1. Alhusain AF, Mahmoud MA, Alhamami HN, Ebrahim Alobid S, Ansari MA, Ahmad SF, Nadeem A, Bakheet SA, Harisa GI, Attia SM. Salubrious effects of proanthocyanidins on behavioral phenotypes and DNA repair deficiency in the BTBR mouse model of autism. Saudi Pharm J;2024 (Nov);32(11):102187.

Autism is a neurodevelopmental disorder distinguished by impaired social interaction and repetitive behaviors. Global estimates indicate that autism affects approximately 1.6% of children, with the condition progressively becoming more prevalent over time. Despite noteworthy progress in autism research, the condition remains untreatable. This serves as a driving force for scientists to explore new approaches to disease management. Autism is linked to elevated levels of oxidative stress and disturbances in the DNA repair mechanism, which may potentially play a role in its comorbidities development. The current investigation aimed to evaluate the beneficial effect of the naturally occurring flavonoid proanthocyanidins on the behavioral characteristics and repair efficacy of autistic BTBR mice. Moreover, the mechanisms responsible for these effects were clarified. The present findings indicate that repeated administration of proanthocyanidins effectively reduces altered behavior in BTBR animals without altering motor function. Proanthocyanidins decreased oxidative DNA strand breaks and accelerated the rate of DNA repair in autistic animals, as evaluated by the modified comet test. In addition, proanthocyanidins reduced the elevated oxidative stress and recovered the disrupted DNA repair mechanism in the autistic animals by decreasing the expressions of Gadd45a and Parp1 levels and enhancing the expressions of Ogg1, P53, and Xrcc1 genes. This indicates that proanthocyanidins have significant potential as a new therapeutic strategy for alleviating autistic features.

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2. Amini-Khoei H, Taei N, Dehkordi HT, Lorigooini Z, Bijad E, Farahzad A, Madiseh MR. Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic-Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress. Phytother Res;2024 (Nov 4)

A confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early-life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51-53 to PND 58-60. Behavioral experiments, including the Morris water maze, three-chamber test, shuttle box, and resident-intruder test, were conducted post-treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic-like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF-α, and IL-1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti-inflammatory and antioxidant properties.

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3. Bitsika V, Sharpley CF, Vessey KA, Evans ID. Prevalence, Symptom Profiles, and Correlates of Mixed Anxiety-Depression in Male and Female Autistic Youth. NeuroSci;2024 (Sep);5(3):315-327.

Relatively little attention has been given to mixed anxiety and depression in autistic youth, particularly how this differs between males and females. This study investigated sex-based differences in the prevalence and correlates of mixed anxiety and depression in a sample of 51 autistic males (M age = 10.16 yr, SD = 2.81 yr, and range = 6 yr to 17 yr) and 51 autistic females (M age = – 10.07 yr, SD = 2.76 yr, and range = 6 yr to 17 yr), matched for age, IQ, and autism severity. Self-reports on generalised anxiety disorder and major depressive disorder, morning salivary cortisol, ADOS-2 scores, and WASI-II full-scale scores were collected from these autistic youth, and data on the ASD-related symptoms of these youth were collected from their parents. The data were analysed for total anxiety-depression score levels, for the underlying components of this scale, and for the individual items used in the scale. The results indicate no significant sex differences for the prevalence of mixed anxiety and depression total scores or the underlying components of anxiety and depression or for the individual items of the mixed anxiety-depression scale. There were sex differences in the significant correlates of mixed anxiety and depression: morning cortisol and ASD-related difficulties in social interaction for females, and ASD-related behaviour for males. Males’ feelings of being restless or edgy were correlated with their social interaction and repetitive and restricted behaviour. Females’ difficulties in social interaction were correlated with their concerns about their abilities and their sleeping problems. Females’ sleeping problems, their tendency to talk about dying, and feeling worthless, were correlated with their morning cortisol. These findings suggest that, while mixed anxiety and depression is experienced similarly by autistic males and females at the global, component, and individual item levels, specific aspects of the symptomatology of mixed anxiety and depression are differently associated with aspects of their ASD-related symptomatology and their levels of chronic physiological stress for males and females.

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4. Bou Najm D, Alame S, Takash Chamoun W. Unraveling the Role of Wnt Signaling Pathway in the Pathogenesis of Autism Spectrum Disorder (ASD): A Systematic Review. Mol Neurobiol;2024 (Nov 4)

Autism spectrum disorder (ASD), or simply autism, is a neurodevelopmental disorder characterized by social communication deficit, restricted interests, and repetitive behavior. Several studies suggested a link between autism and the dysregulation of the Wnt signaling pathway which is mainly involved in cell fate determination, cell migration, cell polarity, neural patterning, and organogenesis. Despite the absence of effective therapy, significant progress has been made in understanding the pathogenesis of ASD. Neuropharmacological studies showed that drugs acting on the Wnt pathway like Canagliflozin can alleviate autistic-like behavior in animal models. Hence, this pathway could potentially be a futuristic therapeutic target to mitigate autism’s symptoms. This systematic review aims to collect and analyze evidence that elucidates how alterations in the Wnt pathway may contribute to the pathogenesis of autism in animal models at the molecular, cellular, and physiological levels. Comprehensive searches were conducted across multiple databases, including PubMed, Web of Science, Embase, and Scopus to identify relevant studies up to March 2024. The inclusion criteria encompassed experimental studies that focused on the link between autism and this pathway, and the quality assessment was ensured by SYRCLE’s risk of bias tools. Collectively, the included articles highlighted the possible implication of this pathway in the abnormalities found in autism, which impacted processes such as energy metabolism, oxidative stress, and neurogenesis. These alterations could underlie autistic behavior by affecting synaptic transmission and mitochondrial function.

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5. Cannon M, Toma R, Ganeshan S, de Jesus Alvarez Varela E, Vuyisich M, Banavar G. Salivary Transcriptome and Mitochondrial Analysis of Autism Spectrum Disorder Children Compared to Healthy Controls. NeuroSci;2024 (Sep);5(3):276-290.

Autism rates have been reported to be increasing rapidly in industrialized societies. The pathology most often combines neurological symptoms associated with language and social impairments with gastrointestinal symptoms. This study aimed to measure differences in oral metatranscriptome and mitochondrial health between ASD children and neurotypical USA and Colombia (« Blue Zone ») children. In addition, this study aimed to determine whether using prebiotics and probiotics would change the oral microbiome and mitochondrial health of ASD children. Buccal swabs and saliva samples were obtained from 30 autistic individuals (USA) at three intervals: prior to intervention, post-prebiotic, and post-probiotic. In addition, a subject component who were neurotypical, which included individuals from the USA (30) and Colombia (30), had buccal swabbing and salivary sampling performed for metatranscriptomic and mitochondrial comparison. Significant differences were observed in the temporal data, demonstrating shifts that interventions with probiotics and polyols may have precipitated. Particular bacterial strains were significantly more prevalent in the autism group, including a strain that reduced neurotransmitter levels via enzymatic degradation. This supports the hypothesis that the microbiome may influence the occurrence and degree of autism. Verbal skills increased in six of the 30 ASD subjects following xylitol and three more after probiotic supplementation, according to both parental reports and the subjects’ healthcare providers.

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6. Chen T, Jiang J, Xu M, Dai Y, Gao X, Jiang C. Atypical prefrontal neural activity during an emotional interference control task in adolescents with autism spectrum disorder: A functional near-infrared spectroscopy study. Neuroimage;2024 (Oct 26):120907.

Autism spectrum disorder (ASD) is typically characterized by impairments in social interaction and communication, which may be associated with a failure to naturally orient to social stimuli, particularly in recognizing and responding to facial emotions. As most previous studies have used nonsocial stimuli to investigate inhibitory control in children and adults with ASD, little is known about the behavioral and neural activation patterns of emotional inhibitory control in adolescent with ASD. Functional neuroimaging studies have underscored the key role of the prefrontal cortex (PFC) in inhibitory control and emotional face processing. Thus, this study aimed to examine whether adolescent with ASD exhibited altered PFC processing during an emotional Flanker task by using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-one adolescents with high-functioning ASD and 26 typically developing (TD) adolescents aged 13-16 years were recruited. All participants underwent an emotional Flanker task, which required to decide whether the centrally positioned facial emotion is consistent with the laterally positioned facial emotion. TD adolescents exhibited larger RT and mean O(2)Hb level in the incongruent condition than the congruent condition, evoking cortical activations primarily in right PFC regions in response to the emotional Flanker effect. In contrast, ASD adolescents failed to exhibit the processing advantage for congruent versus incongruent emotional face in terms of RT, but showed cortical activations primarily in left PFC regions in response to the emotional Flanker effect. These findings suggest that adolescents with ASD rely on different neural strategies to mobilize PFC neural resources to address the difficulties they experience when inhibiting the emotional face.

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7. Chen Y, Yang C, Gao B, Chen K, Jao Keehn RJ, Müller RA, Yuan LX, You Y. Altered functional connectivity of unimodal sensory and multisensory integration networks is related to symptom severity in autism spectrum disorders. Biol Psychiatry Cogn Neurosci Neuroimaging;2024 (Nov 2)

BACKGROUND: Atypical sensory processing is a prevalent feature in autism spectrum disorders (ASD) and constitutes a core diagnostic criterion in the Diagnostic and Statistical Manual of Mental of Disorders, 5th edition (DSM-5). However, neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear. METHODS: This study examined intrinsic functional connectivity (FC) patterns among five unimodal sensory and multisensory integration (MSI) networks in ASD with a large multi-site dataset (n = 646), and investigated the relationships among altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms with correlation and mediation analyses. RESULTS: Relative to typically developing (TD) controls, the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI-unimodal-sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits. CONCLUSIONS: ASD-specific olfactory overconnectivity and MSI-unimodal-sensory underconnectivity lend support to the Intense World Theory and Weak Central Coherence Theory, suggesting olfactory hypersensitivity at the expense of multisensory integration as potential neural mechanisms underlying atypical sensory processing in ASD. These atypical FC patterns further suggest potential targets for psychological and neuromodulatory interventions.

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8. Coppola S, Nocerino R, Oglio F, Golia P, Falco MC, Riccio MP, Carucci L, Rea T, Simeone S, Garotti R, Marani N, Bravaccio C, Canani RB. Adverse food reactions and alterations in nutritional status in children with autism spectrum disorders: results of the NAFRA project. Ital J Pediatr;2024 (Nov 4);50(1):228.

BACKGROUND: To assess the adverse food reactions (AFR) prevalence in children with autism spectrum disorder (ASD) and in non-ASD healthy controls (NASD). Nutritional status alterations, food selectivity and adherence to Mediterranean Diet (MD) were also evaluated. METHODS: The NAFRA (Nutritional status and Adverse Food Reactions in children with Autism Spectrum Disorder) project was an observational, case-control, comparative study conducted at a tertriary center for pediatrics involving Caucasian patients of both sexes, aged 18 months-7 years, with a diagnosis of ASD, and matched NASD controls. RESULTS: From October 2017 to December 2023, 100 ASD patients [79 male, mean (± SD) age 49.9 months (± 15.4)] and 100 NASD controls [75 male, mean (± SD) age 49.8 months (± 17.7)] were enrolled at the Pediatric Section of the Department of Translational Medical Science of the University of Naples Federico II. A significantly higher prevalence of AFR was observed in ASD patients if compared with NASD (16% vs. 2%, p = 0.001), mainly due to a higher prevalence of food allergy (7% vs. 1%, p = 0.03). A significantly higher prevalence of food intolerance and celiac disease was also observed in ASD children. The rate of obesity was significantly higher in ASD patients compared to NASD. Food selectivity and low MD-adherence were more frequent in ASD children (26% vs. 2%, p < 0.0001 and 28% vs. 16%, p = 0.041, respectively). CONCLUSIONS: The high rate of AFR, obesity and unhealthy dietary habits observed in ASD children strongly suggest the importance of a multidisciplinary approach, providing early diagnosis of AFR and appropriate nutritional management to improve core and associated ASD-related conditions. TRIAL REGISTRATION: The NAFRA Project was registered on https://clinicaltrials.gov/ with the identifier NCT04719923. Registered 18 January 2021. https://clinicaltrials.gov/study/NCT04719923 .

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9. Fadda R, Congiu S, Doneddu G, Carta M, Piras F, Gabbatore I, Bosco FM. Th.o.m.a.s.: new insights into theory of mind in adolescents with autism spectrum disorder. Front Psychol;2024;15:1461980.

Previous studies indicated atypical Theory of Mind (ToM) abilities in individuals with autism spectrum disorder (ASD) at different ages. However, research focused on adolescents with ASD is still rare. This study aims to fill the gaps in the literature, by investigating ToM abilities in adolescents with ASD and in a group of typically developing ones. We applied the Theory of Mind Assessment Scale (Th.o.m.a.s.), a semi-structured interview that allows a multi-dimensional measurement of ToM, including different perspectives (first/s-order, first/third-person, egocentric/allocentric), various mental states (emotions, desires, beliefs) and metacognitive abilities related with mental states (awareness, relation, and strategies). The results indicated that ToM develops atypically in ASD, with strengths and weaknesses. First, participants with ASD were comparable to controls in some specific ToM aspects, i.e., third-person ToM, both from an egocentric and an allocentric perspective. However, they were significantly weaker in attributing an understanding of the mental states of others, both in first- and second-order ToM scenarios. Second, they showed the same level of awareness about mental states as controls, but they were significantly weaker in conceptualizing the relationship between mental states and behavior. Also, they found it very difficult to think about possible strategies that they or others might employ to realize desires and needs. Finally, they performed similarly to controls in understanding emotions, while they poorly understood desires and beliefs. These results point out the distinctive characteristics of ToM development in individuals with ASD, with important implications for individualized interventions.

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10. Fan L, Li Q, Shi Y, Li X, Liu Y, Chen J, Sun Y, Chen A, Yang Y, Zhang X, Wang J, Wu L. Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder. BMC Med;2024 (Nov 4);22(1):504.

BACKGROUND: Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. METHODS: The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. RESULTS: Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. CONCLUSIONS: S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

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11. Frazier TW, Chetcuti L, Uljarevic M. Evidence That Intervention Dosage Is Associated With Better Outcomes in Autism. JAMA Pediatr;2024 (Nov 4)

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12. Hnoonual A, Kaewfai S, Limwongse C, Limprasert P. Prevalence and implications of fragile X premutation screening in Thailand. Sci Rep;2024 (Nov 1);14(1):26257.

The fragile X premutation is a public health concern worldwide. Implementing a comprehensive screening program for FMR1 premutation alleles could empower individuals and families with information, supporting informed health decisions and potentially reducing the incidence of fragile X syndrome (FXS). This study aimed to determine the prevalence of FMR1 premutations in the Thai population. We screened 369 female blood donors and 449 males with tremor and/or ataxia who tested negative for spinocerebellar ataxia (SCA) types 1, 2, and 3 for FMR1 CGG repeat expansions. Among the female blood donors, 0.27% (1/369) had a premutation allele, and 1.08% (4/369) had intermediate alleles. One female with a premutation carrier had 89 CGG repeats with one AGG interruption. In the male cohort, no premutations or full mutations were found; however, intermediate alleles were identified in 0.67% (3/449) of the males. This study provides the evidence of fragile X premutation screening in the Thai population. These findings contribute to the understanding of FMR1 premutation prevalence in Thailand and should encourage wider discussions on the feasibility for a national fragile X carrier screening program in Thailand to reduce the burden of fragile X-associated disorders.

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13. Houben F, den Heijer CD, Dukers-Muijrers NH, Nava JB, Theunissen M, van Eck B, Smeets-Peels C, Hoebe CJ. Self-reported compliance with infection prevention and control of healthcare workers in Dutch residential care facilities for people with intellectual and developmental disabilities during the COVID-19 pandemic: A cross-sectional study. Disabil Health J;2023 (Oct 11):101542.

BACKGROUND: Compliance of healthcare workers (HCWs) with infection prevention and control (IPC) is crucial to resident safety. Nevertheless, HCWs’ compliance with IPC has not been previously studied in a disability care setting. OBJECTIVE: To assess levels of self-reported compliance with IPC among HCWs in residential care facilities (RCFs) for people with intellectual and developmental disabilities (IDDs), and to assess whether IPC compliance varies among different professional groups. METHODS: A total of 285 HCWs from 16 Dutch RCFs completed an online questionnaire assessing 16 IPC procedures, following national guidelines. Data were analysed using descriptive statistics and chi-square tests to assess potential differences in compliance between professional groups. RESULTS: Overall, HCWs complied on average with 68.7% of IPC. Only 30.1% of HCWs had sufficient compliance (defined as compliance with ≥80% of IPC practices). Compliance varied considerably between individual IPC procedures, in which compliance with wearing short-sleeved clothes (30.9%) and using disposable protective clothing (32.7%) were the lowest. Compliance with jewellery and hair regulations was suboptimal (45.6% and 55.4%, respectively). Non-medical professionals complied with IPC less frequently (social workers, 24.2%; behavioural specialists, 12.9%) than medical professionals (47.4%) (p < 0.001). CONCLUSIONS: The majority of HCWs had suboptimal compliance with IPC. As IPC compliance differs between professionals, recommendations are to 1) implement tailored education and training programmes, and 2) pursue a facility-wide minimum required IPC compliance. Implementing and communicating a minimum set of IPC procedures - including hand hygiene, personal hygiene, and clothing requirements - applying to all professionals is important to minimise the infection transmission risk in RCFs for people with IDDs.

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14. 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 (Nov 4);33(6):3051-3068.

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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15. LaPoint SC, Simmons GL, Heinly J, Delgado D, Shepherd WS, Brookman-Frazee L, Storch EA, Maddox BB. « Education would be step number one »: Community mental health clinicians’ training and support needs to treat anxiety in autistic youth. Res Autism Spectr Disord;2024 (Sep);117

BACKGROUND: Autistic youth experience high rates of anxiety, which has been treated with modified cognitive-behavioral therapy (CBT), often integrating exposure therapy. Such anxiety treatments are effective for this population; however, there remains a gap between these evidence-based mental health interventions and their implementation in community mental health (CMH) services where autistic youth receive care. METHOD: This qualitative study conducted semi-structured interviews with four types of community members in the United States: 15 autistic youth with anxiety, 15 caregivers of autistic youth with anxiety, 11 CMH clinicians, and 8 CMH clinic leaders. Participants identified the training needs of CMH clinicians to support the delivery of CBT for autistic youth with anxiety. RESULTS: Through inductive thematic analysis, three themes were found: presentation of autism and anxiety, intervention delivery, and training format. Participants highlighted the need for clinician education to understand the varying presentations of autism and co-occurring anxiety and how to effectively deliver a personalized mental health intervention for autistic youth. Clinicians also desired a clinician training program that includes engaging components and offers individualized, ongoing support while the intervention is delivered. CONCLUSIONS: Findings from this study will inform the development of a clinician training program to deliver CBT modified for autistic youth with anxiety in CMH contexts.

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16. Lin PI, Wu WT, Guo YL. Screen Time Before 2 Years of Age and Risk of Autism at 12 Years of Age. JAMA Pediatr;2024 (Nov 4)

This cohort study evaluates the association between screen time and autism spectrum disorder by considering socioeconomic factors as instrumental variables. eng

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17. Lin S, Su X, Cao D. Current research status and progress in neuropsychological development of children with congenital heart disease: A review. Medicine (Baltimore);2024 (Nov 1);103(44):e40489.

Children with congenital heart disease (CHD) are receiving widespread attention for their neuropsychological developmental issues, which include cognitive, adaptive, motor, speech, behavioral, and executive functioning deficits as well as autism spectrum disorders. Timely identification of risk factors influencing neuropsychological development and implementation of appropriate interventions are crucial for enhancing the neuropsychological outcomes of children with CHD, ultimately benefiting the children, their families, and society as a whole. This comprehensive review article aimed to explore the epidemiology, risk factors, assessment methods, and monitoring strategies of neuropsychological development in children with CHD. By providing a detailed examination of these factors, this review serves as a valuable resource for researchers and practitioners in the field, facilitating deeper understanding and more effective management of neuropsychological issues in this vulnerable population.

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18. Lundqvist LO, Sjödin L, Karvonen E, Arnell S. Evaluating the impact of needs assessment models on autistic children’s participation in the habilitation process: protocol for a prospective observational study. BMJ Open;2024 (Nov 1);14(10):e089135.

INTRODUCTION: The rising prevalence of autism spectrum disorder (ASD) among children poses significant challenges for healthcare services. Research has underscored the crucial role of children’s involvement in their healthcare. However, due to the intricate nature of ASD, marked by communication and social interaction differences, healthcare providers face challenges in tailoring their services to accommodate these children. This project aims to explore the impact of two distinct needs assessment models on children’s participation in the needs assessment process. METHODS AND ANALYSIS: We will conduct a prospective observational study comparing responses from children subjected to two different needs assessment procedures: survey-based and meeting-based. Supplementary data will be collected from the children’s parents/guardians and healthcare professionals. Data collection methods will include questionnaires, interviews and document analysis of individual habilitation plans. We aim to recruit 120 children aged 7-17 diagnosed with ASD but without intellectual disability, with 60 undergoing the survey-based needs assessment and 60 undergoing the meeting-based assessment. The primary outcome measure will be the perception of participation in the needs assessment procedure. Secondary outcomes will include the children’s quality of life and mental health; the parents’ knowledge of their child’s strengths, abilities and special needs; and the parents’ perception of the quality of collaboration with the healthcare team. ETHICS AND DISSEMINATION: The study received ethics approval from the Swedish Ethical Review Authority on 4 March 2024 (reference number 2024-00227-01). All children and their caregivers will receive both verbal and written information about the study before being asked to provide written informed consent to participate. The findings will be disseminated through publication in peer-reviewed journals and presentation at conferences. Additionally, a popular science report summarising the data and its interpretation will be published. TRIAL REGISTRATION NUMBER: NCT06381856.

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19. Mangnus M, Koch SBJ, Cai K, Romaneli MG, Hagoort P, Bašnáková J, Stolk A. Preserved Spontaneous Mentalizing amid Reduced Intersubject Variability in Autism during a Movie Narrative. Biol Psychiatry Cogn Neurosci Neuroimaging;2024 (Oct 26)

BACKGROUND: While individuals with autism often face challenges in everyday social interactions, they may demonstrate proficiency in structured Theory of Mind (ToM) tasks that assess their ability to infer others’ mental states. Using functional MRI and pupillometry, we investigated whether these discrepancies stem from diminished spontaneous mentalizing or broader difficulties in unstructured contexts. METHODS: Fifty-two adults diagnosed with autism and 52 neurotypical controls viewed ‘Partly Cloudy’, a nonverbal animated film with a dynamic social narrative known to engage the ToM brain network during specific scenes. Analysis focused on comparing brain and pupil responses to these ToM events. Additionally, dynamic intersubject correlations explored the variability of these responses throughout the film. RESULTS: Both groups showed similar brain and pupil responses to ToM events and provided comparable descriptions of the characters’ mental states. However, participants with autism exhibited significantly stronger correlations in their responses across the film’s social narrative, indicating reduced inter-individual variability. This distinct pattern emerged well before any ToM events and involved brain regions beyond the ToM network. CONCLUSIONS: Our findings provide functional evidence of spontaneous mentalizing in autism, demonstrating this capacity in a context affording but not requiring mentalizing. Rather than responses to ToM events, a novel neurocognitive signature – inter-individual variability in brain and pupil responses to evolving social narratives – differentiated neurotypical individuals from those with autism. These results suggest that idiosyncratic narrative processing in unstructured settings, a common element of everyday social interactions, may offer a more sensitive scenario for understanding the autistic mind.

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20. Mansour Y, Kulesza R. Obliteration of a glycinergic projection to the medial geniculate in an animal model of autism. Front Cell Neurosci;2024;18:1465255.

Auditory dysfunction affects the vast majority of people with autism spectrum disorder (ASD) and can range from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid (VPA) is associated with significant risk of an ASD diagnosis in humans and timed in utero exposure to VPA is utilized as an animal model of ASD. VPA-exposed rats have significantly fewer neurons in their auditory brainstem, thalamus and cortex, reduced ascending projections to the midbrain and thalamus and reduced descending projections from the cortex to the auditory midbrain. Consistent with these anatomical changes, VPA-exposed animals also have abnormal auditory brainstem responses. We have recently described a significant ascending projection from calbindin-positive neurons in the medial nucleus of the trapezoid body (MNTB) to the ventral division of the medial geniculate (vMG) in rats that bypasses the central nucleus of the inferior colliculus (CNIC). Since we found that axonal projections to the vMG in VPA-exposed rats are reduced beyond what is predicted from neuron loss alone, we hypothesize that VPA exposure would result in a significant reduction in the MNTB projection to the vMG. We examined this hypothesis by quantifying the proportion of retrogradely-labeled neurons in the MNTB of control and VPA-exposed animals after injections of retrograde tracers in the CNIC and vMG in control and VPA-exposed animals. Our results indicate that in control animals, the MNTB forms the largest projection from the superior olivary complex to the MG and that this projection is nearly abolished by in utero VPA exposure.

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21. Meehan RR, Pennings S. Rett syndrome: interferon-γ to the rescue?. EMBO Mol Med;2024 (Nov 4)

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22. Mo S, Bu F, Bao S, Yu Z. Comparison of effects of interventions to promote the mental health of parents of children with autism: A systematic review and network meta-analysis. Clin Psychol Rev;2024 (Oct 29);114:102508.

Individuals diagnosed with autism spectrum disorders often face persistent challenges in social interaction and engage in repetitive and stereotyped behaviors. Parenting a child with autism can profoundly affect parents both physically and psychologically, potentially leading to negative impacts on their mental health. This study employs a network meta-analysis methodology to evaluate the comparative effectiveness of mental health interventions specifically designed for parents of autistic children. A total of 69 empirical intervention studies involving 4213 parents of autistic children were included in the analysis. Employing the frequency framework model and utilizing Stata 16.0 software, we quantitatively analyzed the impact of various interventions on anxiety, depression, parenting stress, and parenting self-efficacy. Our findings indicate that mindfulness-based interventions demonstrate the highest efficacy in reducing parenting stress, while cognitive behavioral therapy is effective in alleviating anxiety and depression in parents of children with autism. Psychoeducational interventions have shown significant benefits in mitigating parental anxiety, depression, and parenting stress, and acceptance and commitment (ACT) displays promising outcomes in reducing depression. We also elaborate on the underlying mechanisms that contribute to the effectiveness of these interventions. This network meta-analysis presents valuable insights for the development of targeted interventions to provide support to parents of children with autism.

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23. Nakamura T, Nagayama H, Sasada S. Development and Validation of the Participation Questionnaire for Preschoolers with Autism Spectrum Disorder: Structural Validity, Internal Consistency, and Construct Validity. Phys Occup Ther Pediatr;2024 (Nov 3):1-16.

AIM: This study aimed to develop the Participation Questionnaire for Preschoolers (PQP) and validate its psychometric properties as a disability-specific tool designed to assess participation in preschool-aged children with autism spectrum disorder (ASD). METHODS: This cross-sectional study recruited caregivers of 412 children, including those diagnosed with ASD and those at risk for neurodevelopmental disorders. Participants were recruited from child development facilities, medical institutions, and developmental support websites across Japan. Data from 287 children diagnosed with ASD were analyzed for item reduction, followed by exploratory factor analysis and the calculation of Cronbach’s alpha to evaluate internal consistency. Five hypotheses were tested to assess construct validity. RESULTS: Item reduction resulted in the removal of seven items and the identification of four factors: Friendship and Education, Family Satisfaction, Daily Living and Independence, and Leisure and Community Life. Cronbach’s alpha values for these factors ranged from 0.74 to 0.88, indicating acceptable internal consistency. Three of the five hypotheses related to construct validity were supported, aligning with expectations. CONCLUSION: The PQP exhibited structural validity, internal consistency, and construct validity. However, further longitudinal studies are needed to validate its measurement properties over time.

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24. Ohmoto Y, Terada K, Shimizu H, Kawahara H, Iwanaga R, Kumazaki H. Machine learning’s effectiveness in evaluating movement in one-legged standing test for predicting high autistic trait. Front Psychiatry;2024;15:1464285.

INTRODUCTION: Research supporting the presence of diverse motor impairments, including impaired balance coordination, in children with autism spectrum disorder (ASD) is increasing. The one-legged standing test (OLST) is a popular test of balance. Since machine learning is a powerful technique for learning predictive models from movement data, it can objectively evaluate the processes involved in OLST. This study assesses machine learning’s effectiveness in evaluating movement in OLST for predicting high autistic trait. METHODS: In this study, 64 boys and 62 girls participated. The participants were instructed to stand on one leg on a pressure sensor while facing the experimenter. The data collected in the experiment were time-series data pertaining to pressure distribution on the sole of the foot and full-body images. A model to identify the participants belonging to High autistic trait group and Low autistic trait group was developed using a support vector machine (SVM) algorithm with 16 explanatory variables. Further, classification models were built for the conventional, proposed, and combined explanatory variable categories. The probabilities of High autistic trait group were calculated using the SVM model. RESULTS: For proposed and combined variables, the accuracy, sensitivity, and specificity scores were 1.000. The variables shoulder, hip, and trunk are important since they explain the balance status of children with high autistic trait. Further, the total Social Responsiveness Scale score positively correlated with the probability of High autistic trait group in each category of explanatory variables. DISCUSSION: Results indicate the effectiveness of evaluating movement in OLST by using movies and machine learning for predicting high autistic trait. In addition, they emphasize the significance of specifically focusing on shoulder and waist movements, which facilitate the efficient predicting high autistic trait. Finally, studies incorporating a broader range of balance cues are necessary to comprehensively determine the effectiveness of utilizing balance ability in predicting high autistic trait.

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25. Pecukonis M, Butler LK, Tager-Flusberg H. What role does the environment play in language development? Exploring the associations among socioeconomic status, parent language input, and language skills in school-aged children with autism. Autism Res;2024 (Nov 4)

Language development in children with autism is influenced by proximal (e.g., parent language input) and distal (e.g., socioeconomic status) environmental constructs. Studies have found that « rich and responsive » parent language input supports autistic children’s language development, and recent work has reported positive associations between measures of socioeconomic status (SES) and child language skills. However, little is known about how these proximal and distal environmental constructs interact to shape language development in autism. In a sample of 74 autistic school-aged children, the present study investigated the associations among measures of SES, the quantity and quality of language produced by parents and children during home-based dyadic parent-child interactions, and children’s expressive and receptive language skills. Results showed that annual household income was positively associated with parent number of total words (NTW), parent number of different words (NDW), and parent mean length of utterance (MLU), while neither parent education level nor annual household income were significantly associated with measures of child language skills. Parent MLU was positively associated with child MLU and child expressive language skills. Findings suggest that annual household income may influence both the quantity and quality of parent language input, and that parent MLU, a qualitative measure of parent language input, may play a particularly important role in shaping autistic children’s expressive language development. Future research should study longitudinal associations among SES, parent language input, and child language skills, as identifying environmental predictors of language skills in autism may facilitate the creation of more effective interventions that support language development.

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26. Persico AM, Asta L, Chehbani F, Mirabelli S, Parlatini V, Cortese S, Arango C, Vitiello B. The pediatric psychopharmacology of autism spectrum disorder: A systematic review part II: The future. Prog Neuropsychopharmacol Biol Psychiatry;2024 (Oct 26):111176.

Part I of this systematic review summarized the state-of-the-art of pediatric psychopharmacology for Autism Spectrum Disorder (ASD), a severe and lifelong neurodevelopmental disorder. The purpose of this Part II follow-up article is to provide a systematic overview of the experimental psychopharmacology of ASD. To this aim, we have first identified in the Clinicaltrials.gov website all the 157 pharmacological and nutraceutical compounds which have been experimentally tested in children and adolescents with ASD using the randomized placebo-controlled trial (RCT) design. After excluding 24 drugs already presented in Part I, a systematic review spanning each of the remaining 133 compounds was registered on Prospero (ID: CRD42023476555), performed on PubMed (August 8, 2024), and completed with EBSCO, PsycINFO (psychology and psychiatry literature) and the Cochrane Database of Systematic reviews, yielding a total of 115 published RCTs, including 57 trials for 23 pharmacological compounds and 48 trials for 17 nutraceuticals/supplements. Melatonin and oxytocin were not included, because recent systematic reviews have been already published for both these compounds. RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation. For the vast majority of compounds, including cannabidiol, vasopressin, and probiotics, insufficient evidence of efficacy and safety is available. However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize « drug-based » information, which will be ultimately merged to provide clinicians with a « symptom-based » consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials.

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27. Prahl A. The Effects of Functional Reading Activities to Motivate and Empower for Autistic Young Adults: A Single-Case Design Study. Am J Speech Lang Pathol;2024 (Nov 4);33(6):2805-2822.

PURPOSE: The purpose of this study was to examine the effects of Functional Reading Activities to Motivate and Empower (FRAME) on use of reading comprehension strategies in intellectually and/or developmentally disabled young adults. METHOD: A single-case, multiple-probe design across functional literacy stimuli (e.g., text messages, e-mails) was replicated across three intellectually or developmentally disabled 23- to 26-year-old young adults, all of whom had a primary diagnosis of autism. Within FRAME, reading comprehension strategies were taught and practiced within the context of functional texts or activities of daily living that involve written language (e.g., text messages, e-mails). Each session followed the teach-model-coach-review approach and was conducted via telepractice. Participants’ use of reading comprehension strategies was measured in baseline, intervention, maintenance, and with generalization probes. RESULTS: Visual analysis of the data indicated a functional relation between FRAME and the use of reading comprehension strategies for two of the three autistic young adults. All participants maintained increased use of reading comprehension strategies post-intervention. CONCLUSIONS: This study provides preliminary evidence that FRAME is associated with improved use of reading comprehension strategies that maintains over time. Thus, FRAME has the potential to support continued improvement of functional reading skills throughout the lifespan, which is critical as autistic individuals make the transition from adolescence to adult life. Further research is needed to evaluate the effects of the intervention on more distal outcomes of written language and to examine how to best tailor the intervention to individual differences to optimize outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.26882422.

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28. Protic D, Breeze E, Mendoza G, Zafarullah M, Abbeduto L, Hagerman R, Coffey C, Cudkowicz M, Durbin-Johnson B, Ashwood P, Berry-Kravis E, Erickson CA, Filipink R, Gropman A, Lehwald L, Maxwell-Horn A, Morris S, Bennett AP, Prock L, Talboy A, Tartaglia N, Veenstra-VanderWeele J, Tassone F. Negative effect of treatment with mGluR5 negative allosteric modulator AFQ056 on blood biomarkers in young individuals with Fragile X syndrome. SAGE Open Med;2024;12:20503121241282401.

BACKGROUND: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show a significant impact of AFQ056 on language development in children with fragile X syndrome aged 3-6 years. OBJECTIVES: The current analyses from biospecimens collected in the FXLEARN study aimed to determine whether AFQ056 affects the level of potential biomarkers associated with Akt/mTOR and matrix metalloproteinase 9 signaling in young individuals with fragile X syndrome. Previous research has indicated that these biomarkers play crucial roles in the pathophysiology of fragile X syndrome. DESIGN: A double-blind placebo-controlled parallel-group flexible-dose forced titration design. METHODS: Blood samples for biomarkers were collected during the FXLEARN at baseline and subsequent visits (1- and 8-month visits). Biomarker analyses included fragile X messenger ribonucleoprotein-1 genotyping by Southern blot and PCR approaches, fragile X messenger ribonucleoprotein-1 mRNA levels determined by PCR, matrix metalloproteinase 9 levels’ detection using a magnetic bead panel, and targets of the Akt/mTOR signaling pathway with their phosphorylation levels detected. RESULTS: This research revealed that administering AFQ056 does not affect the expression levels of the investigated blood biomarkers in young children with fragile X syndrome. CONCLUSION: Our findings of the lack of association between clinical improvement and biomarkers’ levels in the treatment group are in line with the lack of benefit observed in the FXLEARN study. These findings indicate that AFQ056 does not provide benefits as assessed by primary or secondary endpoints. REGISTRATION: ClincalTrials.gov NCT02920892.

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29. Sandbank M, Pustejovsky JE. Evidence That Intervention Dosage Is Associated With Better Outcomes in Autism-Reply. JAMA Pediatr;2024 (Nov 4)

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30. Sun B, Xu Y, Kat S, Sun A, Yin T, Zhao L, Su X, Chen J, Wang H, Gong X, Liu Q, Han G, Peng S, Li X, Liu J. Exploring the most discriminative brain structural abnormalities in ASD with multi-stage progressive feature refinement approach. Front Psychiatry;2024;15:1463654.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by increasing prevalence, diverse impairments, and unclear origins and mechanisms. To gain a better grasp of the origins of ASD, it is essential to identify the most distinctive structural brain abnormalities in individuals with ASD. METHODS: A Multi-Stage Progressive Feature Refinement Approach was employed to identify the most pivotal structural magnetic resonance imaging (MRI) features that distinguish individuals with ASD from typically developing (TD) individuals. The study included 175 individuals with ASD and 69 TD individuals, all aged between 7 and 18 years, matched in terms of age and gender. Both cortical and subcortical features were integrated, with a particular focus on hippocampal subfields. RESULTS: Out of 317 features, 9 had the most significant impact on distinguishing ASD from TD individuals. These structural features, which include a specific hippocampal subfield, are closely related to the brain areas associated with the reward system. CONCLUSION: Structural irregularities in the reward system may play a crucial role in the pathophysiology of ASD, and specific hippocampal subfields may also contribute uniquely, warranting further investigation.

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31. Tromans S, Sawhney I, Shankar R. The potential unintended consequences of Mental Health Act reforms in England and Wales on people with intellectual disability and/or autism: commentary, author response, Tromans et al. Br J Psychiatry;2024 (Sep);225(3):414-415.

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32. Yurumez E, Temelturk RD, Kaymak B, Karabıyıkoğlu Y, Zengin ND. Catatonia in autism spectrum disorders: Prevalence, functional impact, and diagnostic insights. Psychiatry Res;2024 (Oct 28);342:116250.

The current study aimed to evaluate subtle catatonia behaviors and functionality in adolescents with autism spectrum disorders (ASD). The sample consisted of 48 patients (11 female, 37 male) aged 12-18 (13.77 ± 2.01). DSM-5 catatonia criteria and Bush-Francis Catatonia Rating Scale (BCRS) was utilized to assess catatonia, while the impairment in functionality was appraised using the Global Assessment Scale. Parents fulfilled the Revised Child Anxiety and Depression Scale-Parent version (RCADS-PV) and Repetitive Behavior Scale-Revised (RBS-R). The presence of catatonia was detected in 18 out of 48 (37.5 %) participants according to BCRS, and in 16 cases (35.4 %) according to DSM-5 criteria. A significant association between two diagnostic tools was observed (p < 0.001). In the group with mild impairment in functionality, 2 cases had catatonia (12.5 %), while in the group with more impaired functionality, 16 cases (50 %) had catatonia (p = 0.011) according to BCRS. Major depressive disorder subscale scores of RCADS-PV and stereotypic movements (RBS-R) were correlated with the presence of catatonia (p < 0.05). The findings suggest a higher prevalence of catatonia in ASD, and a potential correlation between the presence of catatonia and functionality. More research is warranted to highlight the presence and course of catatonia beginning from the early years of ASD.

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33. Zhou P, Peng S, Wen S, Lan Q, Zhuang Y, Li X, Shi M, Zhang C. The Cerebellum-Ventral Tegmental Area Microcircuit and Its Implications for Autism Spectrum Disorder: A Narrative Review. Neuropsychiatr Dis Treat;2024;20:2039-2048.

The cerebellum has long been implicated in the etiopathogenesis of autism spectrum disorder (ASD), and emerging evidence suggests a significant contribution by reciprocal neural circuits between the cerebellum and ventral tegmental area (VTA) in symptom expression. This review provides a concise overview of morphological and functional alterations in the cerebellum and VTA associated with ASD symptoms, primarily focusing on human studies while also integrating mechanistic insights from animal models. We propose that cerebello-VTA circuit dysfunctional is a major contributor to ASD symptoms and that these circuits are promising targets for drugs and therapeutic brain stimulation methods.

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