1. Alasiri RM, Albarrak DA, Alghaith DM, Alsayari OS, Alqahtani YS, Bafarat AY, Tashkandi NF. Quality of Life of Autistic Children and Supported Programs in Saudi Arabia: A Cross-Sectional Study. Cureus;2024 (Jan);16(1):e51645.

BACKGROUND: Autism spectrum disorder (ASD) is a neurobehavioral condition marked by social interaction challenges, communication deficits, and repetitive behaviors, with studies in Saudi Arabia showing varying prevalence rates in different regions. This study aimed to evaluate the social context of autistic children and the quality of life (QOL) for families of children with autism utilizing the Beach Center Family Quality of Life Scale (BCFQOL). METHODS: This cross-sectional study, conducted at King Abdulaziz Medical City in Saudi Arabia over a six-month period, included ASD children aged 1-14 years. The QOL was measured using the BCFQOL scale for families. Data were analyzed using the Jamovi software (Windows version 2.4.1, the Jamovi Project, retrieved from https://www.jamovi.org). RESULTS: A total of 102 responses were collected in the study. The overall satisfaction score was 93.6±16.6 out of 125, with 85.3% of participants expressing satisfaction. Domains explored included family interaction (23.8±5.29 out of 30), parenting practices (23.9±3.83 out of 30), emotional well-being (13.1±4.16 out of 20), physical and material well-being (18.7±4.24 out of 25), and disability-related support (14.2±4.0 out of 20). In terms of specific sociodemographic factors, no statistically significant differences in satisfaction were observed across various categories. CONCLUSION: Families of children with ASD in Saudi Arabia generally report high levels of satisfaction, as assessed by the BCFQOL. The study covered various domains, including family interaction, parenting practices, emotional well-being, physical well-being, and disability-related support, with most respondents expressing satisfaction in these areas. Notably, sociodemographic factors did not significantly influence satisfaction levels, underscoring the pervasive nature of the findings across different demographic groups. Further studies with a larger sample size and a longer follow-up period are required to validate these findings.

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2. Amodeo L, Goris J, Nijhof AD, Wiersema JR. Electrophysiological correlates of self-related processing in adults with autism. Cogn Affect Behav Neurosci;2024 (Feb 5)

The term « self-bias » refers to the human propensity to prioritize self- over other-related stimuli and is believed to influence various stages of the processing stream. By means of event-related potentials (ERPs), it was recently shown that the self-bias in a shape-label matching task modulates early as well as later phases of information processing in neurotypicals. Recent claims suggest autism-related deficits to specifically impact later stages of self-related processing; however, it is unclear whether these claims hold based on current findings. Using the shape-label matching task while recording ERPs in individuals with autism can clarify which stage of self-related processing is specifically affected in this condition. Therefore, this study sought to investigate the temporal course of self-related processing in adults with and without autism. Thirty-two adults with autism and 27 neurotypicals completed a shape-label matching task while ERPs were concomitantly recorded. At the behavioral level, results furnished evidence for a comparable self-bias across groups, with no differences in task performance between adults with and without autism. At the ERP level, the two groups showed a similar self-bias at early stages of self-related information processing (the N1 component). Conversely, the autism group manifested a lessened differentiation between self- and other-related stimuli at later stages (the parietal P3 component). In line with recent claims of later phases of self-related processing being altered in autism, we found an equivalent self-bias between groups at an early, sensory stage of processing, yet a strongly diminished self-bias at a later, cognitive stage in adults with autism.

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3. Anastasescu CM, Stoicănescu E, Badea O, Popescu F. Micronutrient Research in Autism Spectrum Disorder. A Clinical Study. Curr Health Sci J;2023 (Jul-Sep);49(3):409-415.

Autistic spectrum disorders are part of the category of neurodevelopmental disorders, characterized by: difficulties in communication and social interaction, restrictive and repetitive patterns of behaviours and activities, which are present throughout the developmental period, and can be diagnosed in the first five years of life. Due to the increase in the incidence of this disorder in recent years, it has become a topic of great interest both to specialists in child and adolescent psychiatry and to researchers in the field. Given the polymorphism of Autism Spectrum Disorder and the need to discover factors that better explain the etiology of this disorder, studies related to biomarkers are extremely varied. One of the areas of study that have exercised particular interest is related to the involvement of metals in the pathology of autism spectrum disorder. Apart from the controversies related to heavy metals that according to studies affect the developmental process, there are studies that suggest that some micronutrients such as zinc, copper, selenium, iron, magnesium, may be involved in the etiology of autism spectrum disorder. Starting from these studies, we set out to investigate to what extent these essential metals for the body are involved in the etiology of autism spectrum disorder and how they influence the severity of symptoms.

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4. Appah J, Senoo-Dogbey VE, Armah D, Wuaku DA, Ohene LA. A qualitative enquiry into the challenging roles of caregivers caring for children with Autism Spectrum Disorders in Ghana. J Pediatr Nurs;2024 (Feb 5);76:23-29.

BACKGROUND: Autism Spectrum Disorder (ASD) is a condition commonly characterized by challenges with social interaction, repetitive atypical behaviour, and restricted interest. It is estimated that about 1 in 160 children has ASD. Caring for children with ASD is challenging for many parents or caregivers. OBJECTIVES: The study aims at exploring the challenges experienced by caregivers of children with ASD. METHODS: A qualitative phenomenological study was employed using an exploratory descriptive research design. A total of 10 participants were recruited in this study using a purposive sampling technique. Data were analysed using content analysis procedures. RESULT: Caregivers of children with ASD face social, financial, and emotional challenges, challenges in accessing health care, education and training of their children in mainstream school settings. CONCLUSION: The numerous challenges have implications for the quality of life of the caregivers and their children. The financial challenges and inaccessibility of specialist health services have serious implications for the continuous medical care and monitoring of children with ASD. The challenges in education and training of children with ASD has negative consequences for enrolment and retention of children with ASD in mainstream school settings.

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5. Cage E, Crompton CJ, Dantas S, Strachan K, Birch R, Robinson M, Morgan-Appel S, MacKenzie-Nash C, Gallagher A, Botha M. What are the autism research priorities of autistic adults in Scotland?. Autism;2024 (Feb 4):13623613231222656.

Although research has the potential to improve autistic people’s lives, lots of funding goes towards research looking at topics which autistic people say has little impact in their everyday lives. Autistic people’s lives can be different depending on where they live, and Scotland is a unique country in many ways. We wanted to find out which topics autistic people in Scotland want to see research on. Our team of autistic and non-autistic researchers (including university-based and community researchers) created a survey where 225 autistic adults rated and ranked the importance of possible research topics and shared their thoughts on what topics mattered to them. The five most important topics were mental health and well-being, identifying and diagnosing autistic people, support services (including healthcare and social care), non-autistic people’s knowledge and attitudes and issues impacting autistic women. The three least important topics were genetics or biological aspects of autism, autism treatments/interventions and causes of autism. Our findings indicate that autistic people in Scotland want research to focus on things that matter to their day-to-day lives. Also, the Scottish government says they will be listening to autistic people in their latest policy plans, and we believe that considering autistic people’s research priorities is an important part of this. Our findings also add to growing calls for change to happen in how and what autism researchers do research on.

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6. Carpita B, Nardi B, Bonelli C, Massimetti E, Amatori G, Cremone IM, Pini S, Dell’Osso L. Presence and correlates of autistic traits among patients with social anxiety disorder. Front Psychiatry;2023;14:1320558.

INTRODUCTION: Due to their similar behavioral presentation, it can sometimes be challenging to distinguish between a social anxiety disorder (SAD) and the social avoidance that is frequently described in autism spectrum disorder (ASD). Moreover, a growing body of evidences is reporting that a significant proportion of subjects with ASD also meet the requirements for SAD and, vice versa, subjects with SAD tend to exhibit a higher prevalence of autistic traits. AIM: In this framework, the current study aims to evaluate prevalence and correlates of autistic traits in a sample of adult subjects diagnosed with SAD and healthy controls (HC), also evaluating which autism spectrum dimensions may statistically predict higher SAD symptoms. METHODS: 56 subjects with a clinical diagnosis of SAD and 56 gender and age matched HC were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, the Social Anxiety Spectrum – Short Version (SHY- SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). RESULTS: SAD group scored significantly higher in all AdAS Spectrum and SHY-SV domains and total score compared to the HC group with no significant gender difference. SHY-SV total and domain scores, were strongly and positively and strongly correlated with all AdAS Spectrum domains and total score. AdAS Spectrum total score and Childhood/Adolescence, Non-Verbal Communication, Empathy and Restricted interests and Rumination domain scores score were significant predictors of higher SHY-SV score. CONCLUSION: Our results confirm the link between SAD and autistic traits also in adult population, describing not only high levels of autistic traits in SAD adults, but also significant correlations between many core features of the two disorders and a predictive role of autistic traits on higher SAD symptoms.

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7. Chung H, Wilkinson CL, Job Said A, Tager-Flusberg H, Nelson CA. Evaluating early EEG correlates of restricted and repetitive behaviors for toddlers with or without autism. Res Sq;2024 (Jan 18)

BACKGROUND: Restricted and repetitive behaviors (RRB) are among the primary characteristics of autism spectrum disorder (ASD). Despite the potential impact on later developmental outcomes, our understanding of the neural underpinnings of RRBs is limited. Alterations in EEG alpha activity have been observed in ASD and implicated in RRBs, however, developmental changes within the alpha band requires careful methodological considerations when studying its role in brain-behavior relationships during infancy and early childhood. Novel approaches now enable the parameterization of the power spectrum into periodic and aperiodic components. This study aimed to characterize the neural correlates of RRBs in infancy by (1) comparing infant resting-state measures (periodic alpha and aperiodic activity) between infants who develop ASD, elevated likelihood infants without ASD, and low likelihood infants without ASD, and (2) evaluate whether these infant EEG measures are associated with frequency of RRBs measured at 24 months. METHODS: Baseline non-task related EEG data were collected from 12-to-14-month-old infants with and without elevated likelihood of autism (N=160), and periodic alpha activity (periodic alpha power, individual peak alpha frequency and amplitude), and aperiodic activity measures (aperiodic exponent) were calculated. Parent-reported RRBs were obtained at 24 months using the Repetitive Behavior Scale-Revised questionnaire. Group differences in EEG measures were evaluated using ANCOVA, and multiple linear regressions were conducted to assess relationships between EEG and RRB measures. RESULTS: No group-level differences in infant EEG measures were observed. Marginal effects analysis of linear regressions revealed significant associations within the ASD group, such that higher periodic alpha power, lower peak alpha frequency, and lower aperiodic exponent, were associated with elevated RRBs at 24 months. No significant associations were observed for non-ASD outcome groups. LIMITATIONS: The sample size for ASD (N=19) was modest for examining brain-behavior relations. Larger sample sizes are needed to increase statistical power. CONCLUSION: For infants with later ASD diagnoses, measures of alpha and aperiodic activity measured at 1-year of age were associated with later manifestation of RRBs at 2-years. Longitudinal studies are needed to elucidate whether the early trajectory of these EEG measures and their dynamic relations in development influence manifestations of RRBs in ASD.

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8. Cirillo N. Considerations in Early Autism Diagnosis. JAMA Pediatr;2024 (Feb 5)

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9. Cui J, Zhai Z, Wang S, Song X, Qiu T, Yu L, Zhai Q, Zhang H. The role and impact of abnormal vitamin levels in autism spectrum disorders. Food Funct;2024 (Feb 5);15(3):1099-1115.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.

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10. Ethridge LE, Pedapati EV, Schmitt LM, Norris JE, Auger E, De Stefano LA, Sweeney JA, Erickson CA. Validating brain activity measures as reliable indicators of individual diagnostic group and genetically mediated sub-group membership Fragile X Syndrome. Res Sq;2024 (Jan 18)

Recent failures translating preclinical behavioral treatment effects to positive clinical trial results in humans with Fragile X Syndrome (FXS) support refocusing attention on biological pathways and associated measures, such as electroencephalography (EEG), with strong translational potential and small molecule target engagement. This study utilized guided machine learning to test promising translational EEG measures (resting power and auditory chirp oscillatory variables) in a large heterogeneous sample of individuals with FXS to identify best performing EEG variables for reliably separating individuals with FXS, and genetically-mediated subgroups within FXS, from typically developing controls. Best performing variables included resting relative frontal theta power, all combined whole-head resting power bands, posterior peak alpha frequency (PAF), combined PAF across all measured regions, combined theta, alpha, and gamma power during the chirp, and all combined chirp oscillatory variables. Sub-group analyses best discriminated non-mosaic FXS males via whole-head resting relative power (AUC = .9250), even with data reduced to a 20-channel clinical montage. FXS females were nearly perfectly discriminated by combined theta, alpha, and gamma power during the chirp (AUC = .9522). Results support use of resting and auditory oscillatory tasks to reliably identify neural deficit in FXS, and to identify specific translational targets for genetically-mediated sub-groups, supporting potential points for stratification.

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11. Faultersack J, Johnstad C, Zhang X, Greco M, Hokanson J. Follow-up of Secundum ASD, Muscular VSD, or PDA Diagnosed During Newborn Hospitalization. Res Sq;2024 (Jan 18)

BACKGROUND: The ideal follow-up of neonates who have a secundum atrial septal defect (ASD), muscular ventricular septal defect (VSD) or patent ductus arteriosus (PDA) remains uncertain. METHODS: Newborns with findings limited to a secundum ASD, muscular VSD and/or PDA on their last birth hospital echocardiogram and at least one outpatient follow-up echocardiogram performed between 9-1-17 and 9-1-21 were evaluated and patient follow-up assessed through 9-1-23. RESULTS: 95 babies met inclusion criteria. 43 babies had a secundum ASD, 41 had a muscular VSD and 54 had a PDA at newborn hospital discharge. 39/95 had more than one intracardiac shunt. 56 were discharged from care, 26 were still in follow-up and 13 were lost to recommended follow-up.No patients required intervention during the follow-up period of 2 to 6 years. Of those 43 with a secundum ASD 16 (37.2%) had demonstrated closure of the ASD and 13 (30.2%) were discharged from care with and ASD < 3.5 mm in diameter. 3/43 infants with secundum ASD had a defect large enough to easily warrant further follow-up. CONCLUSION: Even in this group who had early clinical follow-up recommended by a pediatric cardiologist, no baby discharged from their birth hospitalization with a secundum ASD, muscular VSD or PDA needed any intervention from 2 to 6 years of follow-up. Ongoing follow-up with echocardiography of those infants with a secundum ASD is of greater value than of those with muscular VSD or PDA.

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12. Grönniger B, Kimpe K, Singh A, Sadowski G. Simultaneous Water Sorption and Crystallization in ASDs 1: Stability Studies Lasting for Two Years. Mol Pharm;2024 (Feb 5);21(2):957-969.

One way to increase the slow dissolution rate and the associated low bioavailability of newly developed active pharmaceutical ingredients (APIs) is to dissolve the API in a polymer, leading to a so-called amorphous solid dispersion (ASD). However, APIs are often supersaturated in ASDs and thus tend to crystallize during storage. The kinetics of the crystallization process is determined by the amount of water the ASD absorbs during storage at relative humidity (RH), storage temperature, polymer type, and the drug load of the ASD. Here, the crystallization kinetics and shelf life of spray-dried ASDs were investigated for ASDs consisting of nifedipine (NIF) or celecoxib (CCX) as the APIs and of poly(vinylpyrrolidone-co-vinyl acetate) or hydroxypropyl methylcellulose acetate succinate as polymers. Samples were stored over 2 years at different RHs covering conditions above and below the glass transition of the wet ASDs. Crystallization kinetics and onset time of the crystallization were qualitatively studied by using powder X-ray diffraction and microscopic inspection and were quantitatively determined by using differential scanning calorimetry. It was found that the NIF ASDs crystallize much faster than CCX ASDs at the same drug load and at the same storage conditions due to both higher supersaturation and higher molecular mobility in the NIF ASDs. Experimental data on crystallization kinetics were correlated using the Johnson-Mehl-Avrami-Kolmogorov equation. A detailed thermodynamic and kinetic modeling will be performed in Part 2 of this paper series.

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13. Gupta N, Gupta M. Considerations in Early Autism Diagnosis. JAMA Pediatr;2024 (Feb 5)

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14. Hansford RL, Ouellette-Kuntz H, Griffiths R, Hallet J, Decker K, Dawe DE, Kristjanson M, Cobigo V, Shooshtari S, Stirling M, Kelly C, Brownell M, Turner D, Mahar A. Breast (female), colorectal, and lung cancer survival in people with intellectual or developmental disabilities: A population-based retrospective cohort study. Can J Public Health;2024 (Feb 5)

OBJECTIVES: Cancer is a leading cause of death among people living with intellectual or developmental disabilities (IDD). There is little empirical evidence documenting survival or comparing outcomes to those without IDD. This study investigated the association between IDD and cancer survival among adults with breast (female), colorectal, or lung cancer. METHODS: A population-based retrospective cohort study was conducted in Ontario, Canada, with routinely collected data. Patients with breast, colorectal, or lung cancer were included (2007‒2019). IDD status before cancer was determined using an established administrative data algorithm. The outcomes of interest included death from any cause and death from cancer. Cox proportional hazards models and competing events analyses using multivariable cause-specific hazards regression were completed. Analyses were stratified by cancer type. Interactions with age, sex, and stage at diagnosis, as well as sensitivity analyses, were completed. RESULTS: The final cohorts included 123,695 breast, 98,809 colorectal, and 116,232 lung cancer patients. Individuals with IDD experienced significantly worse survival than those without IDD. The adjusted hazard ratios of all-cause death were 2.74 (95% CI 2.41‒3.12), 2.42 (95% CI 2.18‒2.68), and 1.49 (95% CI 1.34‒1.66) times higher for breast, colorectal, and lung cancer patients with IDD relative to those without. These findings were consistent for cancer-specific deaths. With few exceptions, worse survival for people with IDD persisted regardless of stage at diagnosis. CONCLUSION: People with IDD experienced worse cancer survival than those without IDD. Identifying and intervening on the factors and structures responsible for survival disparities is imperative.

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15. Harstad E, Barbaresi W. Considerations in Early Autism Diagnosis-Reply. JAMA Pediatr;2024 (Feb 5)

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16. Karsh N, Hartston M, Hadad BS. Atypical Impact of Action Effect Delay on Motor Performance in Autism. J Autism Dev Disord;2024 (Feb 5)

Atypical sensory perception and motor impairments are primary features of autism spectrum disorder (ASD) that indicate atypical development and predict social and non-social challenges. However, their link is poorly understood. Sensory perception is often integrated with motor processes when a sensory effect is temporally contiguous with the motor response. Such sensory-motor coupling further improves motor behavior. Previous studies indicate alterations in sensory perception of action-effect temporal contiguity in ASD, which bares the question of how it may impact motor performance. People diagnosed with ASD and typically developed (TD) participants performed a speeded reaction-time task previously established to capture the facilitating impact of action’s perceptual effect on motor response selection. The sensitivity of this mechanism to delays in the effect was measured, manipulating the action-effect temporal contiguity in a within-subject design. An immediate action effect (compared to a No-effect condition) facilitated response selection in the TD group. This facilitation effect was evident in the ASD group but did not show the typical sensitivity to the effect delay. While in the TD group, RT was shorter in the short (225ms) compared to the long (675ms) action effect delay condition, this distinguished pattern was absent in the ASD group. The findings provide supporting evidence that atypical motor performance in ASD results, at least in part, from an altered sensory perception of action effect temporal contiguity. We discuss the results in light of the reduced perceptual specialization account in ASD and its potential for undermining adaptive sensorimotor processes.

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17. Li B, Heyne D, Scheeren A, Blijd-Hoogewys E, Rieffe C. School participation of autistic youths: The influence of youth, family and school factors. Autism;2024 (Feb 4):13623613231225490.

School-aged youths have a basic human right to participate in educational and recreational activities at school. Yet, autistic youths are at high risk of being excluded from school and from school-based activities. It is important to understand how this occurs, to ensure that all autistic youths have opportunities to participate in school activities that are equal to the opportunities of their non-autistic peers. The present study investigated multiple influences on the school participation of autistic youths, including youth factors (age and autistic traits), family factors (parent education level and parental self-efficacy for supporting their child’s schoolwork) and school factors (the impact of problems autistic youths experienced with the physical and social environments of school). Using an online survey, we gathered the views and experiences of the parents of 200 autistic youths aged between 4 and 16 years, in the Netherlands. We found that among the factors, only the impact of problems that autistic youths experienced with the physical environment of school was associated with their school participation. In particular, autistic youths who experienced greater difficulties with the physical environment of school had lower levels of school participation. Our findings highlight the pressing need to modify school environments to better accommodate the needs of autistic youths so that they can participate easily and comfortably.

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18. Northrup JB, Mazefsky CA, Day TN. Valence and Intensity of Emotional Expression in Autistic and Non-Autistic Toddlers. J Autism Dev Disord;2024 (Feb 3)

PURPOSE: Differences in emotional experience and expression have long been recognized as common in the presentation of autism, yet research examining emotional expression in early childhood is limited, with mixed findings. Understanding emotional reactivity and expression in autism in early life is an essential step towards uncovering the mechanisms of these risks and identifying targets for intervention. METHODS: The present study examined emotional expression in autistic (N = 17) and non-autistic (N = 20) toddlers (mean age = 25.27; SD = 1.88) during emotion elicitation tasks aimed at eliciting joy, frustration, and unease. Video recorded tasks were coded in ten second intervals for emotional valence and intensity, and the following variables were computed: proportion of time in positive, neutral, and negative affect; maximum intensity of positive and negative affect; and range of affect (i.e., most negative to most positive intensity). RESULTS: Autistic toddlers spent more time in neutral facial expressions, less time displaying positive affect, and had somewhat less intense positive emotional expression than non-autistic peers. Small differences were apparent in intensity of negative affect expression, while no differences emerged in duration of time spent in negative affect. CONCLUSION: Findings emphasize that differences may be more apparent in duration, rather than intensity of emotional expression, and that it may be particularly important to examine periods of « neutral » affect in young autistic children. Future research should consider the best ways to understand emotional reactivity in this population considering their unique interests, challenges, and communication styles.

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19. Park HR, Azzara D, Cohen ED, Boomhower SR, Diwadkar AR, Himes BE, O’Reilly MA, Lu Q. Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells. J Hazard Mater;2024 (Feb 5);463:132906.

Lead (Pb) and arsenic (As) are prevalent metal contaminants in the environment. Exposures to these metals are associated with impaired neuronal functions and adverse effects on neurodevelopment in children. However, the molecular mechanisms by which Pb and As impair neuronal functions remain poorly understood. Here, we identified F2RL2, TRIM16L, and PANX2 as novel targets of Nuclear factor erythroid 2-related factor 2 (NRF2)-the master transcriptional factor for the oxidative stress response-that are commonly upregulated with both Pb and As in human neural progenitor cells (NPCs). Using a ChIP (Chromatin immunoprecipitation)-qPCR assay, we showed that NRF2 directly binds to the promoter region of F2RL2, TRIM16L, and PANX2 to regulate expression of these genes. We demonstrated that F2RL2, PANX2, and TRIM16L have differential effects on cell death, proliferation, and differentiation of NPCs in both the presence and absence of metal exposures, highlighting their roles in regulating NPC function. Furthermore, the analyses of the transcriptomic data on NPCs derived from autism spectrum disorder (ASD) patients revealed that dysregulation of F2RL2, TRIM16L, and PANX2 was associated with ASD genetic backgrounds and ASD risk genes. Our findings revealed that Pb and As induce a shared NRF2-dependent transcriptional response in NPCs and identified novel genes regulating NPC function. While further in vivo studies are warranted, this study provides a novel mechanism linking metal exposures to NPC function and identifies potential genes of interest in the context of neurodevelopment.

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20. Safra DC, Chayen G, Jacob R. Children with autism spectrum disorder did not have more complications as a result of serious acute conditions than the overall population. Acta Paediatr;2024 (Feb 5)

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21. Shi A, Liu D, Wu H, Zhu R, Deng Y, Yao L, Xiao Y, Lorimer GH, Ghiladi RA, Xu X, Zhang R, Xu H, Wang J. Serum binding folate receptor autoantibodies lower in autistic boys and positively-correlated with folate. Biomed Pharmacother;2024 (Feb 5);172:116191.

Folate receptor autoantibody (FRAA) has caught increasing attention since its discovery in biological fluids of patients with autism spectrum disorder (ASD), but quantification and understanding of its function are still in their infancy. In this study, we aimed to quantify serum binding-FRAA and explore its relation with serum folate, vitamin B(12) (VB(12)) and ferritin. We quantitated serum binding-FRAA in 132 ASD children and 132 typically-developing (TD) children, as well as serum levels of folate, VB(12) and ferritin. The results showed that serum binding-FRAA in the ASD group was significantly lower than that in the TD group (p < 0.0001). Further analysis showed that the difference between these two groups was attributed to boys in each group, not girls. There was no statistically significant difference in folate levels between the ASD and TD groups (p > 0.05). However, there was significant difference in boys between these two groups, not girls. Additionally, the combination of nitrite and binding-FRAA showed potential diagnostic value in patients with ASD (AUC > 0.7). Moreover, in the ASD group, the level of folate was consistent with that of binding-FRAA, whereas in the TD group, the binding-FRAA level was high when the folate level was low. Altogether, these differences revealed that the low serum FRAA in autistic children was mediated by multiple factors, which deserves more comprehensive investigation with larger population and mechanistic studies.

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22. Tian Y, Yu F, Yun E, Lin JW, Man HY. mRNA nuclear retention reduces AMPAR expression and promotes autistic behavior in UBE3A-overexpressing mice. EMBO Rep;2024 (Feb 5)

UBE3A is a common genetic factor in ASD etiology, and transgenic mice overexpressing UBE3A exhibit typical autistic-like behaviors. Because AMPA receptors (AMPARs) mediate most of the excitatory synaptic transmission in the brain, and synaptic dysregulation is considered one of the primary cellular mechanisms in ASD pathology, we investigate here the involvement of AMPARs in UBE3A-dependent ASD. We show that expression of the AMPAR GluA1 subunit is decreased in UBE3A-overexpressing mice, and that AMPAR-mediated neuronal activity is reduced. GluA1 mRNA is trapped in the nucleus of UBE3A-overexpressing neurons, suppressing GluA1 protein synthesis. Also, SARNP, an mRNA nuclear export protein, is downregulated in UBE3A-overexpressing neurons, causing GluA1 mRNA nuclear retention. Restoring SARNP levels not only rescues GluA1 mRNA localization and protein expression, but also normalizes neuronal activity and autistic behaviors in mice overexpressing UBE3A. These findings indicate that SARNP plays a crucial role in the cellular and behavioral phenotypes of UBE3A-induced ASD by regulating nuclear mRNA trafficking and protein translation of a key AMPAR subunit.

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23. Ul Mudassir B, Agha Z. Novel and known minor alleles of CNTNAP2 gene variants are associated with comorbidity of intellectual disability and epilepsy phenotypes: a case-control association study reveals potential biomarkers. Mol Biol Rep;2024 (Feb 5);51(1):276.

BACKGROUND: Neurodevelopmental disorders are heterogeneous due to underlying multiple shared genetic pathways and risk factors. Intellectual disability, epilepsy and autism spectrum disorder phenotypes overlap which indicates the diverse effects of common genes. Recent studies suggested the probable contribution of CNTNAP2 gene polymorphisms to the comorbidity of these neurological conditions. METHODS AND RESULTS: This study was conducted to investigate the role of CNTNAP2 polymorphisms rs147815978 (G>T) and rs2710102 (A>G) as a risk factor for comorbidity of intellectual disability and epilepsy in a group of 345 individuals including 170 patients and 175 healthy controls recruited from various ethnic groups of Pakistani population. Our case-control study group was genotyped by tetra primer ARMS-PCR technique and results were analysed to know the effects of CNTNAP2 rs147815978 (G>T) and rs2710102 (A>G) polymorphisms in the group. The frequency of risk allele T (rs147815978) and risk allele G (rs2710102) for homozygous recessive genotypes (TT/GG) in our study group was 36.47% while odds ratios for risk allele T (rs147815978) was 5.45 (3.90-7.61: 95% CI, P = 0.000) and that for risk allele G (rs2710102) was 2.39 (1.76-3.24: 95% CI, P = 0.0001). Homozygous recessive genotypes (TT/GG) appeared only in cases and not in control group which indicated these as suspected risk genotypes and the significant association (p < 0.05%) of CNTNAP2 gene polymorphisms rs147815978 (G>T) and rs2710102 (A>G) with co-occurrence of intellectual disability and epilepsy phenotypes in our study group which is in HWE (χ(2) = 174, P < 0.0001). Logistic regression analysis shows additive (p < 0.0001) and multiplicative (p < 0.001) models which confirms significant association of both the polymorphisms in our data, which are closely located on same haplotype (D' = - 0.168). CONCLUSIONS: We propose that CNTNAP2 rs147815978 (G>T) and rs2710102 (A>G) polymorphisms are possible risk loci for overlapping neurodevelopmental disorders in Pakistani population. We propose the role of a previously reported common SNP rs2710102 (A>G) with a rarely reported novel SNP rs147815978 (G>T) for CNTNAP2 gene association with neurodevelopmental disorders in our data. Our study has expanded the knowledge of CNTNAP2 gene polymorphisms as probable biomarkers for susceptibility of co-occurrence of intellectual disability and epilepsy phenotypes in Pakistani population. We hope that our study will open new horizons of CNTNAP2 gene variants research to cure the neurological conditions in Pakistani population where consanguinity is a tradition and prevalence of neurodevelopmental disorders has increased from 1 to 2% during last 5 years.

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24. Vu H, Bowden N, Gibb S, Audas R, Dacombe J, McLay L, Sporle A, Stace H, Taylor B, Thabrew H, Theodore R, Tupou J, Schluter PJ. Mortality risk among Autistic children and young people: A nationwide birth cohort study. Autism;2024 (Feb 4):13623613231224015.

Existing literature indicates that Autistic people have shorter life expectancy, but little is known about the mortality risk among Autistic children and young people (0-24 years). We used a 15-year nationwide birth cohort study to estimate the mortality risk among Autistic children and young people in Aotearoa/New Zealand. The study included 895,707 children and 11,919 (1.4%) were Autistic. We found that autism was associated with a significantly higher mortality risk compared to the non-Autistic population. In addition, we found that this risk was significantly higher among females compared to males and for those with a co-occurring intellectual disability. Increased efforts are required to better meet the health needs of this population.

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25. Wang A, Little ID, Carter D, Pham S, Piper M, Ramírez-Renta GM, Telaak S, Gunter C. Provider-reported experiences, barriers, and perspectives on genetic testing as part of autism diagnosis. PLoS One;2024;19(2):e0296942.

Several professional organizations recommend conducting genetic testing as part of the autism diagnosis process, as it can provide additional information and benefits for autistic people and their families. However, there is disagreement among autism communities about whether genetic testing reflects autistic people’s best interests. In practice, rates of clinical genetic testing for autism are much lower than diagnoses, creating a large gap between clinical guidelines and real clinical encounters. To investigate one potential source of this gap, we interviewed 14 healthcare providers about the autism diagnostic process and their actions related to autism genetic testing. We recruited a sample of primarily Ph.D. level-psychologists and analyzed our qualitative data using a five-step framework analysis method. Participants generally had positive or mixed views of genetic testing in autism. They described their current experiences of implementation of genetic testing, including that they did not often find it changed their clinical practice. Only some providers recommended it to everyone receiving an autism diagnosis. They also listed factors which discourage families from getting testing, including high costs, families feeling overwhelmed, other support needs taking priority, and ethical implications. Notably, providers highlighted a trend of referring patients to research genetic testing rather than clinical testing, which may provide a cheaper and easier alternative but is not likely to return results to participants. Finally, participants felt they needed more training in genetics and listed specific topics of uncertainty. Our research highlights a need to further educate clinicians in the uses and limitations of genetic testing for autism and suggests content areas of focus for genetics educators.

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26. Yan L, Tian L, Zhang Y, Liu Y, Cao J, Li D, Zou J, Li H. [Analysis of clinical features and genetic variant in a child with Cowden syndrome 1]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi;2024 (Feb 10);41(2):230-233.

OBJECTIVE: To explore the genetic etiology of a child with Cowden syndrome 1 (CS1). METHODS: A child who had visited the Ningbo Women and Children’s Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c.781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

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27. Zhou W, Yang M, Tang J, Wang J, Hu B. Gaze Patterns in Children with Autism Spectrum Disorder to Emotional Faces: Scanpath and Similarity. IEEE Trans Neural Syst Rehabil Eng;2024 (Feb 5);Pp

Autism spectrum disorder (ASD) one of the fastest-growing diseases in the world is a group of neurodevelopmental disorders. Eye movement as a biomarker and clinical manifestation represents unconscious brain processes that can objectively disclose abnormal eye fixation of ASD. With the aid of eye-tracking technology, plentiful methods that identify ASD based on eye movements have been developed, but there are rarely works specifically for scanpaths. Scanpaths as visual representations describe eye movement dynamics on stimuli. In this paper, we propose a scanpath-based ASD detection method, which aims to learn the atypical visual pattern of ASD through continuous dynamic changes in gaze distribution. We extract four sequence features from scanpaths that represent changes and the differences in feature space and gaze behavior patterns between ASD and typical development (TD) are explored based on two similarity measures, multimatch and dynamic time warping (DTW). It indicates that ASD children show more individual specificity, while normal children tend to develop similar visual patterns. The most noticeable contrasts lie in the duration of attention and the spatial distribution of visual attention along the vertical direction. Classification is performed using Long Short-Term Memory (LSTM) network with different structures and variants. The experimental results show that LSTM network outperforms traditional machine learning methods.

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