marečková J, Zmeškalová D, Munn Z. Impact of educational and psychological interventions compared with standard care in college/university students with autism spectrum disorder: a systematic review protocol. JBI Evid Synth;2023 (Mar 6)

OBJECTIVE: This review will explore the impact of educational and psychological interventions on educational, social, behavioral, and mental health outcomes in students with autism spectrum disorder in tertiary education. INTRODUCTION: This systematic review will inform a new guideline on support for students with autism spectrum disorder in the tertiary education environment. These students face multiple educational, behavioral, social, and health-related problems that require effective interventions. INCLUSION CRITERIA: Participants are students with autism spectrum disorder in a tertiary education study program. Educational and psychological interventions will be included, such as accommodations, meta-cognitive and self-regulation training, psychological counseling, social skills training, and peer-mentoring/academic coaching. The comparator will be standard care. The study outcomes will include academic drop-out rates and evaluations, learning skills, social skills and social engagement, behavior, mental health (including anxiety, stress, and depression), and employment after graduation. This review will consider quantitative studies only. METHODS: A 3-step search strategy will be used to find both published and unpublished studies in MEDLINE, CINAHL, APA PsycINFO, SocINDEX, Web of Science, Clinical Trials, ProQuest Dissertations and Theses, Open Dissertations, ERIC, WHO ICRTP, and Google Scholar. There will be no date or language limitations. All stages of article screening, critical appraisal, and data extraction will be conducted by 2 independent reviewers with the resolution of any disagreements done via consensus or through a senior reviewer. If possible, the included studies will be pooled using meta-analysis. The degree of certainty of the evidence will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42022323554.

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15. Keller SM. The Importance of Integrated Care for Individuals With Intellectual and Developmental Disabilities. Compend Contin Educ Dent;2023 (Mar);44(3):166-168.

People with intellectual and developmental disabilities (IDDs) commonly have complex healthcare challenges. An IDD is a condition that is a result of an abnormality beginning during a person’s neurodevelopment, often occurring in utero but also possibly occurring up to age 18. Any injury or maldevelopment of the nervous system can often result in lifelong health complications in this population, including those involving intellect, language, motor skills, vision, hearing, swallowing, behavior, autism, seizures, digestion, and many other areas. Individuals with IDDs often have multiple health complications, and their care is usually provided by a number of different healthcare providers, including a primary care provider, various healthcare specialists who focus on their particular areas of concern, an oral health provider, and a behavioral specialist(s), if needed. The American Academy of Developmental Medicine and Dentistry appreciates that integrated care is essential to providing care to those with IDDs. The name of the organization itself includes both medical and dental aspects, and the organization’s guiding principles include the concepts of integrated care, person-centered and family-centered approaches, and a deep appreciation for the importance of values and inclusion in a community. Continuing to provide education and training to healthcare practitioners is a key to improving health outcomes for individuals with IDDs. Additionally, focusing on the importance of integrated care will ultimately lead to a reduction in health disparities and improve access to quality healthcare services.

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16. Kral TVE, O’Malley L, Johnson K, Benvenuti T, Chittams J, Quinn RJ, Thomas JG, Pinto-Martin JA, Levy SE, Kuschner ES. Effects of a mobile health nutrition intervention on dietary intake in children who have autism spectrum disorder. Front Pediatr;2023;11:1100436.

BACKGROUND: Children who have Autism Spectrum Disorder (ASD) show preferences for processed foods, such as salty and sugary snacks (SSS) and sugar-sweetened beverages (SSB), while healthier foods, such as fruits and vegetables (FV), are consumed less. Innovative tools are needed that can efficiently disseminate evidence-based interventions and engage autistic children to improve their diet. AIM: The aim of this 3-month randomized trial was to test the initial efficacy of a mobile health (mHealth) nutrition intervention on changing consumption of targeted healthy (FV) and less healthy foods/beverages (SSS, SSB) in children who have ASD, ages 6-10, who were picky eaters. METHODS: Thirty-eight parent-child dyads were randomly assigned to either an intervention (technology) group or a wait list control (education) group. The intervention included behavioral skills training, a high level of personalization for dietary goals, and involved parents as « agents of change. » Parents in the education group received general nutrition education and the dietary goals but did not receive skills training. Children’s intake was assessed at baseline and at 3 months using 24-hour dietary recalls. RESULTS: While there were no significant group-by-time interactions (P > 0.25) for any of the primary outcomes, we found a significant main effect of time for FV intake (P = 0.04) indicating that both groups consumed more FV at 3 months (2.58 ± 0.30 servings/day) than at baseline (2.17 ± 0.28 servings/day; P = 0.03). Children in the intervention group who consumed few FV at baseline and showed high engagement with the technology increased their FV intake by 1.5 servings/day (P < 0.01). Children's taste/smell sensitivity significantly predicted their FV intake (P = 0.0446); for each unit of lower taste/smell sensitivity (indicating greater sensory processing abnormalities), FV intake increased by 0.13 ± 0.1 servings/day. DISCUSSION: This mHealth intervention did not yield significant between-group differences for changing consumption of targeted foods/beverages. Only children who consumed few FV at baseline and highly engaged with the technology increased their FV intake at 3 months. Future research should test additional strategies to expand the intervention's impact on a wider range of foods while also reaching a broader group of children who have ASD. This trial was registered at clinicaltrials.gov as NCT03424811.Clinical Trial Registration: This study was registered at clinicaltrials.gov as NCT03424811.

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17. Leuning EM, van den Berk-Smeekens I, van Dongen-Boomsma M, Staal WG. Eye Movement Desensitization and Reprocessing in adolescents with autism; Efficacy on ASD symptoms and stress. Front Psychiatry;2023;14:981975.

INTRODUCTION: Eye Movement Desensitization and Reprocessing (EMDR) is a well-established and thoroughly researched treatment method for posttraumatic stress symptoms. When patients with an autism spectrum disorder (ASD) are treated with EMDR for their Posttraumatic Stress Disorder (PTSD), they sometimes report a decrease in the core symptoms of ASD. This explorative pre-post-follow up design study is designed to investigate whether EMDR with a focus on daily experienced stress, is effective in reducing ASD symptoms and stress in adolescents with ASD. METHODS: Twenty-one adolescents with ASD (age 12 to 19) were treated with ten sessions EMDR, focusing on events of daily experienced stress. RESULTS: No significant decrease of ASD symptoms was found on the total score of the Social Responsiveness Scale (SRS) as reported by caregivers from baseline to end measurement. However, there was a significant decrease on total caregivers SRS score comparing the baseline to the follow-up measurement. On two subscales, Social Awareness and Social Communication, a significant decrease was found from baseline to follow-up. On the subscales Social Motivation and Restricted Interests and Repetitive Behavior, no significant effects were found. On pre- and posttest scores of total ASD symptoms measured by the Autism Diagnostic Observation Schedule (ADOS-2), no significant effects were found. On the contrary, scores on self-reported Perceived Stress Scale (PSS) showed a significant decrease from baseline to follow-up. Also, 52% of adolescents showed a significant improvement of global clinical functioning at endpoint measurement on the Clinical Global Impression Improvement, rated by an independent child psychiatrist. DISCUSSION: In sum, these results of this uncontrolled study suggest a partial effect of EMDR in adolescents with ASD on ASD symptoms, rated by their caregivers. In addition, the results of this study show that EMDR treatment on daily experienced stress significantly reduce perceived stress as reported by the participants, and improves global clinical functioning. The results also suggest a ‘sleeper effect’, since no significant effects were found between baseline- and post- treatment measurements, but only between baseline- and follow up three months after the treatment. This finding is in line with other studies investigating psychotherapeutic effects in ASD. Implications for clinical practice and suggestions for future research are discussed.

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18. Lin CW, Ellegood J, Tamada K, Miura I, Konda M, Takeshita K, Atarashi K, Lerch JP, Wakana S, McHugh TJ, Takumi T. An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development. Mol Psychiatry;2023 (Mar 7)

The BTBR T(+)Itpr3(tf)/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.

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19. Magán-Maganto M, Canal-Bedia R, Bejarano-Martín Á, Martín-Cilleros MV, Hernández-Fabián A, Calvarro-Castañeda AL, Roeyers H, Jenaro-Río C, Posada de la Paz M. Predictors of autism spectrum disorder diagnosis in a spanish sample of preterm children with very low birthweight: A cross-sectional study. Health Sci Rep;2023 (Mar);6(3):e1143.

BACKGROUND AND AIMS: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a higher likelihood of being diagnosed in preterm populations. Likewise, low birthweight has also been connected with an increased likelihood of ASD. The objectives were to study the frequency and define the relationship between ASD, gestational age, birthweight, and growth percentiles for preterm children. METHODS: A sample of preterm children with very low birthweight was selected from the Spanish population at 7-10 years old. Families were contacted from the hospital, and they were offered an appointment to conduct a neuropsychological assessment. The children who showed signs of ASD were referred to the diagnostic unit for differential diagnosis. RESULTS: A total of 57 children completed full assessments, with 4 confirmed ASD diagnoses. The estimated prevalence was 7.02%. There were statistically significant weak correlations between ASD and gestational age (τb = -0.23), and birthweight (τb = -0.25), suggesting there is a higher likelihood of developing ASD for those born smaller or earlier in their gestation. CONCLUSION: These results could improve ASD detection and outcomes for this vulnerable population while also supporting and enhancing previous findings.

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20. Miller K, Day PL, Behl S, Stromback L, Delgado A, Jannetto PJ, Wieser ME, Mehta SQ, Pandey MK. Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America. Front Mol Neurosci;2023;16:1133218.

To better understand zinc and copper regulation and their involvement in various biochemical pathways as it relates to autism spectrum disorder (ASD), isotopic composition of serum zinc and copper were evaluated in both healthy children and children with ASD in North America. No significant difference in isotopic composition of serum zinc or copper with respect to healthy controls and ASD children were identified. However, the isotopic composition of serum copper in boys was found to be enriched in (65)Cu in comparison to previously published healthy adult copper isotopic composition. Furthermore, in both boys and girls, the average isotopic composition of serum zinc is heavier than previously published healthy adult isotopic zinc composition. There was also a negative association between total zinc concentrations in serum and the zinc isotopic composition of serum in boys. Finally, children with heavier isotopic composition of copper also showed a high degree of variability in their zinc isotopic composition. While numerous studies have measured the isotopic composition of serum zinc and copper in adults, this is one of the first studies which measured the isotopic composition of serum copper and zinc in children, specifically those diagnosed with ASD. The results of this study showed that age and gender specific normal ranges of isotopic composition must be established to effectively use isotopic composition analysis in studying various diseases including ASD.

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21. Munn EE, Lang D, Hynes J, Northcutt A, Patten B, Wadsworth DD, Pangelinan MM. The Effects of Virtual Zumba on Functional Outcomes in Adults with Developmental Disabilities. Med Sci Sports Exerc;2023 (Feb 24)

INTRODUCTION: Few studies have examined the comprehensive impact of adaptive exercise interventions across multiple functional domains (i.e., physical and cognitive health) in adults with developmental disabilities (DD). METHODS: The present study examined the effects of a 10-week (2 session/week, 1 hour/session) adapted Zumba® intervention on the 6-Minute Walk Test (6-MWT), Timed Up and Go (TUG), Clinical Test of Sensory Interaction on Balance, body composition, and executive function in 44 adults with DD ages 20.8-69.2 years. In addition to examining overall differences between control and intervention conditions, the effects of different Zumba® tempos (normal/low) were examined. A cross-over design with a 3-month wash-out period was employed such that participants in the intervention also served as controls. The participants were quasi-randomized into one of two Zumba® conditions: low tempo Zumba® (0.75 normal speed; n = 23) and normal tempo Zumba® (n = 21). RESULTS: A significant Condition x Time interaction was observed for the 6-MWT and TUG; participants in the low and normal tempo Zumba® conditions significantly increased the distance walked for the 6-MWT and reduced the total time for the TUG. No improvement was observed during the control condition for these measures. There were no significant Condition x Time interactions for the other outcomes. CONCLUSIONS: These findings have implications on the efficacy and implementation of virtual Zumba® programs to increase abilities related to independent performance of activities of daily living in adults with disabilities.

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22. Olusanya BO, Gulati S, Newton CRJ. The Nurturing Care Framework and Children With Developmental Disabilities in LMICs. Pediatrics;2023 (Mar 7)

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23. Pang RCC, Ho MSH, Wong PWC. A Review of the Literature on the Multiple Forms of Stigmatization of Caregivers of Children with Autism Among Ethnic Minority Groups. J Racial Ethn Health Disparities;2023 (Mar 6)

Multiple forms of stigmatization are experienced by caregivers of children with autism among ethnic minority (EM) groups in various countries. Such forms of stigmatization can lead to delayed assessment and services for mental health among children and caregivers. This review identified the research literature on the types of stigmatization experienced by caregivers of children with autism with an EM background. A total of 19 studies published after 2010 (i.e., 12 from the USA, 2 from the UK, 1 from Canada, and 1 from New Zealand) of caregivers of 20 ethnicities were identified and reviewed, and their reporting qualities systematically also assessed. Four main themes: (1) self-stigma, (2) social stigma, (3) stigma towards EM parents of children on the autism spectrum, and (4) service utilization stigma, and nine sub-themes were identified. The discrimination experienced by caregivers were extracted, synthesized, and further discussed. While the reporting quality of the studies included is good, the depth of the understanding of this under-researched yet important phenomenon is very limited. The multiple forms of stigmatization experiences are complex, and it may be difficult to disentangle whether the causes of stigmatization were autism and/or EM related, and the types of stigmatization can vary enormously among different ethnic groups in different societies. More quantitative studies are needed to quantify the impacts of multiple forms of stigmatization on families of children with autism in EM groups so that more socially inclusive support for caregivers with an EM background in host countries can be developed.

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24. Pirinen V, Loukusa S, Dindar K, Mäkinen L, Hurtig T, Jussila K, Mattila ML, Eggers K. A Comprehensive Analysis of Speech Disfluencies in Autistic Young Adults and Control Young Adults: Group Differences in Typical, Stuttering-Like, and Atypical Disfluencies. J Speech Lang Hear Res;2023 (Mar 7);66(3):832-848.

PURPOSE: The purpose of this study was to examine the nature of speech disfluencies in autistic young adults and controls by using a wide-range disfluency classification of typical disfluencies (TD; i.e., filled pauses, revisions, abandoned utterances, and multisyllable word and phrase repetitions), stuttering-like disfluencies (SLD; i.e., sound and syllable repetitions, monosyllable word repetitions, prolongations, blocks, and broken words), and atypical disfluencies (AD; i.e., word-final prolongations and repetitions and atypical insertions). METHOD: Thirty-two autistic young adults and 35 controls completed a narrative telling task based on socially complex events. Frequencies of total disfluencies, TD, SLD, AD and stuttering severity were compared between groups. RESULTS: The overall frequency of disfluencies was significantly higher in the autistic group and significant between-group differences were found for all disfluency categories. The autistic group produced significantly more revisions, filled pauses, and abandoned utterances, and each subtype of SLD and AD than the control group. In total, approximately every fourth autistic participants scored at least a very mild severity of stuttering, and every fifth produced more than three SLD per 100 syllables. CONCLUSIONS: Disfluent speech can be challenging for effective communication. This study revealed that the speech of autistic young adults was highly more disfluent than that of the controls. The findings provide information on speech disfluency characteristics in autistic young adults and highlight the importance of evaluating speech disfluency with a wide-range disfluency classification in autistic persons in order to understand their role in overall communication. The results of this study offer tools for SLPs to evaluate and understand the nature of disfluencies in autistic persons.

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25. Sato J, Safar K, Vogan VM, Taylor MJ. Functional connectivity changes during working memory in autism spectrum disorder: A two-year longitudinal MEG study. Neuroimage Clin;2023 (Mar 2);37:103364.

Working memory impairments have been reported in adults with autism spectrum disorder (ASD) and associated with functional outcomes and social difficulties. However, little is known about the developmental trajectory of working memory in youth with ASD. The current magnetoencephalography (MEG) study is the first to examine the longitudinal development over two years of working memory networks in youth with ASD. We analysed MEG data from 32 children and adolescents with and without ASD (64 datasets; 7-14 years), all tested twice at a two-year interval, during a visual n-back task, with two loads (1- and 2-back). We performed a whole-brain functional connectivity analysis to examine the networks during the successful recognition of visual stimuli. We demonstrate that youth with ASD show decreased connectivity in the theta frequency (4-7 Hz) in the higher memory load (2-back) condition compared to typically developing (TD) controls. This hypo-connected theta network was anchored in primary visual areas with connections to frontal, parietal and limbic regions. These network differences were found despite similar task performance between ASD and TD groups. Within the TD group, we found an increase in alpha (8-14 Hz) connectivity at Time 2 compared to Time 1 in both the 1- and 2-back conditions. These findings demonstrate the continued development of working memory mechanisms over middle childhood, which were not apparent in youth with ASD. Together, our findings support a network-based approach to understanding atypical neural functioning in ASD and the developmental trajectories of working memory processes over middle childhood.

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26. Sawicki CM, Pielech M, Wade SD. Practice Patterns Among Dentist Anesthesiologists for Pediatric Patients with Autism Spectrum Disorders. Pediatr Dent;2023 (Jan 15);45(1):37-53.

PURPOSE: The purpose of this study was to evaluate practice patterns among dentist anesthesiologists for pediatric patients with autism spectrum disorders (ASD) undergoing sedation for dental procedures. METHODS: An electronic nationwide survey was delivered to all members of the American Society of Dentist Anesthesiologists. The survey assessed provider training and comfort in treating pediatric patients with ASD, perioperative procedures for children with and without ASD, and preferred educational resources for the perioperative management of pediatric patients with ASD. RESULTS: Respondents were 114 dentist anesthesiologists and residents (33.3 percent response rate). Respondents indicated a high comfort level for managing pediatric patients with ASD for sedation (mean equals 91.9±14.74 [SD] percent). The average number of patients with ASD who respondents treat per week was 3.48±2.44). Providers reported making scheduling and staffing accommodations for patients with ASD. More than half of respondents reported no difference between patient groups in medication dosing for sedation and medication regimens used intraoperatively; however, only 43.9 percent of providers indicated using equivalent preoperative medication regimens for both patient groups, and providers reported increased usage of preoperative anxiolytic techniques with patients with ASD. Importantly, 87.7 percent of respondents reported the same incidence of adverse events during the perioperative period between groups. CONCLUSIONS: Findings from this survey suggest there are both similarities and differences in how dentist anesthesiologists practice with pediatric patients with and without autism spectrum disorders. Additional research is warranted to measure the clinical benefits of modified practices for patients with ASD and identify best practices for this vulnerable population.

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27. Shakya S, Parsekar SS, Ramachandran S, Madapura SS, Balakrishna Shetty H, Anaby D, Gopalakrishna S, Venkatesan VS, Rao BK. Physiotherapy interventions for head and trunk control in children with developmental disabilities: A scoping review protocol. F1000Res;2022;11:1074.

Background: Head and trunk control is prerequisite skill that maximizes engagement and participation in one’s environment by integrating vision, oromotor skill, arm control and respiration. Various physiotherapy and technology-based interventions have been utilized to facilitate head and trunk control in children with developmental disabilities. This scoping review is planned to map and summarize existing studies from the scientific literature on physiotherapy and technology-based interventions for head and trunk control in children with developmental disabilities. Methods: The scoping review will utilize the Joanna Briggs Institute scoping review methodology. The review will cover studies including children and adolescents aged between two years and 17 years 11 months 29 days, with developmental disabilities where in child finds difficulty aligning head and trunk in sitting position, against gravity, for more than a minute. We will include randomized controlled trial (RCT), non-RCT, quasi-experimental trial, and systematic reviews that have employed physiotherapy and technology-based interventions. Database-specific search strategy will be used to search records in Medline (PubMed and Web of Science), Embase, Scopus, CINAHL, PEDro, and Cochrane Library. Additionally, various grey literatures and clinical-trial registries will be searched. Two reviewers, independently, will screen and extract the data. Tables and visual representations will be utilized to present the extracted data. Registration details: The protocol has been registered in Open Science Framework, DOI: 10.17605/OSF.IO/B3RSU (22 (nd) August 2022).

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28. Sharkey RJ, Nickl-Jockschat T. The neurobiology of autism spectrum disorder as it relates to twice exceptionality. Neurobiol Learn Mem;2023 (Mar 7);200:107740.

There is a long-standing association between exceptional cognitive abilities of various sorts and neuropsychiatric illness, but it has historically largely been investigated in an exploratory and non-systematic way. One group in which this association has been investigated with more rigor is in subjects who have been identified as twice exceptional; an educational term describing subjects who are both gifted and diagnosed with a neuropsychiatric disorder. This term covers multiple conditions, but is of specific interest in particular in the study of autism spectrum disorder. Recent findings have led to the development of a hypothesis that a certain degree of the neurobiology associated with autism might even be advantageous for individuals and could lead to high giftedness, while becoming disadvantageous, once a certain threshold is surpassed. In this model, the same neurobiological mechanisms confer an increasing advantage up to a certain threshold, but become pathological past that point. Twice-exceptional individuals would be exactly at the inflection point, being highly gifted, but also symptomatic at the same time. Here, we review how existing neuroimaging literature on autism spectrum disorder can inform research on twice exceptionality specifically. We propose to study key neural networks with a robust implication in ASD to identify the neurobiology underlying twice-exceptionality. A better understanding of the neural mechanisms of twice exceptionality should help to better understand resilience and vulnerability to neurodevelopmental disorders and to. further support affected individuals.

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29. Straiton D, Frost K, Ingersoll B. Factors that influence clinical decisions about offering parent coaching for autistic youth served within the Medicaid system. Implement Res Pract;2023 (Jan-Dec);4

BACKGROUND: Parent coaching is an evidence-based practice for young autistic children, but it is underutilized in lower-resourced community settings like the Medicaid system (Straiton et al., 2021b). Clinicians often struggle to implement parent coaching with low-income and marginalized families (Tomczuk et al., 2022), but little is known about which factors influence clinician decision making processes about providing parent coaching to this population. METHODS: This qualitative analysis used the framework method and thematic analysis. We used the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework (Aarons et al., 2011) to identify factors in the clinical decision-making process that community providers use when offering parent coaching to families of Medicaid-enrolled autistic children. Interviews with 13 providers and a focus group with 13 providers were analyzed. RESULTS: The following themes emerged: 1) Policies drive provider task priorities and affect competing demands; 2) Providers are more likely to use parent coaching when agency leaders monitor parent coaching benchmarks, though this is rarely done; 3) Logistical factors like scheduling and treatment location affect perceived feasibility of using parent coaching; 4) Previous experience or coursework in parent coaching and/or family systems supports the quality of parent coaching implementation; 5) Provider perceptions of « parent readiness » are initially indicated by overt expressions of parent interest. CONCLUSIONS: In the absence of outer-context and inner-context policies, providers have more decision-making power to offer parent coaching based on their own judgements and preferences, which may result in fewer families being offered parent coaching and increased bias related to which families are offered this service. State-, agency-, and clinician-level recommendations are provided for increasing equitable provision of this evidence-based practice for autism.

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30. Straub D, Schmitt LM, Boggs AE, Horn PS, Dominick KC, Gross C, Erickson CA. A sensitive and reproducible qRT-PCR assay detects physiological relevant trace levels of FMR1 mRNA in individuals with Fragile X syndrome. Sci Rep;2023 (Mar 7);13(1):3808.

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS is caused by a trinucleotide repeat expansion in the 5′ untranslated region of the FMR1 gene, which leads to gene methylation, transcriptional silencing, and lack of expression of Fragile X Messenger Riboprotein (FMRP). Currently available FXS therapies are inefficient, and the disease severity is highly variable, making it difficult to predict disease trajectory and treatment response. We and others have recently shown that a subset of full-mutation, fully-methylated (FM-FM) males with FXS express low amounts of FMRP which could contribute to phenotypic variability. To better understand the underlying mechanisms, we developed a sensitive qRT-PCR assay to detect FMR1 mRNA in blood. This assay reproducibly detects trace amounts of FMR1 mRNA in a subset of FM-FM males, suggesting that current Southern Blot and PCR determination of FM-FM status is not always associated with complete transcriptional silencing. The functional relevance of trace-level FMR1 mRNA is confirmed by showing a positive correlation with cognitive function; however, phenotypic variability is not fully explained by FMR1 expression. These results corroborate the need for better molecular assays for FXS diagnosis and encourage studies to elucidate the factors contributing to the phenotypic variability of FXS.

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31. Taels L, Feyaerts J, Lizon M, De Smet M, Vanheule S. ‘I felt like my senses were under attack’: An interpretative phenomenological analysis of experiences of hypersensitivity in autistic individuals. Autism;2023 (Mar 6):13623613231158182.

Research shows that the way autistic individuals perceive and process sensory stimuli differs from those of non-autistic people. However, while current research often focuses on what sensory differences in autism are and which neurocognitive processes may explain these, it often does not explicitly address what it is like to experience the world through the senses of an autistic person. To explore this understudied dimension, we conducted 18 in-depth interviews with autistic individuals in order to better understand how they personally experienced hypersensitivity from a first-person perspective. Participants described hypersensitivity as a feeling of being bombarded by intrusive stimuli that seemed to invade their bodies and from which they had difficulties distancing themselves. They also indicated how due to hypersensitivity they often perceived their (social) environment as invasive, chaotic, unpredictable or threatening. Hypersensitivities were thus not only described as unsettling bodily experiences but also related to challenges in perceiving, understanding and interacting with the (social) world. By focussing on the subjective dimension of sensory processing in autism, our study thus highlights how sensory difficulties are not peripheral features of autism but play an essential part in the daily challenges faced by autistic individuals.

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32. Tsuji M, Mukai T, Sato Y, Azuma Y, Yamamoto S, Cayetanot F, Bodineau L, Onoda A, Nagamura-Inoue T, Coq JO. Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight. Sci Rep;2023 (Mar 7);13(1):3841.

Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attention-deficit/hyperactive disorder and autism spectrum disorder, as well as cerebral palsy, for which no prophylactic measure exists. Neuroinflammation in fetuses and neonates plays a major pathogenic role in NDDs. Meanwhile, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) exhibit immunomodulatory properties. Therefore, we hypothesized that systemic administration of UC-MSCs in the early postnatal period may attenuate neuroinflammation and thereby prevent the emergence of NDDs. The LBW pups born to dams subjected to mild intrauterine hypoperfusion exhibited a significantly lesser decrease in the monosynaptic response with increased frequency of stimulation to the spinal cord preparation from postnatal day 4 (P4) to P6, suggesting hyperexcitability, which was improved by intravenous administration of human UC-MSCs (1 × 10(5) cells) on P1. Three-chamber sociability tests at adolescence revealed that only LBW males exhibited disturbed sociability, which tended to be ameliorated by UC-MSC treatment. Other parameters, including those determined via open-field tests, were not significantly improved by UC-MSC treatment. Serum or cerebrospinal fluid levels of pro-inflammatory cytokines were not elevated in the LBW pups, and UC-MSC treatment did not decrease these levels. In conclusion, although UC-MSC treatment prevents hyperexcitability in LBW pups, beneficial effects for NDDs are marginal.

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33. Xu XJ, Lang JD, Yang J, Long B, Liu XD, Zeng XF, Tian G, You X. Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study. Front Immunol;2023;14:1100816.

BACKGROUND: Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD. METHODS: A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features. RESULTS: The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups. CONCLUSIONS: Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.

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34. Yuan B, Wang M, Wu X, Cheng P, Zhang R, Yu S, Zhang J, Du Y, Wang X, Qiu Z. Identification of de novo Mutations in the Chinese Autism Spectrum Disorder Cohort via Whole-Exome Sequencing Unveils Brain Regions Implicated in Autism. Neurosci Bull;2023 (Mar 7)

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation and transcriptional regulation, have been identified through human genetic studies, the East Asian ASD cohorts are still under-represented in genome-wide genetic studies. Here, we applied whole-exome sequencing to 369 ASD trios including probands and unaffected parents of Chinese origin. Using a joint-calling analytical pipeline based on GATK toolkits, we identified numerous de novo mutations including 55 high-impact variants and 165 moderate-impact variants, as well as de novo copy number variations containing known ASD-related genes. Importantly, combined with single-cell sequencing data from the developing human brain, we found that the expression of genes with de novo mutations was specifically enriched in the pre-, post-central gyrus (PRC, PC) and banks of the superior temporal (BST) regions in the human brain. By further analyzing the brain imaging data with ASD and healthy controls, we found that the gray volume of the right BST in ASD patients was significantly decreased compared to healthy controls, suggesting the potential structural deficits associated with ASD. Finally, we found a decrease in the seed-based functional connectivity between BST/PC/PRC and sensory areas, the insula, as well as the frontal lobes in ASD patients. This work indicated that combinatorial analysis with genome-wide screening, single-cell sequencing, and brain imaging data reveal the brain regions contributing to the etiology of ASD.

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35. Zhang P, Omanska A, Ander BP, Gandal MJ, Stamova B, Schumann CM. Neuron-specific transcriptomic signatures indicate neuroinflammation and altered neuronal activity in ASD temporal cortex. Proc Natl Acad Sci U S A;2023 (Mar 7);120(10):e2206758120.

Autism spectrum disorder (ASD) is a highly heterogeneous disorder, yet transcriptomic profiling of bulk brain tissue has identified substantial convergence among dysregulated genes and pathways in ASD. However, this approach lacks cell-specific resolution. We performed comprehensive transcriptomic analyses on bulk tissue and laser-capture microdissected (LCM) neurons from 59 postmortem human brains (27 ASD and 32 controls) in the superior temporal gyrus (STG) of individuals ranging from 2 to 73 years of age. In bulk tissue, synaptic signaling, heat shock protein-related pathways, and RNA splicing were significantly altered in ASD. There was age-dependent dysregulation of genes involved in gamma aminobutyric acid (GABA) (GAD1 and GAD2) and glutamate (SLC38A1) signaling pathways. In LCM neurons, AP-1-mediated neuroinflammation and insulin/IGF-1 signaling pathways were upregulated in ASD, while mitochondrial function, ribosome, and spliceosome components were downregulated. GABA synthesizing enzymes GAD1 and GAD2 were both downregulated in ASD neurons. Mechanistic modeling suggested a direct link between inflammation and ASD in neurons, and prioritized inflammation-associated genes for future study. Alterations in small nucleolar RNAs (snoRNAs) associated with splicing events suggested interplay between snoRNA dysregulation and splicing disruption in neurons of individuals with ASD. Our findings supported the fundamental hypothesis of altered neuronal communication in ASD, demonstrated that inflammation was elevated at least in part in ASD neurons, and may reveal windows of opportunity for biotherapeutics to target the trajectory of gene expression and clinical manifestation of ASD throughout the human lifespan.

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36. Zhao PY, Yao RQ, Zheng LY, Wu Y, Li YX, Dong N, Li JY, Du XH, Yao YM. Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis. Burns Trauma;2023;11:tkac055.

BACKGROUND: Ribophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular homeostasis. Whether ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy (ERphagy) and mitophagy remains unclear. This study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte apoptosis. METHODS: The activity and regulation of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting, laser confocal microscopy and transmission electron microscopy. Then, we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic challenge. RESULTS: Both cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy, which peaked at 24 h. When NUFIP1 was knocked down, T-lymphocyte apoptosis was noticeably increased. Conversely, the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte apoptosis. Consistently, the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type mice. In addition, the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway, and PERK-ATF4-CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of sepsis. CONCLUSIONS: NUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK-ATF4-CHOP pathway in the context of sepsis. Thus, targeting NUFIP1-mediated ribophagy might be of importance in reversing the immunosuppression associated with septic complications.

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37. Zhao Y, Luo Y, Zhang R, Zheng X. Direct and indirect costs for families of children with autism spectrum disorder in China. Autism;2023 (Mar 7):13623613231158862.

This is the first comprehensive national study to explore the direct and indirect costs for families of children with autism spectrum disorder in China. The increasing prevalence of autism spectrum disorder highlights a growing need for resources to provide care for families of children with autism spectrum disorder. The medical and nonmedical costs and parents’ productivity loss have caused a serious burden on their families. Our objective is to estimate the direct and indirect costs for the families of children with autism spectrum disorder in China. The target population was parents of children with autism spectrum disorder. We analyzed the costs using cross-sectional data from a Chinese national family survey with children aged 2-6 years (N = 3236) who were clinically diagnosed with autism spectrum disorder. Family data from 30 provinces in China were obtained. Cost items included direct medical costs, direct nonmedical costs, and indirect costs. In this study, we found that the largest part of family costs for autism spectrum disorder are nonmedical costs and productivity loss. Autism spectrum disorder has imposed a huge economic burden on parents having children with autism spectrum disorder in China, who need more support than the current health care system provides.

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