1. Al-Enezi E, Alghamdi M, Al-Enezi K, AlBalwi M, Davies W, Eyaid W. Correction: Helsmoortel-Van der Aa syndrome in a 13-year-old girl with autistic spectrum disorder, dysmorphism, a right solitary kidney, and polycystic ovaries: a case report. J Med Case Rep. 2024; 18(1): 505.

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2. Alves CL, Martinelli T, Sallum LF, Rodrigues FA, Toutain T, Porto JAM, Thielemann C, Aguiar PMC, Moeckel M. Multiclass classification of Autism Spectrum Disorder, attention deficit hyperactivity disorder, and typically developed individuals using fMRI functional connectivity analysis. PLoS One. 2024; 19(10): e0305630.

Neurodevelopmental conditions, such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), present unique challenges due to overlapping symptoms, making an accurate diagnosis and targeted intervention difficult. Our study employs advanced machine learning techniques to analyze functional magnetic resonance imaging (fMRI) data from individuals with ASD, ADHD, and typically developed (TD) controls, totaling 120 subjects in the study. Leveraging multiclass classification (ML) algorithms, we achieve superior accuracy in distinguishing between ASD, ADHD, and TD groups, surpassing existing benchmarks with an area under the ROC curve near 98%. Our analysis reveals distinct neural signatures associated with ASD and ADHD: individuals with ADHD exhibit altered connectivity patterns of regions involved in attention and impulse control, whereas those with ASD show disruptions in brain regions critical for social and cognitive functions. The observed connectivity patterns, on which the ML classification rests, agree with established diagnostic approaches based on clinical symptoms. Furthermore, complex network analyses highlight differences in brain network integration and segregation among the three groups. Our findings pave the way for refined, ML-enhanced diagnostics in accordance with established practices, offering a promising avenue for developing trustworthy clinical decision-support systems.

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3. Avalos LA, Oberman N, Alexeeff SE, Croen LA, Davignon MN, Adams SR, Ansley D, Chambers CD, Steuerle K, Young-Wolff KC. Early Maternal Prenatal Cannabis Use and Child Developmental Delays. JAMA Netw Open. 2024; 7(10): e2440295.

IMPORTANCE: Maternal prenatal cannabis use is associated with adverse neonatal health effects, yet little is known about its association with child developmental outcomes. OBJECTIVE: To evaluate associations between maternal prenatal cannabis use in early pregnancy and child early developmental delays. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 119 976 children born to 106 240 unique individuals between January 2015 and December 2019 and followed up to aged 5.5 years or younger (through December 31, 2021) at Kaiser Permanente Northern California. Individuals were screened for prenatal cannabis use via self-report and urine toxicology at entrance into prenatal care (approximately 8- to 10-weeks’ gestation). Data were analyzed from February 2023 to March 2024. EXPOSURE: Maternal prenatal cannabis use defined as any use (self-reported or by urine toxicology testing) and use frequency. MAIN OUTCOMES: Early developmental delays (speech and language disorders, motor delays, global delays) in children up to age 5.5 years defined by International Statistical Classification of Diseases and Related Health Problems, Ninth Revision and Tenth Revision diagnoses codes ascertained from electronic health records. RESULTS: In this cohort of 119 976 pregnancies among 106 240 unique pregnant individuals, there were 29 543 Hispanic pregnancies (24.6%), 6567 non-Hispanic Black pregnancies (5.5%), 46 823 non-Hispanic White pregnancies (39.0%), 12 837 pregnancies (10.7%) to individuals aged 24 years or younger, and 10 365 pregnancies (8.6%) to individuals insured by Medicaid. Maternal prenatal cannabis use was documented for 6778 pregnancies (5.6%). Daily maternal prenatal cannabis use was reported for 618 pregnancies (0.5%), weekly for 722 pregnancies (0.6%), and monthly or less for 1617 pregnancies (1.3%). No association was observed between maternal prenatal cannabis use and child speech and language disorders (HR, 0.93; 95% CI, 0.84-1.03), global developmental delays (HR, 1.04; 95% CI, 0.68-1.59), or motor delays (HR, 0.86; 95% CI, 0.69-1.06). No association was detected between the frequency of maternal prenatal cannabis use and child early developmental delays. CONCLUSIONS AND RELEVANCE: In this cohort study, maternal prenatal cannabis use was not associated with an increased risk of child early developmental delays. Future research is needed to assess different patterns of cannabis use throughout pregnancy. Given the association between maternal prenatal cannabis use and other adverse outcomes, pregnant individuals should be educated on those risks.

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4. Avalos LA, Shenkute M, Alexeeff SE, Oberman N, Croen LA, Davignon M, Adams SR, Ansley D, Castellanos C, Young-Wolff KC. Maternal Prenatal Cannabis Use and Child Autism Spectrum Disorder. JAMA Netw Open. 2024; 7(10): e2440301.

IMPORTANCE: Despite an increase in maternal prenatal cannabis use and associations with adverse neonatal outcomes, research on child neurodevelopmental outcomes is limited. OBJECTIVE: To evaluate the association between maternal cannabis use in early pregnancy and child autism spectrum disorder (ASD). DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective birth cohort study included children born between 2011 and 2019 to pregnant Kaiser Permanente Northern California members screened for prenatal cannabis use during pregnancy. Statistical analysis was conducted February 2023 to March 2024. EXPOSURES: Maternal prenatal cannabis use was assessed at entrance to prenatal care (approximately 8- to 10-weeks’ gestation) via self-report and/or positive urine toxicology test. Use frequency was assessed. MAIN OUTCOMES AND MEASURES: Child ASD was defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes ascertained from the electronic health record. Associations between maternal prenatal cannabis use and child ASD were modeled using Cox proportional hazards regression adjusted for maternal sociodemographic, other substance use and disorders, prenatal care initiation, comorbidities, and clustering among maternal siblings. RESULTS: The study cohort included 178 948 singleton pregnancies among 146 296 unique pregnant individuals, including 48 880 (27.3%) Asian or Pacific Islander, 42 799 (23.9%) Hispanic, 9742 (5.4%) non-Hispanic Black, and 70 733 (39.5%) non-Hispanic White pregnancies. The median (IQR) maternal age at pregnancy onset was 31 (6) years; 8486 (4.7%) screened positive for cannabis use, 7054 (3.9%) via urine toxicology testing and 3662 (2.0%) by self-report. In the total study population, the frequency of self-reported use was monthly or less for 2003 pregnancies (1.1%), weekly for 918 pregnancies (0.5%), daily for 741 pregnancies (0.4%), and unknown for 4824 pregnancies (2.7%). ASD was diagnosed in 3.6% of children. After adjustment for maternal characteristics, maternal prenatal cannabis use was not associated with child ASD (hazard ratio [HR], 1.05; 95% CI, 0.84-1.32). When self-reported frequency of use was assessed, no statistically significant associations were observed after confounder adjustment. No sex-specific associations were documented (males: HR, 1.01; 95% CI, 0.77-1.32; and females: HR, 1.19; 95% CI, 0.77-1.85). CONCLUSIONS AND RELEVANCE: In this cohort study, maternal cannabis use assessed in early pregnancy was not associated with child ASD. Additional studies are needed to evaluate different patterns of use throughout pregnancy. Given the known adverse neonatal health effects of maternal prenatal cannabis use, clinicians should follow national guidelines and advise against use.

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5. Bilder DA, Sullivan S, Hughes MM, Dalton S, Hall-Lande J, Nicholls C, Bakian AV. Regional differences in autism and intellectual disability risk associated with cesarean section delivery. Autism Res. 2024.

Prior epidemiological studies investigating the association between delivery mode (i.e., vaginal birth and cesarean section [C-section]) and autism spectrum disorder (ASD) and intellectual disability (ID) risk have reported mixed findings. This study examined ASD and ID risks associated with primary and repeat C-section within diverse US regions. During even years 2000-2016, 8-years-olds were identified with ASD and/or ID and matched to birth records [ASD only (N = 8566, 83.6% male), ASD + ID (N = 3445, 79.5% male), ID only (N = 6158, 60.8% male)] using the Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring Network methodology. The comparison birth cohort (N = 1,456,914, 51.1% male) comprised all births recorded in the National Center for Health Statistics corresponding to birth years and counties in which surveillance occurred. C-section rates in the birth cohort demonstrated significant regional variation with lowest rates in the West. Overall models demonstrate increased odds of disability associated with primary and repeat C-section. Adjusted models, stratified by region, identified significant variability in disability likelihood associated with repeat C-section: increased odds occurred for all case groups in the Southeast, for ASD only and ID only in the Mid-Atlantic, and no case groups in the West. Regional variability in disability risk associated with repeat C-section coincides with differences in birth cohorts’ C-section rates. This suggests increased likelihood of disability is not incurred by the procedure itself, but rather C-section serves as a proxy for exposures with regional variability that influence fetal development and C-section rates.

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6. Du G, Guo Y, Xu W. The effectiveness of applied behavior analysis program training on enhancing autistic children’s emotional-social skills. BMC Psychol. 2024; 12(1): 568.

BACKGROUND: This study focuses on the potential of Applied Behavior Analysis (ABA) to improve emotional and social skills in children with autism spectrum disorder. ABA is a well-established therapeutic approach that uses behavior modification techniques to encourage positive behaviors and reduce challenging ones. Despite its widespread use, further research is needed to better understand its specific impact on emotional and social development in autistic children. OBJECTIVE: This research aims to investigate an effective method for improving and enhancing institutionalized children’s social, communicative, and daily life skills. The study also examines the impact of behavioral analysis on these children’s social and emotional skills. METHOD: The research is categorized as applied in terms of objectives and quasi-experimental in data collection. It involves a control group, an experimental group, and a covariance analysis model. The research population consists of 100 volunteer boys aged 4 to 11 residing in institutional care in Wuhan during the year 2023. Among them, 60 individuals were selected and divided into control and experimental groups, each comprising 30 participants. Data for the study were collected using the kindergarten inventory of social/ emotional tendencies (KIST. The applied behavioral analysis program was implemented individually for the experimental group in eight one-hour sessions twice a week. FINDINGS: Data analysis was conducted using SPSS-24 software and a multivariate analysis of the covariance method. The results indicated that the behavioral analysis program significantly impacts institutionalized children’s social and communicative skills, improving their daily lives (p < .05). CONCLUSION: The findings of this study demonstrate that the applied behavior analysis program significantly improves the social, communicative, and daily life skills of institutionalized children with autism spectrum disorder. ABA interventions, delivered through structured sessions, effectively enhance emotional and social development, confirming its value as a therapeutic approach in institutional care settings.

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7. Dutta AK. Variable expressivity of Malan syndrome. BMJ Case Rep. 2024; 17(10).

We describe the family of a patient with developmental delay, macrocephaly, dysmorphic facial features and autism. His mother also shared similar facial features and macrocephaly but not his neurobehavioural issues. Subsequently, both the child and his mother were found to have a heterozygous frameshift variant NFIX: c.34_41dupGGGATACC. The child and his mother had many features consistent with a genetic diagnosis of Malan syndrome. Therefore, this family highlighted the variable expressivity of Malan syndrome.

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8. Edwards C, Love AM, Flower RL, Ying Cai R, Gibbs V. ‘Just knowing it’s there gives me comfort’: Exploring the benefits and challenges of autism alert cards. Autism. 2024: 13623613241286025.

This study looks at how people use and feel about autism alert cards, which help Autistic people communicate their diagnosis/identity. We surveyed 272 Australian people, including 136 Autistic adults, 128 parents of Autistic children and eight Autistic children. About half of the participants used the card after ordering it, mostly in public places such as public transport, healthcare settings and in retail settings. People found the card helpful because it made it easier to explain their needs without having to speak and provided them a sense of security. However, some people treated Autistic people poorly after being shown the card due to a lack of understanding about autism. Many participants felt that more education about autism is needed to improve how people react to the alert card. Despite these challenges, most participants (76.2%) would recommend the alert card to others. This research shows that while autism alert cards can be very helpful, their effectiveness depends on how well other people understand and accept autism. To make these cards work better, we need more training and awareness programmes for the general public and professionals such as doctors or police officers who may interact with Autistic people.

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9. Gong M, Li J, Qin Z, Machado Bressan Wilke MV, Liu Y, Li Q, Liu H, Liang C, Morales-Rosado JA, Cohen ASA, Hughes SS, Sullivan BR, Waddell V, van den Boogaard MH, van Jaarsveld RH, van Binsbergen E, van Gassen KL, Wang T, Hiatt SM, Amaral MD, Kelley WV, Zhao J, Feng W, Ren C, Yu Y, Boczek NJ, Ferber MJ, Lahner C, Elliott S, Ruan Y, Mignot C, Keren B, Xie H, Wang X, Popp B, Zweier C, Piard J, Coubes C, Mau-Them FT, Safraou H, Innes AM, Gauthier J, Michaud JL, Koboldt DC, Sylvie O, Willems M, Tan WH, Cogne B, Rieubland C, Braun D, McLean SD, Platzer K, Zacher P, Oppermann H, Evenepoel L, Blanc P, El Khattabi L, Haque N, Dsouza NR, Zimmermann MT, Urrutia R, Klee EW, Shen Y, Du H, Rappaport L, Liu CM, Chen X. MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway. Am J Hum Genet. 2024.

Microtubule affinity-regulating kinase 2 (MARK2) contributes to establishing neuronal polarity and developing dendritic spines. Although large-scale sequencing studies have associated MARK2 variants with autism spectrum disorder (ASD), the clinical features and variant spectrum in affected individuals with MARK2 variants, early developmental phenotypes in mutant human neurons, and the pathogenic mechanism underlying effects on neuronal development have remained unclear. Here, we report 31 individuals with MARK2 variants and presenting with ASD, other neurodevelopmental disorders, and distinctive facial features. Loss-of-function (LoF) variants predominate (81%) in affected individuals, while computational analysis and in vitro expression assay of missense variants supported the effect of MARK2 loss. Using proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs), we show that MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and dis-organization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2(+/-) mice showed abnormal cortical formation and partition and ASD-like behavior. Through the use of RNA sequencing (RNA-seq) and lithium treatment, we link MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identify lithium as a potential drug for treating MARK2-associated ASD.

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10. Gündoğmuş E, Bumin G, Yalçın SS. Effect of Early Intervention on Developmental Domains and Parent-Child Interaction Among Children With Developmental Delay: A Randomized Controlled Study. Am J Occup Ther. 2024; 78(6).

IMPORTANCE: The scope of early intervention (EI) programs, which mostly focus on motor skills, needs to be expanded. OBJECTIVE: To examine the effects of an EI on developmental domains and parent-child interactions. DESIGN: Randomized controlled study. PARTICIPANTS: Children ages 24-36 mo with developmental delay (DD; intervention group, n = 30; control group, n = 40). SETTING: Pediatric occupational therapy unit of Hacettepe University. INTERVENTION: The intervention group received an intervention that used the Goal Activity and Motor Enrichment (GAME) approach and a home program, whereas the control group received a home program only. Both groups received the same intervention dosage. OUTCOMES AND MEASURES: Developmental domains were assessed using the Bayley Scales of Infant and Toddler Development Third Edition (Bayley III) and the Ages and Stages Questionnaires (ASQ). Sensory processing was assessed with the Infant/Toddler Sensory Profile 2 (ITSP-2), social-emotional development with the ASQ:Social-Emotional (ASQ:SE), and parent-child interaction with the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO™). A compliance checklist was used to determine compliance with the home program. RESULTS: A significant between-groups difference was found on all Bayley III and PICCOLO subscales and on the Gross Motor, Fine Motor, Problem-Solving, and Social-Emotional domains of the ASQ and ASQ:SE in favor of the intervention group (p < .05). The intervention group showed more typification (normal sensory processing) in sensory quadrants and general processing. Both groups were 100% compliant with the home program. CONCLUSIONS AND RELEVANCE: The GAME-based intervention for children with DD, including sensory and cognitive activities, is effective in improving developmental domains and parent-child interactions. Plain-Language Summary: The scope of early intervention programs mostly focuses on motor skills and needs to be expanded to include the essential roles of children's sensory and cognitive abilities. This study provides important insights into early interventions by occupational therapists and the impact on children with developmental delay and parent-child interactions. We found that the Goal Activity and Motor Enrichment (GAME) intervention for children with developmental delay, which includes sensory and cognitive activities, is effective in improving developmental domains and parent-child interactions.

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11. Ishido M, Higashi K, Mori H, Ueno M, Kurokawa K. DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: comparison with valproate model rats of autism. Behav Brain Res. 2024: 115293.

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8~11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4(th) generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7 to 8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

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12. Kim HW, Kim JH, Chung US, Kim JI, Shim SH, Park TW, Lee MS, Hwang JW, Park EJ, Hwang SK, Joung YS. AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial. Psychiatry Clin Neurosci. 2024.

AIM: This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children. METHODS: This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12. RESULTS: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea. CONCLUSIONS: Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD.

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13. Kim S, Jung HT, Thao SK. Communication, Socialization, and Literacy for Adults With Developmental Disabilities: An Interview Study of Parents’ Perspectives and Experiences. Am J Speech Lang Pathol. 2024: 1-18.

PURPOSE: The study highlights the significance of continuous support and services in communication, socialization, and literacy skills for adults with developmental disabilities (DDs). The aim of the study was to gather in-depth information on the individualized needs, lived experiences, and expectations of adults with DD by interviewing their parents. METHOD: A total of 14 parents of adults with DD participated in one-on-one semistructured interviews. During the interviews, parents were asked to describe (a) their children’s current communication, socialization, reading and writing skills; (b) the types of communication, socialization, and literacy support their children were receiving; and (c) the types of support that their children needed. Interviews were video- and audio-recorded, transcribed, and analyzed qualitatively using thematic analysis. RESULTS: Thematic analysis revealed three main themes and eight subthemes: (1) insufficient support and services for adults with DD (i.e., lack of competent professionals and lack of literacy support), (2) approaches that the parents attempted for their children with DD (i.e., parents’ responsibilities, technologies, and pseudoscience), and (3) recommendations for ongoing support and services (i.e., novel technologies, social media, and motivation). CONCLUSIONS: The study highlights crucial gaps between the participating parents’ desire for individualized, consistent, and innovative support and services for their adult children with DD and scarcity of resources in communication, socialization, and literacy. The dearth of evidence-based support and resources leads to easy access to pseudoscience. Future research is warranted to develop innovative, customized, and highly motivating programs in communication, socialization, and literacy for adults with DD. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27214407.

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14. Koh SH. Analyzing the influence of physical exercise interventions on social skills in children with autism spectrum disorder: insights from meta-analysis. Front Psychol. 2024; 15: 1399902.

INTRODUCTION: Children diagnosed with autism spectrum disorder (ASD) commonly encounter difficulties in social interactions and communication, significantly affecting their overall wellbeing. One proposed strategy to address these challenges is through physical exercise interventions. This study aims to conduct a meta-analysis to assess the impact of physical exercise interventions on the social skills of children with ASD. METHODS: To perform this meta-analysis, we followed the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) Statement and the practical guide for transparent reporting of systematic reviews. Eligible studies included randomized controlled trials or quasi-experimental studies investigating the effects of physical exercise interventions on social skills among children with ASD. We used the standardized mean difference (SMD) to measure effect size. RESULTS: Sixteen studies were included in the meta-analysis. The results indicated a significant improvement in social skills among children with ASD following physical exercise interventions (SMD = -0.54, 95% CI = [-0.63; -0.44]). The moderator analysis underscored the crucial role of age in explaining the intervention outcomes for enhancing social skills, with interventions lasting more than 12 weeks recommended for better social skills improvement. DISCUSSION: The findings of this meta-analysis provide robust evidence supporting the efficacy of physical exercise interventions in enhancing the social skills of children with ASD. The moderator analysis underscores the importance of considering both the mean age and duration of interventions when implementing such programs. These results underscore the significance of physical exercise as a viable option for improving social skills in this population.

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15. Lord L, Rogers J, Gamble GD, Harding JE. Are toddlers with neurosensory impairment more difficult to follow up? A secondary analysis of the hPOD follow-up study. Arch Dis Child Fetal Neonatal Ed. 2024; 109(6): 643-51.

OBJECTIVE: To describe strategies used to maximise follow-up after a neonatal randomised trial, how these differed for families of different ethnicity, socioeconomic status and urban versus rural residence and investigate relationships between the difficulty of follow-up and rate of neurosensory impairment. METHOD: hPOD was a multicentre randomised trial assessing oral dextrose gel prophylaxis for neonatal hypoglycaemia. Follow-up at 2 years was conducted from 2017 to 2021. We analysed all recorded contacts between the research team and participants’ families. Neurosensory impairment was defined as blindness, deafness, cerebral palsy, developmental delay or executive function impairment. RESULTS: Of 1321 eligible participants, 1197 were assessed (91%) and 236/1194 (19.8%) had neurosensory impairment. Participants received a median of five contacts from the research team (range 1-23). Those from more deprived areas and specific ethnicities received more contacts, particularly home tracking visits and home assessments. Impairment was more common among participants receiving more contacts (relative risk 1.81, 95% CI 1.34 to 2.44 for ≥7 contacts vs <7 contacts), and among those assessed after the intended age (76/318, 23.9% if >25 months vs 160/876, 18.3% if ≤25 months). CONCLUSIONS: Varied contact strategies and long timeframes are required to achieve a high follow-up rate. Without these, the sociodemographics of children assessed would not have been representative of the entire cohort, and the rate of neurosensory impairment would have been underestimated. To maximise follow-up after randomised trials, substantial effort and resources are needed to ensure that data are useful for clinical decision-making.

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16. Matsui M, Lynch LE, Distefano I, Galante A, Gade AR, Wang HG, Gómez-Banoy N, Towers P, Sinden DS, Wei EQ, Barnett AS, Johnson K, Lima R, Rubio-Navarro A, Li AK, Marx SO, McGraw TE, Thornton PS, Timothy KW, Lo JC, Pitt GS. Multiple beta cell-independent mechanisms drive hypoglycemia in Timothy syndrome. Nat Commun. 2024; 15(1): 8980.

The canonical G406R mutation that increases Ca(2+) influx through the CACNA1C-encoded Ca(V)1.2 Ca(2+) channel underlies the multisystem disorder Timothy syndrome (TS), characterized by life-threatening arrhythmias. Severe episodic hypoglycemia is among the poorly characterized non-cardiac TS pathologies. While hypothesized from increased Ca(2+) influx in pancreatic beta cells and consequent hyperinsulinism, this hypoglycemia mechanism is undemonstrated because of limited clinical data and lack of animal models. We generated a Ca(V)1.2 G406R knockin mouse model that recapitulates key TS features, including hypoglycemia. Unexpectedly, these mice do not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. Patient data confirm the absence of hyperinsulinism. We discover multiple alternative contributors, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic control of glucose homeostasis. These data provide new insights into contributions of Ca(V)1.2 channels and reveal integrated consequences of the mutant channels driving life-threatening events in TS.

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17. Meng J, Pan P, Guo G, Chen A, Meng X, Liu H. Transient CSF1R inhibition ameliorates behavioral deficits in Cntnap2 knockout and valproic acid-exposed mouse models of autism. J Neuroinflammation. 2024; 21(1): 262.

Microglial abnormality and heterogeneity are observed in autism spectrum disorder (ASD) patients and animal models of ASD. Microglial depletion by colony stimulating factor 1-receptor (CSF1R) inhibition has been proved to improve autism-like behaviors in maternal immune activation mouse offspring. However, it is unclear whether CSF1R inhibition has extensive effectiveness and pharmacological heterogeneity in treating autism models caused by genetic and environmental risk factors. Here, we report pharmacological functions and cellular mechanisms of PLX5622, a small-molecule CSF1R inhibitor, in treating Cntnap2 knockout and valproic acid (VPA)-exposed autism model mice. For the Cntnap2 knockout mice, PLX5622 can improve their social ability and reciprocal social behavior, slow down their hyperactivity in open field and repetitive grooming behavior, and enhance their nesting ability. For the VPA model mice, PLX5622 can enhance their social ability and social novelty, and alleviate their anxiety behavior, repetitive and stereotyped autism-like behaviors such as grooming and marble burying. At the cellular level, PLX5622 restores the morphology and/or number of microglia in the somatosensory cortex, striatum, and hippocampal CA1 regions of the two models. Specially, PLX5622 corrects neurophysiological abnormalities in the striatum of the Cntnap2 knockout mice, and in the somatosensory cortex, striatum, and hippocampal CA1 regions of the VPA model mice. Incidentally, microglial dynamic changes in the VPA model mice are also reported. Our study demonstrates that microglial depletion and repopulation by transient CSF1R inhibition is effective, and however, has differential pharmacological functions and cellular mechanisms in rescuing behavioral deficits in the two autism models.

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18. Oh M, Yoon NH, Kim SA, Yoo HJ. Epigenetic Insights into Autism Spectrum Disorder: DNA Methylation Levels of NR3C1, ASCL1, and FOXO3 in Korean Autism Spectrum Disorder Sibling Pairs. Clin Psychopharmacol Neurosci. 2024; 22(4): 635-45.

OBJECTIVE: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. METHODS: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such as NR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition. Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires. Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. RESULTS: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. CONCLUSION: This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

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19. Pagán AF, Montenegro MC, Ahlenius M, Ramirez AC, Ortiz M, Bernal E, Montiel-Nava C, Bittner J, Loveland KA, Acierno RE. The Transition to Adulthood: A Qualitative Study of Autism Spectrum Disorder From Military and Veteran Parents and Military-Dependent Young Adults. Mil Med. 2024.

INTRODUCTION: Given the unique experiences of military service members and their families, military-dependent young adults (18-25 years old) with autism spectrum disorder (ASD) and their military or veteran families experience unique barriers to accessing quality mental health care during the transition to adulthood. In fact, developing services to address ASD challenges for military families is a burgeoning area of interest for the department of defense. However, there is a limited knowledge on the specific needs of military families as the young adult’s transition outside of high school and lose supports. MATERIALS AND METHODS: The present study conducted 3 focus groups with 16 military and veteran parents, and 3 focus groups with 10 military-dependent young adults to evaluate the needs of military-dependent young adults (17-25 years old) with ASD and military/veteran parents with a young adult with ASD. RESULTS: Parents reported several key topics, including barriers to services (e.g., permanent change of station, recently moving to a state and lacking awareness of the available resources), defining adulthood in terms working in a cohesive family structure, and therapy recommendations for parents and young adults with ASD transitioning to adulthood. Young adults provided key information, including describing experiences with having a parent in the military, difficulty accessing services during the transition to adulthood, and recommendations on therapy for military-dependent young adults with ASD. CONCLUSION: Military and veteran families with autistic dependents lack access to important mental-health resources. When developing programs for military families and military-dependent autistic young adults, mental health providers should consider the frequent relocations, lack of access to important transition resources, and common military values. The presence of advocates at military bases should be encouraged to help military families navigate autism services in their local community.

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20. Pinyot J, Lacambra D, Garriga M, Pinyot M, Niubó JM. Positional Plagiocephaly Side and Neurodevelopmental Delay: Study on 408 Infants. J Craniofac Surg. 2024; 35(7): 2027-35.

OBJECTIVE: Provide data on a cross-sectional study of neurodevelopmental delays in positional plagiocephaly (PP) based on severity and flattening side on early childhood patients. METHODS: Neurodevelopment of 408 PP in patients with an age range of 3 to 59 months was assessed with Battelle Developmental Inventory (BDI) tests during and after their cranial orthotic treatment. Data obtained were compared with the cranial anthropometric measurements taken the same day the test was made, and results were segregated by flattening side, grouped by diagnosis and severity, segmented by age group, and split by sex. RESULTS: From 3983 patients with positional skull deformities and simple craniosynostosis, 526 patients accepted to participate and took a total of 1261 BDI tests. Premature, patients with neurological diseases, cranial malformations, tests taken when positional skull deformity was corrected, and tests without plagiocephaly were excluded. The resulting database was made of 408 PP patients (300 boys and 108 girls) and 883 BDI tests (345 with left-side plagiocephaly and 538 with right-side plagiocephaly). Significant neurodevelopmental delay in more than one BDI domain on left-side plagiocephaly tests is observed in 76.4% of female and 92.2% of male patients and on right-side plagiocephaly tests in 75.5% of female and 95.5% of male patients. Neurodevelopmental delay difference between flattening sides, when both plagiocephaly sides presented significant delays, ranges from 0.2 to 3 months (BDI domain fine motor, Cephalic Index range ≥85 <100; BDI communication, age group 18-23). CONCLUSION: Neurological delay may vary depending on plagiocephaly side, thus when evaluating plagiocephaly patients the flattening side should be noted.

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21. Poupard L, Page G, Thoreau V, Kaouah Z. Relationships between Gut Microbiota and Autism Spectrum Disorders: Development and Treatment. Clin Psychopharmacol Neurosci. 2024; 22(4): 554-64.

Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.

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22. Quesada JA, Sánchez-Ferrer F, López-Pineda A. Autism Spectrum Disorder and Associated Factors in Children in Spain, 2017: Population-Based Cross-Sectional Study. Matern Child Health J. 2024.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with biological, multicausal and polygenic origins. The true prevalence of ASD has not been clearly established. The aim of this study was to estimate the prevalence of ASD in children aged 3 to 14 years in Spain and to analyze the factors associated with it. METHODS: A cross-sectional observational study using data from the 2017 National Survey of Health in Minors in Spain. Primary outcome was the diagnosis of ASD, and sociodemographic, behavioral, health-related, the use of health services, household and medication use variables was analyzed. Multivariable logistic regression model with a correction for modelling rare events was fitted. Complex sampling was undertaken, using the survey elevation factor in the analysis. RESULTS: A total of 4409 children were included, and there were 26 children with ASD, for a prevalence of 0.59%, representing 29,143 children with ASD. Factors significantly associated were male sex, having visited a psychologist, and/or a speech therapist in the past year, presenting probable problems with peers, antisocial behavior, taking antibiotics and taking other medications. CONCLUSION: The findings of this study may be useful to inform health policies and develop strategic plans to identify and address the needs of children with ASD.

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23. Rawnsley KL, Doyle LW, Anderson PJ, Olsen JE, Kwong AKL, Mainzer RM, Josev EK, Roberts G, Spittle AJ, Cheong JLY. Parent screening questionnaires to detect cognitive and language delay at 2 years in high-risk infants: an analysis from the Victorian Infant Collaborative Study 2016-2017 cohort. Arch Dis Child Fetal Neonatal Ed. 2024; 109(6): 652-6.

OBJECTIVE: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g). DESIGN: Prospective cohort study. SETTING: State of Victoria, Australia. PATIENTS: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2). MAIN OUTCOME MEASURES: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3). RESULTS: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay. CONCLUSIONS: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity.

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24. Ruan M, Zhang N, Yu X, Li W, Hu C, Webster PJ, L KP, Wang S, Li X. Can micro-expressions be used as a biomarker for autism spectrum disorder?. Front Neuroinform. 2024; 18: 1435091.

INTRODUCTION: Early and accurate diagnosis of autism spectrum disorder (ASD) is crucial for effective intervention, yet it remains a significant challenge due to its complexity and variability. Micro-expressions are rapid, involuntary facial movements indicative of underlying emotional states. It is unknown whether micro-expression can serve as a valid bio-marker for ASD diagnosis. METHODS: This study introduces a novel machine-learning (ML) framework that advances ASD diagnostics by focusing on facial micro-expressions. We applied cutting-edge algorithms to detect and analyze these micro-expressions from video data, aiming to identify distinctive patterns that could differentiate individuals with ASD from typically developing peers. Our computational approach included three key components: (1) micro-expression spotting using Shallow Optical Flow Three-stream CNN (SOFTNet), (2) feature extraction via Micron-BERT, and (3) classification with majority voting of three competing models (MLP, SVM, and ResNet). RESULTS: Despite the sophisticated methodology, the ML framework’s ability to reliably identify ASD-specific patterns was limited by the quality of video data. This limitation raised concerns about the efficacy of using micro-expressions for ASD diagnostics and pointed to the necessity for enhanced video data quality. DISCUSSION: Our research has provided a cautious evaluation of micro-expression diagnostic value, underscoring the need for advancements in behavioral imaging and multimodal AI technology to leverage the full capabilities of ML in an ASD-specific clinical context.

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25. Tong J, Chen X, Wang B, Wang T, Wang X, Ma S, Shi D, Wang X, Yan D. Moderating effects of general self-efficacy on courtesy stigma and anxiety and depressive symptoms of parents of children with autism spectrum disorder. Front Psychiatry. 2024; 15: 1454004.

BACKGROUND: Stigma, anxiety and depressive symptoms are highly prevalent in parents of children with autism spectrum disorder (ASD) and may have a detrimental impact on the rehabilitation and treatment of children with ASD, ultimately leading to more behavioral issues and higher rates of disability. Therefore, the purpose of this study was to identify the association between general self-efficacy, courtesy stigma, and anxiety and depressive symptoms, and to further discuss whether general self-efficacy moderated the association between courtesy stigma and anxiety and depressive symptoms in parents of children with ASD. METHODS: A total of 409 parents of children with ASD from Lianyungang, Jiangsu Province, Eastern China participated in a cross-sectional survey. A structured questionnaire was used to collect sociodemographic characteristics, courtesy stigma, general self-efficacy, anxiety symptoms, and depressive symptoms. Hierarchical multiple regression was used to assess the associations of courtesy stigma, general self-efficacy and courtesy stigma × general self-efficacy interaction with anxiety and depressive symptoms. Simple slope analysis was used to visualize the interaction. RESULTS: The courtesy stigma of parents of children with ASD was positively correlated with anxiety (B = 0.374, P < 0.001) and depressive symptoms (B = 0.366, P < 0.001). General self-efficacy was negatively correlated with anxiety (B = -0.200, P < 0.001) and depressive symptoms (B = -0.210, P < 0.001). The association between courtesy stigma and anxiety symptoms was different in the high (1 standard deviation (SD) above the mean, b = 0.258, standard error (SE) = 0.056, t = 4.567, P < 0.001) and low (1 SD below the mean, b = 0.470, SE = 0.053, t = 8.870, P < 0.001) groups of general self-efficacy. In addition, the association between courtesy stigma and depressive symptoms was also different in the high (1 SD above the mean, b = 0.241, SE = 0.056, t = 4.268, P < 0.001) and low (1 SD below the mean, b = 0.469, SE = 0.053, t = 8.844, P < 0.001) groups of general self-efficacy. CONCLUSIONS: General self-efficacy could moderate the impact of courtesy stigma on anxiety and depressive symptoms. Therefore, among parents of children with ASD who experienced high courtesy stigma, enhancing general self-efficacy could be an effective strategy to reduce anxiety and depressive symptoms in this population.

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26. Xiong W, Li X, Huang X, Xu J, Qu Z, Su Y, Li Y, Han Y, Cui T, Zhang X. Impaired motor and social skill development in infancy predict high autistic traits in toddlerhood. Neuroscience. 2024; 558: 114-21.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder. Early diagnosis in the critical period is important for ASD children. Recent studies of neurodevelopmental behavioral features and joint attention in high-risk infants showed there are some special cues which can distinguish ASD from typical development infant. But the findings of high-risk population may not be applicable to the general population. It is necessary to « analogically » study the potential warning traits of ASD in infancy in the general population. We did a nested case-control study from June 2019 to November 2022 in Tianjin, China, including 76 general infants whom completed the neurodevelopmental evaluation, the Checklist for Autism in Toddlers-23 (CHAT-23) screening, and eye tracking task. Social behavior quotient in infancy was negatively correlated to CHAT-23 total scores in toddlerhood. Social behavior quotient in infancy was positively correlated to initiating joint attention in toddlerhood. Regression model showed that high fine motor scale and social behaviour scale quotient in infancy were associated with an decreased risk of the total score of CHAT-23 ≥ 2 in toddlerhood. The Receiver operating characteristic curve showed the social behaviour in infancy alone and the combination of fine motor and social behaviour in infancy contributed to auxiliary diagnosis of higher level of autistic traits in toddlerhood. These findings suggest that Impaired development of fine motor and social behavior in infancy are potential warning features of high autistic traits in general population.

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27. Yeh PW, Chiang CH, Lee CY. Processing of Emotional Words in Children and Adolescents with Autism Spectrum Disorders. J Autism Dev Disord. 2024.

Individuals with autism spectrum disorder (ASD) have difficulties in understanding emotional language, but little research has discussed the developmental course of the processing of emotional words in the clinical population. Previous studies have revealed distinct processing for emotion-label (e.g., happiness) and emotion-laden (e.g., birthday) words in typically developing (TD) children and adolescents. Extending these findings, the study used event-related potentials (ERPs) to explore the processing of these two types of emotional words in children and adolescents with ASD. The stimuli included two-character Chinese words with factors of word type (emotion-label versus emotion-laden) and valence (positive versus negative). The participants were 11 to 14-year-old children and adolescents with ASD (N = 23) and age-matched TD peers (N = 23). They categorized emotion valence for words while their brain responses were recorded. Both the TD and the ASD groups exhibited emotional processing for all emotional words across the N400 and late positivity component (LPC). The emotional processing was modulated by word type but varied with group and valence. A trend for group differences was observed in processing positive words at 500-600 ms. In particular, the emotion effects of positive emotion-label words were positively correlated with social dysfunction across all participants. These findings suggested that children and adolescents with ASD have a selective impairment in understanding emotional concepts from language. The ERP measurements may reflect atypical emotional word processing for individuals with higher autistic severity in positive valence contexts.

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28. Zahedi E, Sadr SS, Sanaeierad A, Hosseini M, Roghani M. Acetyl-l-carnitine alleviates valproate-induced autism-like behaviors through attenuation of hippocampal mitochondrial dysregulation. Neuroscience. 2024; 558: 92-104.

This study aimed to evaluate the potential benefits of acetyl-L-carnitine (ALCAR) in the context of valproate-induced autism. After prenatal exposure to valproate (VPA; 600 mg/kg, i.p.) on embryonic day 12.5, followed by ALCAR treatment (300 mg/kg on postnatal days 21-49, p.o.), assessment of oxidative stress, mitochondrial membrane potential (MMP), mitochondrial biogenesis, parvalbumin interneurons, and hippocampal volume was conducted. These assessments were carried out subsequent to the evaluation of autism-like behaviors. Hippocampal analysis of oxidative factors (reactive oxygen species and malondialdehyde) and antioxidants (superoxide dismutase, catalase, and glutathione) revealed a burden of oxidative stress in VPA rats. Additionally, mitochondrial biogenesis and MMP were elevated, while the number of parvalbumin interneurons decreased. These changes were accompanied by autism-like behaviors observed in the three-chamber maze, marble burring test, and Y-maze, as well as a learning deficit in the Barnes maze. In contrast, administrating ALCAR attenuated behavioral deficits, reduced oxidative stress, improved parvalbumin-positive neuronal population, and properly modified MMP and mitochondrial biogenesis. Collectively, our results indicate that oral administration of ALCAR ameliorates autism-like behaviors, partly through its targeting oxidative stress and mitochondrial biogenesis. This suggests that ALCAR may have potential benefits ASD managing.

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