1. Baylisascaris procyonis Roundworm Infection in Child with Autism Spectrum Disorder, Washington, USA, 2022. The Pediatric infectious disease journal. 2023.

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2. Albaum CS, Sellitto T, Vashi N, Bohr Y, Weiss JA. Treatment Engagement as a Predictor of Therapy Outcome Following Cognitive Behaviour Therapy for Autistic Children. Journal of autism and developmental disorders. 2023.

PURPOSE: Active engagement in one’s therapy is a key contributor to successful outcomes. Research on child engagement in cognitive behaviour therapy (CBT) has largely focused on youth without autism. This longitudinal study examined multiple indicators of child engagement in relation to outcomes for autistic children who took part in CBT for emotion regulation. METHOD: Data were collected from 60 autistic children who were between 8 and 13 years of age (86.7% male; M(age) = 9.58 years, SD = 1.44 years; 75% White). Indicators of child engagement included independent observer ratings of in-session involvement, as measured by the Child Involvement Rating Scale, and therapist ratings of the therapeutic relationship and homework completion using single-item measures. Indicators of engagement were measured at early (i.e., first third), middle (i.e., mid third), and late (i.e., final third) stages of treatment. Parent-reported emotion regulation was the primary treatment outcome, as measured by the Emotion Regulation Checklist. RESULTS: After controlling for pre-treatment scores, in-session involvement significantly predicted some aspects of post-treatment emotion regulation, whereas therapeutic relationship and homework completion did not. CONCLUSIONS: Child in-session involvement throughout therapy may be particularly relevant for treatment change. Addressing issues related to in-session involvement early in treatment may help to promote therapeutic success for autistic children.

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3. Arnardóttir Á, Guðmundsdóttir L, Hannesdóttir DK, Halldórsson F, Auðardóttir H, Sveinbjörnsdóttir B. A Pilot Study on the FEST program – Friendship and Emotional Skills Training for Children on the Autism Spectrum. Journal of autism and developmental disorders. 2023.

PURPOSE: Social skills difficulties among children on the autism spectrum can impede social, emotional, and academic development, especially with increasing age and social demands. This pilot study examined the efficacy of a 5-week skill-building program for children on the autism spectrum. Although effective social skills programs are available for adolescents with autism spectrum disorder (ASD), very few programs are explicitly intended for 10-12-year-old children. METHODS: This pilot study examined the efficacy of the 9-session Friendship and Emotional Skills Training (FEST Program) for children with ASD without intellectual disability. Participants were 22 children randomly assigned to the FEST Program or a delayed intervention control group. Eleven children (boys = 8; girls = 3) received the FEST Program in two separate groups, and 11 were wait-listed for a delayed intervention. Parents, teachers, and the children answered questionnaires at baseline, post-intervention, and a 3-month follow-up. RESULTS: Upon completing the FEST Program (post-intervention), parents reported an increase in overall social skills (on the Social Skills Rating System – SSRS) and a reduction on the Autistic Mannerisms factor (on the Social Responsiveness Scale – SRS) compared to the control group. These changes were also maintained at the 3-month follow-up. The children’s assessment also showed a significant increase in assertion (on the SSRS) post-intervention. Teachers also reported a significant reduction on the Autistic Mannerisms factor at the 3-month follow-up. CONCLUSION: The findings suggest that the FEST Program shows some promising results as one possibility for supporting children with ASD and their families in everyday life.

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4. Benitah KC, Kavaliers M, Ossenkopp KP. The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle. Pharmacology, biochemistry, and behavior. 2023; 231: 173630.

Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety.

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5. Bey AL, Sabatos-DeVito M, Carpenter KLH, Franz L, Howard J, Vermeer S, Simmons R, Troy JD, Dawson G. Automated Video Tracking of Autistic Children’s Movement During Caregiver-Child Interaction: An Exploratory Study. Journal of autism and developmental disorders. 2023.

Objective, quantitative measures of caregiver-child interaction during play are needed to complement caregiver or examiner ratings for clinical assessment and tracking intervention responses. In this exploratory study, we examined the feasibility of using automated video tracking, Noldus EthoVision XT, to measure 159 2-to-7-year-old autistic children’s patterns of movement during play-based, caregiver-child interactions and examined their associations with standard clinical measures and human observational coding of caregiver-child joint engagement. Results revealed that autistic children who exhibited higher durations and velocity of movement were, on average, younger, had lower cognitive abilities, greater autism-related features, spent less time attending to the caregiver, and showed lower levels of joint engagement. After adjusting for age and nonverbal cognitive abilities, we found that children who remained in close proximity to their caregiver were more likely to engage in joint engagement that required support from the caregiver. These findings suggest that video tracking offers promise as a scalable, quantitative, and relevant measure of autism-related behaviors.

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6. Bozkus-Genc G, Yucesoy-Ozkan S. Efficacy of a Parent-Implemented Pivotal Response Treatment for Children with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2023.

PURPOSE: Pivotal response treatment (PRT) is a well-established intervention addressing core symptoms of autism spectrum disorder (ASD), with parent involvement as a key component. The current study aimed to examine the effects of PRT parent training on parent fidelity and provide descriptive analyses of parent-child interactions before and after parent training. It also probed parental acceptance and satisfaction with the program. METHODS: A concurrent multiple baseline design across participants was used to evaluate the effectiveness of the parent training program. Four parents (range 32-47 years old) and their children with ASD participated in the study. The intervention comprised 12 one-on-one parent training sessions over six consecutive weeks. The visual analysis and effect size calculation (Tau-U) were used to evaluate functional relationship between independent and dependent variables. The descriptive analysis was used to analyze parent-child interaction data. RESULTS: The findings reveal that all parents learned and maintained PRT with a high level of fidelity, they also enhanced awareness to create more opportunities for interactions during free play, and the parents were very satisfied with the program. The results also indicate that the six-week parent training program is effective in teaching parents to implement PRT with their children. CONCLUSION: These results suggest that the parent training program may be a promising treatment model that is effective, efficient, and cost-effective. Implications for future research and practice are then discussed.

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7. Choi H, Kim JH, Kim H, Cheon KA. Identifying major predictors for parenting stress in a caregiver of autism spectrum disorder using machine learning models. Frontiers in neuroscience. 2023; 17: 1229155.

INTRODUCTION: Previous studies have investigated predictive factors for parenting stress in caregivers of autism spectrum disorder (ASD) patients using traditional statistical approaches, but their study settings and results were inconsistent. Herein, this study aimed to identify major predictors for parenting stress in this population by developing explainable machine learning models. METHODS: Study participants were collected from the Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, the Republic of Korea between March 2016 and October 2020. A total of 36 model features were used, which include subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) for caregivers’ psychopathology, Social Responsiveness Scale-2 for core symptoms, and Child Behavior Checklist (CBCL) for behavioral problems. Machine learning classifiers [eXtreme Gradient Boosting (XGBoost), random forest (RF), logistic regression, and support vector machine (SVM) classifier] were generated to predict severe total parenting stress and its subscales (parental distress, parent-child dysfunctional interaction, and difficult child). Model performance was assessed by area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. We utilized the SHapley Additive exPlanations tree explainer to investigate major predictors. RESULTS: A total of 496 participants were included [mean age of ASD patients 6.39 (SD 2.24); 413 men (83.3%)]. The best-performing models achieved an AUC of 0.831 (RF model; 95% CI 0.740-0.910) for parental distress, 0.814 (SVM model; 95% CI 0.720-0.896) for parent-child dysfunctional interaction, 0.813 (RF model; 95% CI 0.724-0.891) for difficult child, and 0.862 (RF model; 95% CI 0.783-0.930) for total parenting stress on the test set. For the total parenting stress, ASD patients’ aggressive behavior and anxious/depressed, and caregivers’ depression, social introversion, and psychasthenia were the top 5 leading predictors. CONCLUSION: By using explainable machine learning models (XGBoost and RF), we investigated major predictors for each subscale of the parenting stress index in caregivers of ASD patients. Identified predictors for parenting stress in this population might help alert clinicians whether a caregiver is at a high risk of experiencing severe parenting stress and if so, providing timely interventions, which could eventually improve the treatment outcome for ASD patients.

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8. Deng S, Feng X, Yang M, Yu W, Wu Z, Zhu X, Song Z, Cheng S. LAMP1 as a novel molecular biomarker to predict the prognosis of the children with autism spectrum disorder using bioinformatics approaches. Scientific reports. 2023; 13(1): 14040.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets.

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9. Evans MM, Kim J, Abel T, Nickl-Jockschat T, Stevens HE. Developmental disruptions of the dorsal striatum in autism spectrum disorder. Biological psychiatry. 2023.

Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental condition that is characterized by social and communication deficits as well as patterns of restricted, repetitive behavior. Abnormal brain development has long been postulated to underlie ASD, but longitudinal studies aimed at understanding the developmental course of the disorder have been limited. More recently, abnormal development of the striatum in ASD has become an area of interest in research, partially due to overlap of striatal functions and deficit areas in ASD, as well as the critical role of striatum in early development when ASD is first detected. Focusing on the dorsal striatum and the associated symptom domain of restricted, repetitive behavior, we review the current literature on dorsal striatal abnormalities in ASD, including studies on functional connectivity, morphometry, and cellular and molecular substrates. We highlight that observed striatal abnormalities in ASD are often dynamic across development, displaying disrupted developmental trajectories. Important findings include an abnormal trajectory of increasing cortico-striatal functional connectivity with age and increased striatal growth during childhood in ASD. We end by discussing striatal findings from animal models of ASD. In sum, the studies reviewed here demonstrate a key role for developmental disruptions of the dorsal striatum in the pathogenesis of ASD. Directing attention toward these findings will improve our understanding of ASD and of how associated deficits may be better addressed.

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10. Fowler SP, Gimeno Ruiz de Porras D, Swartz MD, Stigler Granados P, Heilbrun LP, Palmer RF. Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study. Nutrients. 2023; 15(17).

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DS(early)) or equivalent aspartame (ASP(early): ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DS(early) and ASP(early) were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DS(early) odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASP(early) odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DS(early) OR = 2.7 (95% CI: 0.9, 8.4); ASP(early) OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.

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11. Kimi S, Maiti R, Srinivasan A, Mishra BR, Hota D. Efficacy and safety of V(1a) receptor antagonists in autism spectrum disorder: A meta-analysis. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 2023.

This meta-analysis has evaluated the efficacy and safety of V(1a) receptor antagonists in ASD compared to placebo. The reviewers extracted data from four relevant clinical trials after a literature search on databases and clinical trial registries. Quality assessment was done using the risk of bias assessment tool, and the random-effects model was used to estimate effect size. Subgroup analysis, meta-regression and sensitivity analysis were done. PRISMA guidelines were followed in the selection, analysis and reporting of findings. V(1a) receptor antagonists did not reduce Vineland II Adaptive behaviour composite score significantly (SMD: 0.14; 95% CI: -0.06-0.35; p = 0.16; PI: -0.44-0.73), communication domain subscale score and socialization domain subscale score. The change in daily living skills domain subscale score was significant and favourable for V(1a) receptor antagonists (SMD: 0.15; 95% CI: 0.03-0.26; p = 0.01). The subgroup analysis revealed a significant improvement in Vineland II Adaptive behaviour composite score with doses <10 mg (SMD: 0.45; 95% CI: 0.11-0.78; p = 0.009). Meta-regression does not show a significant association between SMD of ASD symptom score reduction with the duration and dose of V(1a) receptor antagonist therapy. Treatment-emergent adverse effects were not serious and dose dependent. Low doses (<10 mg) of V(1a) receptor antagonist may be effective in reducing the core symptoms of ASD compared to placebo; however, future active-controlled clinical trials are necessary to generate conclusive evidence.

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12. Kong XJ, Kang J, Liu K. Probiotic and intra-nasal oxytocin combination therapy on autonomic function and gut-brain axis signaling in young children and teens with autism spectrum disorder. Journal of psychiatric research. 2023; 166: 1-9.

Autonomic dysfunction has been widely studied in individuals with autism spectral disorder (ASD); however, the autonomic response to probiotic and oxytocin (OT) combination intervention has not yet been explored. We conducted the present study that includes 35 individuals with ASD aged 3-20 years to explore autonomic responses to daily Lactobacillus plantarum probiotic supplementation and OT nasal spray treatment both alone and in combination. We identified significant improvements in autonomic indices from subjects receiving combination treatment relative to those receiving placebo. Parameters that were observed to improve following combination treatment are time domain metrics of heart rate variability (HRV), including the root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of normal-to-normal R-R intervals (SDNN), and proportion of the number of pairs of adjacent NN intervals that differ by more than 50ms (pNN50, p < 0.05). Furthermore, individuals that received either probiotics or OT alone demonstrated fewer changes in RMSSD, pNN50, and SDNN. Several parameters that demonstrated significant improvements in combination therapy were found to be correlated with baseline levels of OT (LF power: r = -0.86, p = 0.024; mean HR: r = 0.89, p = 0.012). Additionally, Social Responsiveness Scale (SRS) raw total scores (mean HR, r = 0.86, p = 0.024) and Aberrant Behavior Checklist (ABC) raw total scores (mean HR r = 0.94, p = 0.017) were correlated with mean heart rate (HR) and HRV-derived parameters. These results provide further evidence of synergy of probiotic and OT combination and help us gain a better understanding of the role of the gut-brain axis in ASD phenotypes and pathogenesis.

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13. Krupa M, Boominathan P, Sebastian S, Raman PV. Joint Engagement in Mother-Child Dyads of Autistic and Non-Autistic Children Among Asian Indian Tamil Speaking Families. Journal of autism and developmental disorders. 2023.

This study profiled various levels of engagement and related communication behaviours among 50 Asian Indian Tamil autistic children (AUT) and their mothers. The interaction was compared with two groups of mother-child dyads of non-autistic (NA) children, 50 in each group, matched for chronological age (CA), and for language level (LL). Results indicated that despite mother’s efforts to engage with their children, autistic children were often ‘engaged with objects’ or remained ‘unengaged’ due to children’s preference for solitary play, while NA children were often engaged in ‘co-ordinated’ and ‘people engagement’. Across the three groups, mothers predominantly took the lead and dominated the interaction, irrespective of children’s language levels. These initiations by the mothers were often to provide instructions and to ask ‘What’ questions. Autistic children initiated communication predominantly to ask for an object and responded often in the form of negations and protests with limited verbal output or non-verbally. Most of the communication behaviours of both children and mothers in AUT group was quantitatively and qualitatively different when compared to those in both the NA groups, indicating unique nature of interactions despite matching for CA or LL. The observations from the study highlights the need for considering adult’s contingent behaviours also, while assessing communication skills of autistic children in order to provide effective intervention.

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14. Longo F, Aryal S, Anastasiades PG, Maltese M, Baimel C, Albanese F, Tabor J, Zhu JD, Oliveira MM, Gastaldo D, Bagni C, Santini E, Tritsch NX, Carter AG, Klann E. Cell-type-specific disruption of cortico-striatal circuitry drives repetitive patterns of behavior in fragile X syndrome model mice. Cell reports. 2023; 42(8): 112901.

Individuals with fragile X syndrome (FXS) are frequently diagnosed with autism spectrum disorder (ASD), including increased risk for restricted and repetitive behaviors (RRBs). Consistent with observations in humans, FXS model mice display distinct RRBs and hyperactivity that are consistent with dysfunctional cortico-striatal circuits, an area relatively unexplored in FXS. Using a multidisciplinary approach, we dissect the contribution of two populations of striatal medium spiny neurons (SPNs) in the expression of RRBs in FXS model mice. Here, we report that dysregulated protein synthesis at cortico-striatal synapses is a molecular culprit of the synaptic and ASD-associated motor phenotypes displayed by FXS model mice. Cell-type-specific translational profiling of the FXS mouse striatum reveals differentially translated mRNAs, providing critical information concerning potential therapeutic targets. Our findings uncover a cell-type-specific impact of the loss of fragile X messenger ribonucleoprotein (FMRP) on translation and the sequence of neuronal events in the striatum that drive RRBs in FXS.

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15. Ma Y, Wang Q, Cao L, Li L, Zhang C, Qiao L, Liu M. Multi-Scale Dynamic Graph Learning for Brain Disorder Detection With Functional MRI. IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society. 2023; 31: 3501-12.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used in the detection of brain disorders such as autism spectrum disorder based on various machine/deep learning techniques. Learning-based methods typically rely on functional connectivity networks (FCNs) derived from blood-oxygen-level-dependent time series of rs-fMRI data to capture interactions between brain regions-of-interest (ROIs). Graph neural networks have been recently used to extract fMRI features from graph-structured FCNs, but cannot effectively characterize spatiotemporal dynamics of FCNs, e.g., the functional connectivity of brain ROIs is dynamically changing in a short period of time. Also, many studies usually focus on single-scale topology of FCN, thereby ignoring the potential complementary topological information of FCN at different spatial resolutions. To this end, in this paper, we propose a multi-scale dynamic graph learning (MDGL) framework to capture multi-scale spatiotemporal dynamic representations of rs-fMRI data for automated brain disorder diagnosis. The MDGL framework consists of three major components: 1) multi-scale dynamic FCN construction using multiple brain atlases to model multi-scale topological information, 2) multi-scale dynamic graph representation learning to capture spatiotemporal information conveyed in fMRI data, and 3) multi-scale feature fusion and classification. Experimental results on two datasets show that MDGL outperforms several state-of-the-art methods.

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16. MacDonald DN, Bedford SA, Olafson E, Park MTM, Devenyi GA, Tullo S, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Shinohara RT, Spencer MD, Suckling J, Taylor MJ, Thurm A, Lai MC, Chakravarty MM. Characterizing Subcortical Structural Heterogeneity in Autism. bioRxiv : the preprint server for biology. 2023.

Autism presents with significant phenotypic and neuroanatomical heterogeneity, and neuroimaging studies of the thalamus, globus pallidus and striatum in autism have produced inconsistent and contradictory results. These structures are critical mediators of functions known to be atypical in autism, including sensory gating and motor function. We examined both volumetric and fine-grained localized shape differences in autism using a large ( n =3145, 1045-1318 after strict quality control), cross-sectional dataset of T1-weighted structural MRI scans from 32 sites, including both males and females (assigned-at-birth). We investigated three potentially important sources of neuroanatomical heterogeneity: sex, age, and intelligence quotient (IQ), using a meta-analytic technique after strict quality control to minimize non-biological sources of variation. We observed no volumetric differences in the thalamus, globus pallidus, or striatum in autism. Rather, we identified a variety of localized shape differences in all three structures. Including age, but not sex or IQ, in the statistical model improved the fit for both the pallidum and striatum, but not for the thalamus. Age-centered shape analysis indicated a variety of age-dependent regional differences. Overall, our findings help confirm that the neurodevelopment of the striatum, globus pallidus and thalamus are atypical in autism, in a subtle location-dependent manner that is not reflected in overall structure volumes, and that is highly non-uniform across the lifespan.

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17. Magen E, Geishin A, Merzon E, Green I, Golan-Cohen A, Vinker S, Israel A. Prevalence of neurological diseases among patients with selective IgA deficiency. Allergy and asthma proceedings. 2023; 44(5): e17-e21.

Background: There are no published epidemiologic studies with regard to the prevalence of neurologic diseases among subjects with selective immunoglobulin A (IgA) deficiency (sIgAD). Objective: To investigate the prevalence of neurologic diseases among the Israeli population with sIgAD. Methods: A population-based case-control study among members of a large nationwide health maintenance organization in Israel providing services to > 700,000 members. The sIgAD group included individuals ≥4 years of age with a serum IgA level of <0.07 g/L and with a diagnosis of sIgAD. The control group was randomly sampled from the entire study population with a case-control ratio of five controls for each case (1:5), with exact matching for age, gender, ethnic group, and socioeconomic status category. Results: A total of 796 subjects ages 20.58 ± 15.46 years; 391 female subjects (49.1%) were identified as having sIgAD. The control group was constituted of 3980 matched subjects. The sIgAD group was characterized by a higher prevalence of autism spectrum disorder and tic disorders. Migraine was less prevalent in the sIgAD group (19 [2.39%]) than in the control group (168 [4.22%]), odds ratio (OR) 0.55 (95% confidence interval {CI}, 0.34-0.90); p = 0.016]. More cases of subjects with epilepsy were observed in the sIgAD group (14 [1.76%]) than in the control group (31 [0.80%]), OR 2.28 (95% CI, 1.12 - 4.44; p = 0.015). Conclusion: Our observation raises the question of the role of IgA in noninfectious diseases of the central nervous system. Further basic studies are needed to explain our observation.

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18. Mournet AM, Bal VH, Kleiman EM. Concordance Between the Ask Suicide Screening Questions (ASQ) and Self-Injurious Thoughts and Behaviors Interview-Self Report (SITBI-SR) Among Autistic and Non-Autistic Adults. Archives of suicide research : official journal of the International Academy for Suicide Research. 2023: 1-12.

OBJECTIVE: This study sought to examine concordance between two commonly used measures of suicidal thoughts and behaviors: the Ask Suicide-Screening Questions (ASQ) and the Self-Injurious Thoughts and Behaviors Interview-Self Report (SITBI-SR). Agreement was operationalized as the presence past month suicidal ideation and lifetime suicide attempts. To explore the utilization of these tools among neurodiverse samples, we also examined the concordance across autistic and non-autistic adults. METHODS: The sample consisted of 200 individuals recruited online. Half of the sample self-reported a diagnosis of autism. A series of Cohen’s kappas and confidence intervals were computed to assess agreement between the ASQ and SITBI-SR. Cohen’s kappa was computed separately for each set of comparisons for the autistic and non-autistic samples. RESULTS: Past month suicidal ideation had a kappa of 0.61 (95%CI = 0.48-0.73). The kappa for lifetime suicide attempts was 0.86 (95%CI = 0.78-0.94). There were no significant differences in agreement between the two measures for autistic versus non-autistic individuals. CONCLUSIONS: Current findings suggest that the ASQ and SITBI-SR have high concordance with one another. Given that the ASQ and the SITBI-SR are both validated in the general population and that concordance was high and not significantly different based on autism status, the current study provides preliminary evidence that the ASQ and the SITBI-SR function similarly for autistic individuals.HIGHLIGHTSPeople do not always respond consistently to different STB assessment methods.Findings suggest that the ASQ and SITBI-SR have high concordance with one another.Evidence provided that these measures function similarly for autistic individuals.

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19. Nah YH, Lee RS, Chen AS. Do Types of Information in an Animated Video Intervention Affect University Students’ Autism Knowledge and Openness Towards Peers on the Autism Spectrum?. Journal of autism and developmental disorders. 2023.

This pre-test post-test control group design sought to compare the effectiveness of delivering different types of information ([1] factual information vs. [2] factual information + descriptive and explanatory information vs. [3] factual information + descriptive, explanatory + directive information) in an animated video intervention in increasing university students’ autism knowledge and openness toward peers on the autism spectrum. The sample consisted of 92 undergraduates (27 males, 65 females; age range = 18-36) from various universities in Singapore. Participants were randomly assigned to one of the three experimental conditions/videos, where they completed a measure of their autism knowledge and openness scale, before viewing a 5-minute long animated video containing different types of information about autism. After which, participants completed the measure of autism knowledge and openness scale again, followed by a measure of their empathy level. Results indicated that participants’ autism knowledge improved following the viewing of the animated video. However, the three different videos containing different types of information did not differ in influencing participants’ openness toward peers on the autism spectrum. Nevertheless, qualitative responses proposed that the video containing factual information, with descriptive, explanatory, and directive information was useful in helping participants to know how to interact with their peers on the autism spectrum. The findings of this study provide preliminary support for the most effective method to educate and raise awareness about autism, among the general student population in order to foster a supportive and inclusive environment.

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20. Nelson MA, Shaffer RC, Schmitt LM, Coffman MC, Horn PS, Reisinger DL, Erickson CA. Health Related Quality of Life in Autistic Youth and Their Families. Journal of autism and developmental disorders. 2023.

PURPOSE: The construct Quality of Life (QoL) involves a range of factors related to one’s well-being. Individuals on the autism spectrum have been previously reported to have lower QoL. The purpose of the present study is to examine QoL in autistic individuals and their families and to evaluate associations between QoL and measures of functioning using the PedsQL 4.0. METHOD: Thirty-six autistic youth (ages 9-21 years) and their caregivers completed the PedsQL. Caregivers completed additional measures of their children’s adaptive, social, behavioral, and emotional functioning. RESULTS: Parents and youth generally agreed on the PedsQL, with the exception of the Social Functioning domain, which youth rated higher. The parent rated PedsQL did not correlate with most areas of caregiver-rated functioning; however, there were significant negative correlations between irritability and family functioning. CONCLUSION: Limitations of this study included small sample size; broad range of intellectual functioning; lack of sample diversity; and likely recruiting bias for a drug treatment study. Despite limitations, HRQoL is an important feature that should be measured in addition to features of autism or symptoms of co-occurring symptoms.

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21. Ong JH, Zhao C, Bacon A, Leung FYN, Veic A, Wang L, Jiang C, Liu F. The Relationship Between Autism and Pitch Perception is Modulated by Cognitive Abilities. Journal of autism and developmental disorders. 2023.

Previous studies reported mixed findings on autistic individuals’ pitch perception relative to neurotypical (NT) individuals. We investigated whether this may be partly due to individual differences in cognitive abilities by comparing their performance on various pitch perception tasks on a large sample (n = 164) of autistic and NT children and adults. Our findings revealed that: (i) autistic individuals either showed similar or worse performance than NT individuals on the pitch tasks; (ii) cognitive abilities were associated with some pitch task performance; and (iii) cognitive abilities modulated the relationship between autism diagnosis and pitch perception on some tasks. Our findings highlight the importance of taking an individual differences approach to understand the strengths and weaknesses of pitch processing in autism.

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22. Rodin RE, Dou Y, Kwon M, Sherman MA, D’Gama AM, Doan RN, Rento LM, Girskis KM, Bohrson CL, Kim SN, Nadig A, Luquette LJ, Gulhan DC, Park PJ, Walsh CA. Author Correction: The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing. Nature neuroscience. 2023.

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23. Rong Y. Comprehension of Spatial Demonstratives in Mandarin-speaking Children on the Autism Spectrum: The Roles of Theory of Mind and Executive Function. Journal of autism and developmental disorders. 2023.

The present study aimed to examine whether Mandarin-speaking children on the autism spectrum showed differences in comprehending spatial demonstratives (« this » and « that », and « here » and « there »), as compared to typically developing (TD) children. Another aim of this study was to investigate the roles of theory of mind (ToM) and executive functions (EF) in the comprehension of spatial demonstratives. Twenty-seven autistic children (mean age 6.86) and 27 receptive-vocabulary-matched TD children (mean age 5.82) were recruited. Demonstrative comprehension was assessed based on participants’ ability to place objects in certain locations according to experimenters’ instructions which involved these demonstratives in three different conditions (same-, opposite-, and spectator-perspective conditions). Four false-belief tasks were administered to measure ToM, and the word-span task and the dimensional change card sort task were used to measure two subcomponents of EF – working memory and mental flexibility – respectively. Children on the autism spectrum were found to score below TD children in the comprehension of spatial demonstratives. In addition, the results showed that ToM and working memory were conducive to the correct interpretation of spatial demonstratives. The two cognitive abilities mutually influenced their respective roles in spatial demonstrative comprehension in the three different conditions. The findings suggest that the comprehension of spatial demonstratives comprehension is an area of need in Mandarin-speaking children on the autism spectrum, and it might be linked to their differences in cognitive abilities.

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24. Siracusano M, Arturi L, Riccioni A, Noto A, Mussap M, Mazzone L. Metabolomics: Perspectives on Clinical Employment in Autism Spectrum Disorder. International journal of molecular sciences. 2023; 24(17).

Precision medicine is imminent, and metabolomics is one of the main actors on stage. We summarize and discuss the current literature on the clinical application of metabolomic techniques as a possible tool to improve early diagnosis of autism spectrum disorder (ASD), to define clinical phenotypes and to identify co-occurring medical conditions. A review of the current literature was carried out after PubMed, Medline and Google Scholar were consulted. A total of 37 articles published in the period 2010-2022 was included. Selected studies involve as a whole 2079 individuals diagnosed with ASD (1625 males, 394 females; mean age of 10, 9 years), 51 with other psychiatric comorbidities (developmental delays), 182 at-risk individuals (siblings, those with genetic conditions) and 1530 healthy controls (TD). Metabolomics, reflecting the interplay between genetics and environment, represents an innovative and promising technique to approach ASD. The metabotype may mirror the clinical heterogeneity of an autistic condition; several metabolites can be expressions of dysregulated metabolic pathways thus liable of leading to clinical profiles. However, the employment of metabolomic analyses in clinical practice is far from being introduced, which means there is a need for further studies for the full transition of metabolomics from clinical research to clinical diagnostic routine.

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25. Stone LE, Kelly MP, Alexander M, Brandel M, Lam SK, Ravindra VM. Rett Syndrome-Associated Scoliosis: Analysis of National Trends and Treatment Patterns of a Rare Indication for Posterior Instrumented Fusion. Spine. 2023.

STUDY DESIGN: Retrospective database cohort study. OBJECTIVE: To evaluate U.S. treatment trends and inpatient outcomes for children undergoing posterior spinal fusion (PSF) for Rett syndrome (RTT)-associated scoliosis (RAS). SUMMARY OF BACKGROUND DATA: RTT is a rare, sporadic neurodevelopmental disorder presenting in childhood with developmental regression, ataxia, and seizures. RAS occurs in 50-80% of cases of RTT, but little is known about the case volume and perioperative experience for children undergoing PSF. METHODS: Using International Classification of Diseases (ICD)-9 and ICD-10 codes in the national Kids’ Inpatient Database, we identified children with RTT who underwent PSF in 2000-2019. Annual case volumes were analyzed. Clinical characteristics and outcomes were compared with those of a cohort of patients with neuromuscular scoliosis (NMS). RESULTS: Among 220 patients with RAS, 216 (98.2%) were female (mean age at surgery 12.3±3.3 y). Surgical case incidence steadily increased over 19 years, with more RAS admissions in the South (31.4%). Overall, patients with RAS demonstrated a higher mean Elixhauser Comorbidity Index score (2 vs. 1, P<0.001) and had more perioperative complications (41.4% vs. 18%, P<0.001) than patients with NMS. RTT diagnosis independently predicted higher odds of any complications (OR 1.98, P<0.001) and increased length of stay (OR 1.18, P=0.009) for admissions for PSF. CONCLUSIONS: Surgical treatment for RAS is rare but increased over a 19-year period. Cases appear to be clustering by region, with the highest proportion in the South. The higher Elixhauser Comorbidity Index in RAS patients predicted higher cost, longer hospital stay, more complications (particularly respiratory), and more nonroutine discharge disposition than in other NMS patients. RTT was independently associated with higher odds of complications and longer length of stay. Because RAS cases appear to be increasing in number, future study should emphasize methods to reduce morbidity and investigate deformity-specific metrics to help better understand this population.

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26. Subri S, Palumbo L, Gowen E. Symmetry Detection in Autistic Adults Benefits from Local Processing in a Contour Integration Task. Journal of autism and developmental disorders. 2023.

Symmetry studies in autism are inconclusive possibly due to different types of stimuli used which depend on either local or global cues. Therefore, this study compared symmetry detection between 20 autistic and 18 non-autistic adults matched on age, IQ, gender and handedness, using contour integration tasks containing open and closed contours that rely more on local or global processing respectively. Results showed that the autistic group performed equally well with both stimuli and outperformed the non-autistic group only for the open contours, possibly due to a different strategy used in detecting symmetry. However, there were no group differences for the closed contour. Results explain discrepant findings in previous symmetry studies suggesting that symmetry tasks that favour a local strategy may be advantageous for autistic individuals. Implications of the findings towards understanding visual sensory issues in this group are discussed.

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27. Sun X, Zhang T, Tong B, Cheng L, Jiang W, Sun Y. POGZ suppresses 2C transcriptional program and retrotransposable elements. Cell reports. 2023; 42(8): 112867.

The POGZ gene has been found frequently mutated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability (ID). We have recently shown that POGZ maintains mouse embryonic stem cells (ESCs). However, the exact mechanisms remain unclear. Here, we show that POGZ plays an important role in the maintenance of ESCs by silencing Dux and endogenous retroviruses (ERVs). POGZ maintains a silent chromatin state at Dux and ERVs by associating with and recruiting TRIM28 and SETDB1, and its loss leads to decreased levels of H3K9me3/H4K20me3, resulting in up-regulation of 2C transcripts and ESC transition to a 2C-like state. POGZ suppresses different classes of ERVs through direct (IAPEy, the intracisternal A-type particle elements) and indirect regulation (MERVL). Activation of POGZ-bound ERVs is associated with up-regulation of nearby neural disease genes such as Serpina3m. Our findings provide important insights into understanding the disease mechanism caused by POGZ dysfunction.

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28. Suzuki N, Hirai M. Autistic traits associated with dichotomic thinking mediated by intolerance of uncertainty. Scientific reports. 2023; 13(1): 14049.

A recent cognitive model suggests that autistic individuals may experience dichotomous thinking patterns mediated by intolerance of uncertainty; however, empirical evidence to support this model is lacking. This study aimed to identify the relationships between autistic traits, intolerance of uncertainty, and dichotomous thinking using the Autism Spectrum Quotient, Short Intolerance of Uncertainty Scale, and the Dichotomous Thinking Inventory. We collected data from non-clinical university students (N = 151; pilot study) and general adults (N = 500; main study) and analyzed the results using structural equation modeling. Both studies showed a significant indirect effect of autistic traits on dichotomous thinking mediated by intolerance of uncertainty. Moreover, the results indicated that intolerance of uncertainty was significantly and positively associated with Autism Spectrum Quotient and Dichotomous Thinking Inventory scores. Conversely, there was a significant negative direct association between Autism Spectrum Quotient and Dichotomous Thinking Inventory scores. This is the first study to demonstrate that autistic traits can result in dichotomous thinking through intolerance of uncertainty. These findings provide insight into the cognitive patterns of autistic individuals.

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29. Uljarević M, Frazier TW, Chetcuti L. Asperger syndrome and clinical heterogeneity: Reflections on the past, present, and future. Developmental medicine and child neurology. 2023.

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30. Viktorsson C, Bölte S, Falck-Ytter T. How 18-month-olds with Later Autism Look at Other Children Interacting: The Timing of Gaze Allocation. Journal of autism and developmental disorders. 2023.

When observing other people during naturally paced and dynamic interactions, it is essential to look at specific locations at the right time to extract a maximum of socially informative content. In this study, we aimed to investigate the looking behavior of typically developing toddlers and toddlers later diagnosed with autism when observing other children interact. The sample consisted of 98 toddlers; 22 in a low-likelihood of autism group, 60 in an elevated likelihood of autism group who did not receive a subsequent diagnosis, and 16 in an elevated likelihood group who did receive an autism diagnosis. Participants performed an eye tracking task at 18 months of age and were assessed for diagnostic outcome at 36 months. The video stimuli consisted of two children interacting, where a boy reaches out for a toy and a girl refuses to give it to him. The low likelihood group showed an expected increase in ratio of looking at the girl’s face after the boy requested the toy, as compared to before (t(21) = -3.337, p = .003). Toddlers with later autism showed a significantly lower ratio of looking at the girl’s face during this time window, as compared to the other groups (F(2,91) = 3.698, p = .029). These findings provide new leads on how social gaze may be different in children with autism in everyday life (e.g., kindergarten), and highlight the need of studying the dynamics of gaze on short time scales.

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31. Winden KD, Pham TT, Teaney NA, Ruiz J, Chen R, Chen C, Sahin M. Increased degradation of FMRP contributes to neuronal hyperexcitability in tuberous sclerosis complex. Cell reports. 2023; 42(8): 112838.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder, but new therapies have been impeded by a lack of understanding of the pathological mechanisms. Tuberous sclerosis complex (TSC) and fragile X syndrome are associated with alterations in the mechanistic target of rapamycin (mTOR) and fragile X messenger ribonucleoprotein 1 (FMRP), which have been implicated in the development of ASD. Previously, we observed that transcripts associated with FMRP were down-regulated in TSC2-deficient neurons. In this study, we find that FMRP turnover is dysregulated in TSC2-deficient rodent primary neurons and human induced pluripotent stem cell (iPSC)-derived neurons and is dependent on the E3 ubiquitin ligase anaphase-promoting complex. We also demonstrate that overexpression of FMRP can partially rescue hyperexcitability in TSC2-deficient iPSC-derived neurons. These data indicate that FMRP dysregulation represents an important pathological mechanism in the development of abnormal neuronal activity in TSC and illustrate a molecular convergence between these two neurogenetic disorders.

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32. Yasuda Y, Matsumoto J, Miura K, Hasegawa N, Hashimoto R. Correction: Genetics of autism spectrum disorders and future direction. Journal of human genetics. 2023.

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33. Zahorodny W, Shenouda J, Sidwell K, Verile MG, Alvarez CC, Fusco A, Mars A, Waale M, Gleeson T, Burack G, Zumoff P. Prevalence and Characteristics of Adolescents with Autism Spectrum Disorder in the New York-New Jersey Metropolitan Area. Journal of autism and developmental disorders. 2023.

PURPOSE: Almost all epidemiologic studies estimating autism spectrum disorder (ASD) prevalence have focused on school-age children. This study provides the first population-based data on the prevalence and expression of ASD among adolescents in a large US metropolitan region. METHODS: Active multiple source ASD surveillance of adolescents aged 16-years was conducted according to the Autism and Developmental Disabilities Monitoring (ADDM) Network method in a four-county New Jersey metropolitan region. Prevalence estimates are provided, characteristics are described and comparison of the distribution and characteristics of ASD is offered for this cohort, at 8 and 16-years. RESULTS: ASD prevalence was 17.7 per 1000 (95% CI: 16.3-19.2)]. One-in-55 males and one in 172 females were identified with ASD. High-SES was positively associated with ASD and White adolescents had higher ASD prevalence (22.2 per 1000) than Hispanic adolescents (13.1 per 1000). One in four study-confirmed individuals with ASD did not have an ASD diagnosis. A majority of ASD adolescents (58.8%) had a co-occurring neuropsychiatric disorder. White and High-SES individuals had greater likelihood of co-occurring disorder. The demographic distribution and functional profile of ASD was similar in this cohort at 8 and 16-years. CONCLUSION: Approximately one-in-55 adolescents in our area had ASD, in 2014, and one-in-4 16-year-olds with ASD was not diagnosed. A majority (3-in-5) of the adolescents with ASD had a co-occurring neuropsychiatric disorder. ASD under-identification and the high frequency of co-disorders in adolescents with ASD pose significant challenges to care and support.

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34. Zhang X, Song XK, So WC. Examining Phenotypical Heterogeneity and its Underlying Factors in Gesture Skills of Chinese Autistic Children: Clustering Analysis. Journal of autism and developmental disorders. 2023.

PURPOSE: The heterogeneity of autism is well documented, but few studies have studied the heterogeneity of gesture production ability in autistic children. The present study aimed to identify subgroups of autistic children who displayed heterogeneous gesture production abilities and explore the underlying factors, including autism characteristics, intellectual ability, and language ability, that were associated with the heterogeneity. METHODS: A total of 65 Chinese autistic children (mean age = 5;3) participated. Their autism characteristics and intellectual ability were assessed by standardized measurements. Language output and gesture production were captured from a parent-child interaction task. RESULTS: We conducted a hierarchical cluster analysis and identified four distinct clusters. Cluster 1 and Cluster 2 both had low gesture production whereas Cluster 3 and Cluster 4 had high gesture production. Both Clusters 1 and 2 had relatively strong autism characteristics, in comparison to Clusters 3 and 4. CONCLUSIONS: Our findings revealed that children with stronger autism characteristics may gesture less often than those with weaker characteristics. However, the relationship between language ability and intellectual ability and gesture production was not clear. These findings shed light on the directions of intervention on gesture production for autistic children, especially those with stronger autism characteristics.

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