1. Binder MS, Escobar I, Xu Y, Sokolov AM, Zhang L, Bordey A. Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways. J Neurosci;2024 (Sep 25);44(39)

Communication in the form of nonverbal, social vocalization, or crying is evolutionary conserved in mammals and is impaired early in human infants that are later diagnosed with autism spectrum disorder (ASD). Defects in infant vocalization have been proposed as an early sign of ASD that may exacerbate ASD development. However, the neural mechanisms associated with early communicative deficits in ASD are not known. Here, we expressed a constitutively active mutant of Rheb (Rheb(S16H)), which is known to upregulate two ASD core pathways, mTOR complex 1 (mTORC1) and ERK1/2, in Layer (L) 2/3 pyramidal neurons of the neocortex of mice of either sex. We found that cellular mosaic expression of Rheb(S16H) in L2/3 pyramidal neurons altered the production of isolation calls from neonatal mice. This was accompanied by an expected misplacement of neurons and dendrite overgrowth, along with an unexpected increase in spine density and length, which was associated with increased excitatory synaptic activity. This contrasted with the known decrease in spine density in Rheb(S16H) neurons of 1-month-old mice. Reducing the levels of the actin cross-linking and adaptor protein filamin A (FLNA), known to be increased downstream of ERK1/2, attenuated dendrite overgrowth and fully restored spine properties, synaptic connectivity, and the production of pup isolation calls. These findings suggest that upper-layer cortical pyramidal neurons contribute to communicative deficits in a condition known to affect two core ASD pathways and that these mechanisms are regulated by FLNA.

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2. Dean EE, Hagiwara M, Brunson L, Linnenkamp B, Swindler S, Shogren KA. Self-Advocate and Family Member Experiences With Supported Decision Making. Intellect Dev Disabil;2024 (Oct 1);62(5):392-405.

Supported decision making (SDM) is a needed focus of policy and practice to enhance opportunities for people with disabilities to exercise self-determination as they are supported to make decisions about their life. This study used content analysis to analyze five focus groups comprised of 27 adults with intellectual and developmental disabilities (IDD) and 16 family members to understand how people with IDD use supports for decision making and how families support decision making. People with IDD and family members described a range of strategies and supports they used for decision making, including engaging trusted supporters, accessing technology, and using early experiences to build decision-making skills. Findings from this research can inform development of practices and policy to enhance use of SDM in research, policy, and practice.

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3. Dodds L, Filliter C, Campbell LA, MacDonald NE, Shea S, Dubé E, Smith IM, Mehrabadi A, Filliter JH. Routine vaccine uptake in school-aged autistic and non-autistic youth: A linked database study. Can J Public Health;2024 (Sep 25)

OBJECTIVES: This study was conducted to determine whether school-aged autistic youth received routine vaccines at a lower rate than their non-autistic peers. METHODS: In Nova Scotia (NS), Canada, vaccines routinely delivered in early adolescence are administered to Grade 7 students through a school-based Public Health vaccination program. NS youth eligible to receive Grade 7 vaccinations between 2011 and 2017 were included in this study. Autism spectrum disorder (ASD) diagnoses were determined from administrative health data. Rates of receipt of any Grade 7 vaccine and of individual vaccines were compared between autistic and non-autistic youth. Subgroup analyses included comparing Grade 7 vaccine receipt between autistic youth and their non-autistic siblings and early childhood vaccine receipt between autistic and non-autistic cohorts. RESULTS: The rates of receipt of any vaccine were 73% among 916 autistic youth and 82% among 49,599 non-autistic youth (adjusted relative risk = 0.91; 95% confidence interval = 0.87-0.95). Similar results were found for individual vaccines. Subgroup analyses revealed lower rates of Grade 7 vaccine receipt among autistic youth compared to among their non-autistic siblings. Rates of early childhood vaccine receipt did not differ between autistic and non-autistic cohorts. CONCLUSION: Autistic youth were under-vaccinated compared to their non-autistic peers for Grade 7 vaccinations. Lower vaccination rates in autistic youth than in their non-autistic siblings suggest that setting-related factors may contribute more to the under-vaccination of autistic youth than parental vaccine hesitancy. Barriers to vaccine uptake for school-aged autistic youth, including those unique to school-based vaccination programs, must be explored and addressed.

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4. Feng S, Ding L, Wang M, Zhang J, Yuan Y, Zhang P, Bai X. Can similarity of autistic traits promote neural synchronization?. Exp Brain Res;2024 (Sep 25)

People with similar levels of autistic traits are reported to exhibit better interactions than those with larger differences in autistic traits. However, whether this « similarity effect » exists at the neural level remains unclear. To address this gap, the present study employed functional near-infrared spectroscopy (fNIRS) hyperscanning technology to assess inter-brain synchronization (IBS) during naturalistic conversations among dyads with three types of autistic trait combinations (20 high-high, 22 high-low, and 18 low-low dyads). The results revealed that the high-high dyads exhibited significantly lower IBS in the right temporoparietal junction (rTPJ) region compared to the low-low dyads, with no significant differences observed between the high-low group and the other two groups. Moreover, though dyadic differences in conversation satisfaction were positively correlated with dyadic autistic trait differences, IBS only showed a significant negative correlation with the dyadic average autistic trait scores and no significant correlation with the dyadic difference scores of autistic traits. These findings suggest that dyads with high autistic traits may have shared feelings about conversations, but cannot produce IBS through successful mutual prediction and understanding.

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5. Haber T, Davies L, Hinman RS, Bennell KL, Bruce W, Jewell L, Borda A, Lawford BJ. ‘It’s especially good just to know that you’re not the only one’: a qualitative study exploring experiences with online peer support programmes for the Fragile X community. J Intellect Disabil Res;2024 (Sep 25)

BACKGROUND: Accessing peer support can be difficult for people with, or carers of people with, inherited intellectual disabilities. One way to improve access is to provide services online, yet few studies have explored people’s experiences with online peer support programmes. We aimed to explore experiences with such programmes for communities affected by fragile X-associated conditions. METHODS: Qualitative study involving individual semi-structured interviews with 16 people with, or carers of people with, a fragile X-associated condition (n = 4 adult premutation carriers; n = 12 parents/carers of children/adults), who participated in at least one of three online peer support programmes: educational webinars, Facebook discussion group and small peer group sessions via Zoom. Reflexive thematic analysis was used to develop themes. RESULTS: Three overarching themes relating to experiences were as follows: (1) uncertainty and value of shared experiences, (2) support navigating healthcare, (3) advantages being online, but still a place for in-person events. Educational webinars were perceived to be a valuable source of information about fragile X-associated conditions although people had variable information needs. Facebook discussion groups enabled people to connect with others, although participants expressed some competing preferences for how the groups were organised. Zoom peer group sessions were perceived to help participants feel supported by others, but that consistency in organisation was important. CONCLUSIONS: Online peer support programmes were perceived to be beneficial, bridging informational gaps and facilitating social connection. However, participants believed there was still a place for in-person events, some felt educational webinars did not always meet their needs and some had privacy concerns.

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6. Lakshmi NRA, Deshmukh PR, Tripathy JP, Dahake U. Prevalence and Determinants of Developmental Delay in Children of 12-36 Months in the Area of Primary Health Centre, Bela, Nagpur. Indian J Public Health;2024 (Jul 1);68(3):355-361.

BACKGROUND: Developmental delay happens when a child fails to attain age-appropriate milestones. Identification of developmental delay in children is important to initiate early intervention in them which will facilitate the children to have a productive life in their later years. OBJECTIVES: The objective was to study the prevalence of developmental delay among 12-36-month-old children from the area of Primary Health Centre, Bela, in rural Nagpur, Maharashtra. MATERIALS AND METHODS: This was a community-based cross-sectional study design. A total of 314 children were selected through simple random sampling and assessed for delay using the Pediatric Development Screening Tool (PDST). RESULTS: 14.9% had developmental delay in at least any one domain and 3.5% had global developmental delay. Domain-specific developmental delay was highest for language delay (10%) followed by fine motor (5%). Gross motor and personal social delays had the same prevalence (3.1%). On multivariable lower literacy, level of mother and Composite Index of Anthropometric Failure were significant variables for any developmental delay. Hospitalization of the child during the 1st month of life and lower parenting scores were the significant factors associated with global delay. CONCLUSION: Development delay is present in a sizeable proportion of children <3 years of age which affects their future growth and achievement. We recommend annual community-based screening for delays to detect and manage such children.

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7. Liu H, Huang M, Yu X. Blood and hair copper levels in childhood autism spectrum disorder: a meta-analysis based on case-control studies. Rev Environ Health;2024 (Sep 25);39(3):511-517.

OBJECTIVES: The association between copper levels and autism spectrum disorder (ASD) has been a controversial topic. This study investigated relationship between copper levels and ASD. CONTENT: The following databases are searched until April 2022: PubMed, EMBASE and Web of Science. Combined effect size standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated with Stata 12.0. In this meta-analysis, 29 case-control studies were included, which included 2,504 children with ASD and 2,419 healthy controls. The copper levels in hair (SMD: -1.16, 95% CI: -1.73 to -0.58) was significantly lower in ASD children than healthy controls. The copper levels in blood (SMD: 0.10, 95% CI: -0.12 to 0.32) not significantly compare ASD with controls. SUMMARY AND OUTLOOK: Copper may be associated with the development of ASD in children.

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8. Lu H, Zhang H, Zhong Y, Meng XY, Zhang MF, Qiu T. A machine learning model based on CHAT-23 for early screening of autism in Chinese children. Front Pediatr;2024;12:1400110.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental condition that significantly impacts the mental, emotional, and social development of children. Early screening for ASD typically involves the use of a series of questionnaires. With answers to these questionnaires, healthcare professionals can identify whether a child is at risk for developing ASD and refer them for further evaluation and diagnosis. CHAT-23 is an effective and widely used screening test in China for the early screening of ASD, which contains 23 different kinds of questions. METHODS: We have collected clinical data from Wuxi, China. All the questions of CHAT-23 are regarded as different kinds of features for building machine learning models. We introduce machine learning methods into ASD screening, using the Max-Relevance and Min-Redundancy (mRMR) feature selection method to analyze the most important questions among all 23 from the collected CHAT-23 questionnaires. Seven mainstream supervised machine learning models were built and experiments were conducted. RESULTS: Among the seven supervised machine learning models evaluated, the best-performing model achieved a sensitivity of 0.909 and a specificity of 0.922 when the number of features was reduced to 9. This demonstrates the model’s ability to accurately identify children for ASD with high precision, even with a more concise set of features. DISCUSSION: Our study focuses on the health of Chinese children, introducing machine learning methods to provide more accurate and effective early screening tests for autism. This approach not only enhances the early detection of ASD but also helps in refining the CHAT-23 questionnaire by identifying the most relevant questions for the diagnosis process.

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9. Mady ZM, Abdeldayem TS, Elmwafie SM, Ramadan AS. Effect of a Nurses’ Training Program on Early Detection of Egyptian Children With Developmental Disabilities in Assiut Governorate. Intellect Dev Disabil;2024 (Oct 1);62(5):354-362.

This study aimed to determine the effectiveness of a designed training program for nurses toward early detection of developmental disabilities among children aged 0-3 years. A group of 21 licensed nurses with professional experience ranging from 5-11 years participated in the study. The participants completed the measurements to evaluate their current knowledge, practice, and perception pre- and post-training program, as well as during a follow-up, in relation to early detection of disabilities. The results showed highly statistically significant difference between the studied nurses’ total knowledge, perception, and practice in pre- and post-program application (p = 0.01). However, there was no statistically significant difference between the post-program and follow-up application (p = 0.180).

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10. Mues M, Demurie E, Erdogan M, Schaubroeck S, Krol M, Goodwin A, Buitelaar J, Loth E, Roeyers H. Uh and um in autism: The case of hesitation marker usage in Dutch-speaking autistic preschoolers. J Child Lang;2024 (Sep 25):1-17.

English-speaking autistic children use the hesitation marker um less often than non-autistic children but use uh at a similar rate. It is unclear why this is the case. We employed a sample of Dutch-speaking children from the Preschool Brain Imaging and Behavior Project to examine hesitation markers in autistic and non-autistic preschoolers with the aim to 1) make a crosslinguistic comparison of hesitation marker usage and 2) examine hypotheses regarding the underlying linguistic mechanisms of hesitation markers: the symptom hypothesis and the signal hypothesis. We found initial group differences in all hesitation markers but these results were rendered insignificant after controlling for age, sex and nonverbal cognition. We found significant correlations between hesitation marker usage and expressive and receptive language, but not autism traits. Lastly, we show interesting cross-linguistic differences in hesitation marker usage between Dutch-speaking participants and previously described English-speaking participants, such as a preference for um over uh.

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11. Nakamura T, Sumiyoshi T, Kamio Y, Takahashi H. Reduced multiscale complexity of daily behavioral dynamics in autism spectrum disorder. PCN Rep;2024 (Dec);3(4):e70016.

AIM: Autism spectrum disorder (ASD) is difficult to diagnose objectively due to its heterogeneous and complex manifestations. This study aimed to objectively characterize the behavioral phenotypes of ASD children by exploring the multiscale behavioral dynamics. METHODS: We applied behavioral organization (BO) and multiscale sample entropy (MSE) analyses to physical activity data collected from ASD and typically developing children, using wearable monitors in their daily life. We also examined their correlation with auditory startle response measures and clinical questionnaires, including the Social Responsiveness Scale (SRS) and the Strengths and Difficulties Questionnaire (SDQ). RESULTS: A significant decrease in MSE at timescales longer than 6 min was observed in ASD children, suggesting decreased irregularity or unpredictability, potentially linked to repetitive behaviors or stereotyped patterns commonly observed in ASD. Additionally, an increase in MSE positively correlated with prepulse inhibition levels, indicating its relationship with sensorimotor gating. Moreover, the observed significant negative correlation with the total difficulty score of SDQ substantiates MSE’s potential as an objective metric for assessing general mental health problems associated with ASD. CONCLUSION: Multiscale analysis enhances the understanding of ASD’s behavioral dynamics, providing valuable metrics for real-world assessments.

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12. Pearson JN, Outlaw JK, Stewart-Ginsburg JH, Martin DLM. « I Know How to Get Around Your ‘No' »: A Follow-Up of the FACES Psychoeducational Intervention. Intellect Dev Disabil;2024 (Oct 1);62(5):406-419.

Black children and their families encounter systemic disadvantages in their journey to and through an autism diagnosis. Black families often experience social and systemic barriers to service use. Providing family-centered, psychoeducational interventions can reduce barriers to service access and utilization for Black families raising autistic children. Fostering Advocacy, Communication, Empowerment, and Support (FACES) has demonstrated preliminary efficacy in strengthening outcomes among Black families, yet little is known about the long-term impact of the intervention. The purpose of this qualitative interview study was to understand the experiences of FACES graduates 16 months after the intervention. Four major themes emerged: (a) strengthened advocacy, (b) strengthened empowerment, (c) systemic barriers, and (d) home and community barriers. We provide implications for research and practice.

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13. Santana VS, Marchezan J, Scheibe DB, Bücker J. Emotion Comprehension and Socio-cognitive Skills in Children with High Functioning Autism Spectrum Disorders. Trends Psychiatry Psychother;2024 (Sep 25)

BACKGROUND AND OBJECTIVES: This study aimed to compare socio-cognitive skills and emotion comprehension between children with Autism Spectrum Disorder (ASD) and children with neurotypical development. METHODS: This quantitative, cross-sectional, controlled study involved 19 children in each group, matched by age (6-12 years) and sex. The assessments examined cognitive aspects (Intelligence Quotient was assessed using the Vocabulary and Matrix Reasoning subtests; working memory using the digit span and letter-number sequencing subtests; attention using the Continuous Performance Test – Identical Pairs; and executive functions using the Trail Making Test), social functions (Children’s Social Skills, Behavior Problems, and Academic Competence Inventory), and emotion comprehension (language was assessed using the Strange Stories Test; emotional facial expressions using the digital emotion comprehension test; emotional/affective prosody using the Profiling Elements of Prosody in Speech-Communication – Brazilian Portuguese adapted version). RESULTS: The group with ASD exhibited better performance in executive functions (p=0.02). However, they lagged the control group in social skills (p=0.04), behavior problems (p=0.03), and emotion comprehension (language, facial expressions, and prosody) (all p<0.05). CONCLUSION: The findings indicate that children with ASD have diminished performance in social skills and emotion comprehension compared to children with neurotypical development. Therefore, the development of technologies and/or therapeutic interventions that address these deficits among children with ASD is recommended.

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14. Shen C, Zhu X, Chang H, Li C, Hou M, Chen L, Lu C, Zhou Z, Ji M, Xu Z. The rebalancing of the immune system at the maternal-fetal interface ameliorates autism-like behavior in adult offspring. Cell Rep;2024 (Sep 24);43(10):114787.

Maternal immune activation (MIA) is critical for imparting neuropathology and altered behaviors in offspring; however, maternal-fetal immune cell populations have not been thoroughly investigated in MIA-induced autism spectrum disorders (ASDs). Here, we report the single-cell transcriptional landscape of placental cells in both PBS- and poly(I:C)-induced MIA dams. We observed a decrease in regulatory T (Treg) cells but an increase in the M1 macrophage population at the maternal-fetal interface in MIA dams. Based on the Treg-targeting approach, we investigate an immunoregulatory protein, the helminth-derived heat shock protein 90α (Sjp90α), that induces maternal Treg cells and subsequently rescues the autism-like behaviors in adult offspring. Furthermore, in vivo depletion of maternal macrophages attenuates placental inflammatory reaction and reverses behavioral abnormalities in adult offspring. Notably, Sjp90α induces CD4(+) T cell differentiation via scavenger receptor A (SR-A) on the macrophage in vitro. Our findings suggest a maternal Treg-targeted approach to alleviate MIA-induced autism-like behavior in adult offspring.

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15. Tamaoki Y, Pasapula V, Danaphongse TT, Reyes AR, Chandler CR, Borland MS, Riley JR, Carroll A, Engineer CT. Pairing Tones with Vagus Nerve Stimulation Improves Brainstem Responses to Speech in the Valproic Acid Model of Autism. J Neurophysiol;2024 (Sep 25)

Receptive language deficits and aberrant auditory processing are often observed in individuals with autism spectrum disorders (ASD). Symptoms associated with ASD are observed in rodents prenatally exposed to valproic acid (VPA), including deficits in speech sound discrimination ability. These perceptual difficulties are accompanied by changes in neural activity patterns. In both cortical and subcortical levels of the auditory pathway, VPA-exposed rats have impaired responses to speech sounds. Developing a method to improve these neural deficits throughout the auditory pathway is necessary. The purpose of this study was to investigate the ability of vagus nerve stimulation (VNS) paired with sounds to restore degraded inferior colliculus responses in VPA-exposed rats. VNS paired with the speech sound « dad » was presented to a group of VPA-exposed rats 300 times per day for 20 days. Another group of VPA-exposed rats were presented with VNS paired with multiple tone frequencies for 20 days. The inferior colliculus responses were recorded from 19 saline-exposed control rats, 18 VPA-exposed with no VNS, 8 VNS-speech paired VPA-exposed, and 7 VNS-tone paired VPA-exposed female and male rats. Pairing VNS with tones increased the IC response strength to speech sounds by 44% when compared to VPA-exposed rats alone. Contrarily, VNS-speech pairing significantly decreased the IC response to speech compared with VPA-exposed rats by 5%. The current research indicates that pairing VNS with tones improved sound processing in rats exposed to VPA and suggests that auditory processing can be improved through targeted plasticity.

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16. Yang K, Li T, Geng Y, Zhang R, Xu Z, Wu J, Yuan Y, Zhang Y, Qiu Z, Li F. Protocol for the neonatal intracerebroventricular delivery of adeno-associated viral vectors for brain restoration of MECP2 for Rett syndrome. STAR Protoc;2024 (Sep 25);5(4):103344.

Here, we present a protocol for neonatal intracerebroventricular (ICV) delivery of adeno-associated viral vectors (AAVs), achieving gene therapy for a Rett syndrome mouse model. We describe steps for preparing mouse lines, replacing foster mothers, sex typing, and genotyping. We then detail procedures for ICV delivery and validation through immunofluorescent and immunoblot techniques. This protocol is also applicable to preclinical gene therapy research that targets the neonatal mouse brain for other neurodevelopmental disorders. For complete details on the use and execution of this protocol, please refer to Yang et al.(1).

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