1. Alsayouf HA. Growing evidence of pharmacotherapy effectiveness in managing attention-deficit/hyperactivity disorder in young children with or without autism spectrum disorder: a minireview. Front Psychiatry. 2024; 15: 1408876.

Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD.

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2. Barón-Mendoza I, Martínez-Marcial M, García-Juárez M, Mejía-Hernández M, Cortés-Sánchez Y, Zamora-Sánchez CJ, García-Rebollar JO, Chavira-Ramírez R, Ordaz-Rosado D, Camacho-Arroyo I, Tecamachalzi-Silvarán MB, Montes-Narváez O, González-Flores O, García-Becerra R, González-Arenas A. Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism. Horm Behav. 2024; 164: 105593.

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

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3. Bloemert H, Sizoo BB, Verhoeven EWM, Beekman A, van Meijel B. Recovery of adults with autism spectrum disorder during intensive inpatient treatment: a qualitative study. Front Psychiatry. 2024; 15: 1383138.

INTRODUCTION: Although some adults with autism spectrum disorder (ASD) require intensive and specialized ASD treatment, there is little research on how these adults experience the recovery process. Recovery is defined as the significant improvement in general functioning compared to the situation prior to treatment. METHODS: This qualitative study describes the recovery process from the perspective of adults on the autism spectrum during intensive inpatient treatment. Semi-structured interviews (n = 15) were carried out and analyzed according to the principles of grounded theory. RESULTS: Our results indicate that, given the specific characteristics of autism, therapeutic interventions and goal-oriented work cannot be carried out successfully, and the recovery process cannot begin, if no good working relationship has been established, and if care is not organized in ways that a person on the autism spectrum finds clear and predictable.

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4. Chakrabarty D, Arora N, Muneer Ahmed I, Satish S. An Objective Comparison of the Quality and Reliability of Information Regarding Autism Spectrum Disorder on YouTube. Cureus. 2024; 16(5): e60904.

YouTube serves as a good source of information on autism; however, the reliability and quality of such content remain uncertain. This study aimed to evaluate the reliability and quality of autism-related information presented in YouTube videos using the Global Quality Score (GQS) and Reliability Score. Methods: A cross-sectional observational study was conducted in November 2023. A total of 48 autism-related videos on YouTube were sourced using keywords such as ‘autism’, ‘autism cause’, ‘autism treatment’, and ‘autism kids’. The authors then viewed the videos and collected data regarding the number of views, likes and comments, uploader type, and type of information disseminated. The authors also used The GQS and modified DISCERN score to assess the quality and reliability of information in the videos. The data was then subjected to statistical analysis using the Kruskal-Wallis test and IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). Results: Out of 48 videos, seven videos were excluded, leaving 41 for analysis. The included videos amassed 25,540,635 views, 304,557 likes, and 37,039 comments. The majority of videos were uploaded by hospitals (n=15; 36.59%), followed by news channels (n=12; 29.27%). Most videos described autism symptoms (n=26; 63.41%), with fewer addressing potential etiology (n=16; 39.02%). The median GQS was highest for videos uploaded by healthcare professionals (n=5), contrasting with news channels. The Kruskal-Wallis test revealed significant differences (p=0.02). Conclusion: These videos collectively garnered substantial viewership, likes, and comments. Most videos described autism symptoms, although fewer addressed potential causes. Notably, videos uploaded by healthcare professionals achieved the highest GQSs, highlighting their significance in disseminating reliable autism information. Healthcare professionals therefore play a crucial role in disseminating reliable autism information via YouTube. Encouraging their involvement in creating informative videos can enhance public understanding of autism.

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5. Davis AM, Burks-Abbott G, Merecias O, Swenor BK. Autism interventions designed or adapted for the Black/African American population: A systematic review. Autism. 2024: 13623613241259910.

Black/African American people in the United States who have a diagnosis of autism often experience service-related disparities, including not having the same access to high-quality autism and related care (e.g. behavioral interventions), and are less likely to have sustained treatment engagement across their lifespan. While interventions to support autistic people are typically designed to be universal, there is concern that these interventions not being tailored to the Black/African American population could reduce the overall impact due to a lack of responsiveness to the needs of the Black children or families who receive the intervention. The current systematic review summarized research on interventions developed for the Black autism community, including Black children with autism and their caregivers. After a comprehensive, systematic search, eight peer-reviewed publications were identified that met the study’s inclusion criteria. The majority of the interventions were tailored to Black caregivers of children with autism. Autism researchers demonstrate different strategies for engaging Black caregivers in culturally responsive ways; however, more research into these interventions is needed in order to assess their effectiveness. In addition, there are still limited interventions adapted to be culturally responsive to Black/African American autistic people. The Cultural Adaptation Checklist framework is a novel approach with promise to become the standard for adapting interventions to meet the needs of culturally diverse groups. Cultural responsiveness is an important facet in the development of interventions that produce optimal outcomes for the range of diversity in the United States and is an important step to achieving equitable autism research practices.

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6. Deng J, Labarta-Bajo L, Brandebura AN, Kahn SB, Pinto AFM, Diedrich JK, Allen NJ. Suppression of astrocyte BMP signaling improves fragile X syndrome molecular signatures and functional deficits. bioRxiv. 2024.

Fragile X syndrome (FXS) is a monogenic neurodevelopmental disorder with manifestations spanning molecular, neuroanatomical, and behavioral changes. Astrocytes contribute to FXS pathogenesis and show hundreds of dysregulated genes and proteins; targeting upstream pathways mediating astrocyte changes in FXS could therefore be a point of intervention. To address this, we focused on the bone morphogenetic protein (BMP) pathway, which is upregulated in FXS astrocytes. We generated a conditional KO (cKO) of Smad4 in astrocytes to suppress BMP signaling, and found this lessens audiogenic seizure severity in FXS mice. To ask how this occurs on a molecular level, we performed in vivo transcriptomic and proteomic profiling of cortical astrocytes, finding upregulation of metabolic pathways, and downregulation of secretory machinery and secreted proteins in FXS astrocytes, with these alterations no longer present when BMP signaling is suppressed. Functionally, astrocyte Smad4 cKO restores deficits in inhibitory synapses present in FXS auditory cortex. Thus, astrocytes contribute to FXS molecular and functional phenotypes, and targeting astrocytes can mitigate FXS symptoms.

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7. Domellöf E, Hjärtström H, Johansson AM, Rudolfsson T, Stillesjö S, Säfström D. Brain activations during execution and observation of visually guided sequential manual movements in autism and in typical development: A study protocol. PLoS One. 2024; 19(6): e0296225.

Motor issues are frequently observed accompanying core deficits in autism spectrum disorder (ASD). Impaired motor behavior has also been linked to cognitive and social abnormalities, and problems with predictive ability have been suggested to play an important, possibly shared, part across all these domains. Brain imaging of sensory-motor behavior is a promising method for characterizing the neurobiological foundation for this proposed key trait. The present functional magnetic resonance imaging (fMRI) developmental study, involving children/youth with ASD, typically developing (TD) children/youth, and neurotypical adults, will investigate brain activations during execution and observation of a visually guided, goal-directed sequential (two-step) manual task. Neural processing related to both execution and observation of the task, as well as activation patterns during the preparation stage before execution/observation will be investigated. Main regions of interest include frontoparietal and occipitotemporal cortical areas, the human mirror neuron system (MNS), and the cerebellum.

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8. Elliott SA, Rahman S, Scott SD, Craig WR, Knisley L, Shearer K, Hartling L. Seeking Care for Children with Intellectual and/or Developmental Disabilities in the Emergency Department: A Mixed Methods Systematic Review of Parents’ Experiences and Information Needs. Open Access Emerg Med. 2024; 16: 117-31.

The objective of this review was to explore parents’ experiences and information needs regarding management of their child with an intellectual and/or developmental disability (IDD) in the emergency department (ED). We searched six electronic databases and grey literature to identify primary studies in English published since 2000. We synthesized quantitative and qualitative outcome data simultaneously using a convergent integrated approach and used a Mixed Methods Appraisal Tool (MMAT) to assess methodological quality of the included studies. Nine articles derived from seven studies were included (3 qualitative, 3 quantitative, 1 mixed method). Four main themes related to parents’ self-reported experiences were identified: 1) appropriateness of the ED to manage and support their child; 2) acknowledgement/recognition of their child’s IDD and incorporation of those considerations into overall care and management; 3) managing and navigating the ED environment; and 4) decision to disclose their child’s condition when visiting the ED. Two articles provided data relevant to information needs, highlighting parents’ desire to have resources supporting ED orientation and access to services within and outside of the ED setting. From the limited number of studies, it was evident that parents wanted better communication with healthcare providers and a greater understanding by ED staff around physical space settings needed to support their child. Resources supporting ED staff and parents to communicate effectively and work together can ensure that children with IDDs care needs are met. Further research into understanding parents’ experiences and information needs related to managing a child with an IDD in the ED is needed to guide the development of effective resources.

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9. Ham LM, Staunton H, Schulz JM, Tillmann J, Volz D, Murtagh L, Chatham C, O’Connor EC, Chamberlain S, Schoenenberger P, Pandina G, Wang P, Kas MJH, Arango C, Murphy D. Points to consider when initiating clinical investigations in autistic paediatric populations-A White Paper. Eur Neuropsychopharmacol. 2024; 86: 35-42.

Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD.

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10. Jyonouchi H. Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic. Front Psychiatry. 2024; 15: 1333717.

Autism spectrum disorder (ASD(1)) is a behaviorally defined syndrome encompassing a markedly heterogeneous patient population. Many ASD subjects fail to respond to the 1(st) line behavioral and pharmacological interventions, leaving parents to seek out other treatment options. Evidence supports that neuroinflammation plays a role in ASD pathogenesis. However, the underlying mechanisms likely vary for each ASD patient, influenced by genetic, epigenetic, and environmental factors. Although anti-inflammatory treatment measures, mainly based on metabolic changes and oxidative stress, have provided promising results in some ASD subjects, the use of such measures requires the careful selection of ASD subjects based on clinical and laboratory findings. Recent progress in neuroscience and molecular immunology has made it possible to allow re-purposing of currently available anti-inflammatory medications, used for autoimmune and other chronic inflammatory conditions, as treatment options for ASD subjects. On the other hand, emerging anti-inflammatory medications, including biologic and gate-keeper blockers, exert powerful anti-inflammatory effects on specific mediators or signaling pathways. It will require both a keen understanding of the mechanisms of action of such agents and the careful selection of ASD patients suitable for each treatment. This review will attempt to summarize the use of anti-inflammatory agents already used in targeting ASD patients, and then emerging anti-inflammatory measures applicable for ASD subjects based on scientific rationale and clinical trial data, if available. In our experience, some ASD patients were treated under diagnoses of autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. However, there are little clinical trial data specifically for ASD subjects. Therefore, these emerging immunomodulating agents for potential use for ASD subjects will be discussed based on preclinical data, case reports, or data generated in patients with other medical conditions. This review will hopefully highlight the expanding scope of immunomodulating agents for treating neuroinflammation in ASD subjects.

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11. Luo J, Luo Y, Zhao M, Liu Y, Liu J, Du Z, Gong H, Wang L, Zhao J, Wang X, Gu Z, Zhao W, Liu T, Fan X. Fullerenols Ameliorate Social Deficiency and Rescue Cognitive Dysfunction of BTBR T(+)Itpr3(tf)/J Autistic-Like Mice. Int J Nanomedicine. 2024; 19: 6035-55.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T(+)Itpr3(tf)/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments. METHODS: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining. RESULTS: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX(+) and SOX2(+)/GFAP(+) cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment. CONCLUSION: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.

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12. Meeder R, Peterson A, Reynard H, Andersen L. Dyadic Work in Conjunction With Electroconvulsive Therapy in a 12-Year-Old Female With Autism Spectrum Disorder and Catatonia. Ochsner J. 2024; 24(2): 141-6.

Background: Attachment-based interventions have been extensively studied in neurotypical patient populations. In neurodivergent patient populations, however, emphasis on and current research into attachment-based interventions are centered on early childhood. Minimal research has been conducted in school-aged children with autism spectrum disorder (ASD), and even less research has focused on attachment-based interventions for children with significant comorbidities such as catatonia. Case Report: We present the case of a 12-year-old female that involved dyadic work in conjunction with biologic interventions for the treatment of ASD and catatonia. Psychosocial interventions were centered on an attachment-based framework and behavioral skills training that incorporated elements of parent management training. We observed and tracked the patient’s uncooperativeness, underproductive speech, emotional withdrawal, and anxiety via the Brief Psychiatric Rating Scale for Children. Attachment- and behavioral-based interventions in conjunction with psychotropic medications and electroconvulsive therapy resulted in improvements. Conclusion: This case illustrates the potential advantages that attachment- and behavioral-based psychotherapeutic interventions can confer in complex cases involving neurodivergent patients. The case also highlights the lack of current research into and understanding of attachment theory in children and adolescents with ASD. Research is needed into the role of attachment-based interventions in patients with ASD and other psychiatric comorbidities, particularly in patient populations beyond preschool age. Initiating nonbiologic interventions in conjunction with biologic interventions may also enhance outcomes and warrants further investigation.

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13. Meguid NA, Hemimi M, Rashad M, Elsaeid A, Elpatrik G, Zeidan HM. Dysregulation of miR-146a in human milk of mothers having children with autism. Int J Dev Neurosci. 2024.

Autism spectrum disorder (ASD) is a set of neurobehavioral manifestations that impose poor social interaction and stereotyped repetitive patterns. Several mircoRNA (miRNA) dysregulations underpin ASD pathophysiology via impairing the neurogenic niches. For instance, miR-146a and miR-106 differential expressions are linked to deregulation of ASD-related genes and the severity of clinical symptoms, respectively. Breastfeeding provides newborns with many bioactive compounds that support their neurodevelopment including miRNA. Our pilot study evaluated the expression pattern of miR-106a and miR-146a in human milk (HM) of nursing mothers (n = 36) having autistic children compared to age-matched counterparts (n = 36) with neurotypical children as controls. Under sterile conditions, breast milk samples were collected using manual sucking pumps and centrifuged to separate the fat layer. Total RNA was extracted from the lipid fraction, and the expression profiles of both miR-106a and miR-146a were evaluated using quantitative real-time polymerase chain reaction. Among the test group, we reported some factors that were previously linked to HM miRNA perturbations: gestational diabetes, hypertension, and cesarean delivery. HM miR-106a showed comparable expression levels in both mother groups (p = 0.8681), whereas HM miR-146a was significantly downregulated in mothers with autistic children compared to controls (p = 0.0399). Alternatively, HM miR-106 levels were positively associated with two ASD clinical parameters: Childhood Autism Rating Scale (CARS) and communication and language domain of Autism Diagnostic Interview-Revised (ADI-R) (r = 0.6452, p = 0.0003 and r = 0.3958, p = 0.0410, respectively). The receiver operating characteristic (ROC) curves of both maternal HM miR-106a and miR-146a showed poor fitness as predictive biomarkers for ASD. Our findings suggest that the miR-146a differential expression in ASD children may originate at infancy during the lactation period. Thus, maternal pre- and postnatal health care is critical to maintain optimal miRNome in breast milk.

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14. Percy AK, Neul JL, Benke TA, Berry-Kravis EM, Glaze DG, Marsh ED, An D, Bishop KM, Youakim JM. Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study. Med. 2024.

BACKGROUND: Trofinetide was approved for the treatment of Rett syndrome based on the results of the phase 3, randomized, placebo-controlled, 12-week LAVENDER study. Rett syndrome is a chronic disorder requiring long-term treatment. We report the efficacy and safety results of LILAC, a 40-week, open-label extension study of LAVENDER. METHODS: Females with Rett syndrome aged 5-21 years received open-label treatment with trofinetide for 40 weeks. The primary endpoint was long-term safety of trofinetide; secondary endpoints included the change from baseline at week 40 in the Rett Syndrome Behaviour Questionnaire score and the Clinical Global Impression-Improvement score at week 40. FINDINGS: Overall, 154 participants were enrolled and treated with trofinetide in LILAC. The most common adverse events in LILAC were diarrhea (74.7%), vomiting (28.6%), and COVID-19 (11.0%). Diarrhea was the most common adverse event leading to treatment withdrawal (21.4%). The Rett Syndrome Behaviour Questionnaire mean score (standard error) improvement from the LAVENDER baseline to week 40 in LILAC was -7.3 (1.62) and -7.0 (1.61) for participants treated with trofinetide and placebo in LAVENDER, respectively. Mean Clinical Global Impression-Improvement scores (standard error) at week 40 rated from the LILAC baseline were 3.1 (0.11) and 3.2 (0.14) for participants treated with trofinetide and placebo in LAVENDER, respectively. CONCLUSIONS: Treatment with trofinetide for ≤40 weeks continued to improve symptoms of Rett syndrome. Trofinetide had a similar safety profile in LILAC as in LAVENDER. FUNDING: The study was supported by Acadia Pharmaceuticals Inc. (San Diego, CA, USA). This trial was registered at ClinicalTrials.gov (NCT04279314).

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15. Pomè A, Zimmermann E. Visuo-motor updating in individuals with heightened autistic traits. Elife. 2024; 13.

Autism spectrum disorder (ASD) presents a range of challenges, including heightened sensory sensitivities. Here, we examine the idea that sensory overload in ASD may be linked to issues with efference copy mechanisms, which predict the sensory outcomes of self-generated actions, such as eye movements. Efference copies play a vital role in maintaining visual and motor stability. Disrupted efference copies hinder precise predictions, leading to increased reliance on actual feedback and potential distortions in perceptions across eye movements. In our first experiment, we tested how well healthy individuals with varying levels of autistic traits updated their mental map after making eye movements. We found that those with more autistic traits had difficulty using information from their eye movements to update the spatial representation of their mental map, resulting in significant errors in object localization. In the second experiment, we looked at how participants perceived an object displacement after making eye movements. Using a trans-saccadic spatial updating task, we found that those with higher autism scores exhibited a greater bias, indicating under-compensation of eye movements and a failure to maintain spatial stability during saccades. Overall, our study underscores efference copy’s vital role in visuo-motor stability, aligning with Bayesian theories of autism, potentially informing interventions for improved action-perception integration in autism.

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16. Salmerón AM, Pérez-Fernández C, Abreu AC, Fernández S, Tristán AI, Ruiz-Sobremazas D, Cabré M, Guardia-Escote L, Fernández I, Sánchez-Santed F. Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats. Toxicology. 2024; 506: 153871.

Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.

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17. Sandbank M, Pustejovsky JE, Bottema-Beutel K, Caldwell N, Feldman JI, Crowley LaPoint S, Woynaroski T. Determining Associations Between Intervention Amount and Outcomes for Young Autistic Children: A Meta-Analysis. JAMA Pediatr. 2024.

IMPORTANCE: Health professionals routinely recommend intensive interventions (ie, 20-40 hours per week) for autistic children. However, primary research backing this recommendation is sparse and plagued by methodological flaws. OBJECTIVE: To examine whether different metrics of intervention amount are associated with intervention effects on any developmental domain for young autistic children. DATA SOURCES: A large corpus of studies taken from a recent meta-analysis (with a search date of November 2021) of early interventions for autistic children. STUDY SELECTION: Studies were eligible if they reported a quasi-experimental or randomized clinical trial testing the effects of a nonpharmacological intervention on any outcome in participant samples comprising more than 50% autistic children 8 years or younger. DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by multiple coders. Meta-regression models were constructed to determine whether each index of intervention amount was associated with effect sizes for each intervention type, while controlling for outcome domain, outcome proximity, age of participants, study design, and risk of detection bias. Data were analyzed from June 2023 to February 2024. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MAIN OUTCOMES AND MEASURES: The primary predictor of interest was intervention amount, quantified using 3 different metrics (daily intensity, duration, and cumulative intensity). The primary outcomes of interest were gains in any developmental domain, quantified by Hedges g effect sizes. RESULTS: A total of 144 studies including 9038 children (mean [SD] age, 49.3 [17.2] months; mean [SD] percent males, 82.6% [12.7%]) were included in this analysis. None of the meta-regression models evidenced a significant, positive association between any index of intervention amount and intervention effect size when considered within intervention type. CONCLUSIONS AND RELEVANCE: Findings of this meta-analysis do not support the assertion that intervention effects increase with increasing amounts of intervention. Health professionals recommending interventions should be advised that there is little robust evidence supporting the provision of intensive intervention.

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18. Schmidt RJ, Goodrich AJ, Delwiche L, Hansen RL, Simpson CL, Tancredi D, Volk HE. Newborn Dried Blood Spot Folate in Relation to Maternal Self-reported Folic Acid Intake, Autism Spectrum Disorder, and Developmental Delay. Epidemiology. 2024; 35(4): 527-41.

BACKGROUND: Maternal folic acid intake has been associated with decreased risk for neurodevelopmental disorders including autism spectrum disorder (ASD). Genetic differences in folate metabolism could explain some inconsistencies. To our knowledge, newborn folate concentrations remain unexamined. METHODS: We measured folate in archived newborn dried blood spots of children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) case-control study who were clinically confirmed at 24-60 months to have ASD (n = 380), developmental delay (n = 128), or typical development (n = 247). We quantified monthly folic acid intake from maternally-reported supplements and cereals consumed during pregnancy and 3 months prior. We assessed associations of newborn folate with maternal folic acid intake and with ASD or developmental delay using regression. We stratified estimates across maternal and child MTHFR genotypes. RESULTS: Among typically developing children, maternal folic acid intake in prepregnancy and each pregnancy month and prepregnancy prenatal vitamin intake were positively associated with newborn folate. Among children with ASD, prenatal vitamin intake in pregnancy months 2-9 was positively associated with newborn folate. Among children with developmental delay, maternal folic acid and prenatal vitamins during the first pregnancy month were positively associated with neonatal folate. Associations differed by MTHFR genotype. Overall, neonatal folate was not associated with ASD or developmental delay, though we observed associations with ASD in children with the MTHFR 677 TT genotype (odds ratio: 1.76, 95% CI = 1.19, 2.62; P for interaction = 0.08). CONCLUSION: Maternal prenatal folic acid intake was associated with neonatal folate at different times across neurodevelopmental groups. Neonatal folate was not associated with reduced ASD risk. MTHFR genotypes modulated these relationships.

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19. Vasudevan V, Nagel A, Thompson LA. What Parents Need to Know About Autism Screening and Early Treatment. JAMA Pediatr. 2024.

This JAMA Pediatrics Patient Page describes autism screening for children and how to access therapies. eng.

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20. Xu G, Geng G, Wang A, Li Z, Liu Z, Liu Y, Hu J, Wang W, Li X. Three autism subtypes based on single-subject gray matter network revealed by semi-supervised machine learning. Autism Res. 2024.

Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network’s topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case-control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.

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21. Yang X, Li H, Yang C, Ge J. Supplementation with stigma maydis polysaccharide attenuates autism-like behaviors and improves gut function in valproic acid-induced autism model male rats. Int J Dev Neurosci. 2024.

Stigma maydis polysaccharide (SMPS) has regulatory effect on the intestinal microflora and promotes gastrointestinal peristalsis. Children with autism spectrum disorder (ASD) often experience gastrointestinal problems and dysbiosis in their gut microbiota. Our previous study revealed that SMPS interventions had an impact on the gut microbiota of valproic acid (VPA)-induced autism model rats. However, the effects of SMPS on the behavior and gut function of autism model rats remain poorly understood. Therefore, we gave different doses of SMPS intervention in the early stage of autism model rats to observe their developmental conditions and behavior performances. Through histological evaluation and real-time polymerase chain reaction (PCR), integrity of the intestinal structure and the expression of tight junction-related gene Zo-1 and Occludin were detected. The results indicated that SMPS intervention improved the physical development, learning and memory impairment, and social performance of autism model rats. Meanwhile, SMPS promoted intestinal peristalsis and restored the integrity of the intestinal structure, reduced the number of inflammatory cells, and increased the expression of the Zo-1 and Occludin genes. Furthermore, the expression levels of neurotransmitters (substance P, enkephalin, vasoactive intestinal peptide, and 5-hydroxytryptamine) in the hippocampal tissues were altered after SMPS treatment. In conclusion, SMPS could ameliorate ASD-like phenotypes and gut problems in autism model rats. Collectively, these results provide new evidence for the relationship between the gut-brain axis and ASD and suggest a novel therapeutic target for ASD treatment.

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