1. Abualait T, Alabbad M, Kaleem I, Imran H, Khan H, Kiyani MM, Bashir S. Autism Spectrum Disorder in Children: Early Signs and Therapeutic Interventions. Children (Basel). 2024; 11(11).

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in communication, social interaction difficulties, and repetitive behaviors that can hinder a child’s development. The growing prevalence of autism necessitates early detection and effective intervention strategies. This review summarizes the current knowledge of early indicators of ASD, including brain development markers and behavioral signs visible in infants. It investigates diagnostic processes, emphasizing the importance of timely detection at 18 to 24 months using established screening tools. We discuss a variety of therapeutic approaches, including behavioral interventions, educational strategies such as music therapy, and technological advancements such as speech-generating devices. Furthermore, we investigate pharmacological options for treating associated symptoms, emphasizing the lack of targeted medications for core ASD symptoms. Finally, we present evidence highlighting the positive effects of early intervention on developmental outcomes, advocating for individualized treatment plans to enhance the well-being of children with ASD. This comprehensive overview aims to inform ongoing ASD research and clinical practices.

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2. Al Fahdawi Z, Dissanayake C, Abdullahi I. Developmental and Functional Outcomes Amongst Culturally and Linguistically Diverse Autistic Children. J Autism Dev Disord. 2024.

Children typically learn by attending to other people. Autism traits may impact access to social stimuli fundamental to early learning, increasing children’s likelihood of a learning disability. Recent reports have highlighted that Autistic children from minority backgrounds have a higher likelihood of co-occurring intellectual disability. This study aimed to firstly confirm that early autism traits are concurrently and prospectively associated with lower developmental quotients, and secondly to examine the developmental and functional gains in Culturally and Linguistically Diverse (CALD) and non-CALD Autistic children following one year of Group-based Early Start Denver Model (G-ESDM). Secondary data on 114 non-CALD and 91 CALD Autistic preschoolers receiving the G-ESDM was utilised to address the study aims. Children were administered the Autism Diagnostic Observation Schedule (ADOS) at entry into the service. The Mullen Scales of Early Learning and the Vineland Adaptive Behaviour Scales-II were administered at both entry (Time 1) and 12 months later (Time 2). While no concurrent associations were found between autism traits and Developmental Quotient (DQ), significant associations were found prospectively with ADOS scores at Time 1 and DQ at Time 2, holding for both groups after controlling for DQ at Time 1. Autistic children made significant gains in cognition and functional behaviour following one year of early therapy, with no differences between the two groups. The results indicate that young Autistic children make significant gains in early development and add to the sparse research on the developmental and functional outcomes of Autistic children from CALD communities.

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3. Alegría PL, Landim SF, Pérez Valdés VA, Martínez Escudero N, Botelho JN, Branco BHM, Villagrán F, Sandoval C, Marques DCS, Parrón Carreño T, González MM. Parental Stress in Autistic Children with Poor Oral Hygiene: A Pilot Study to Develop and Validate a Measurement Scale. Healthcare (Basel). 2024; 12(22).

Background/Objectives: Research indicates that children with autism spectrum disorder (ASD) exhibit a deficiency in skills and initiative when it comes to adhering to daily oral hygiene routines. This, in turn, increases the likelihood of oral pathologies, thereby placing a significant emotional strain on their parents. In addition to the typical stress they already experience, parents of children with ASD are also burdened with pediatric oral health issues. However, a review of the literature reveals a lack of studies measuring stress in parents of children whose oral health affects their autistic condition. This research aimed to design and to validate a stress scale for parents of autistic children with poor oral hygiene. Methods: The study used an exploratory, non-experimental design to validate and determine the reliability of the scale. Scale reliability was assessed through a cross-sectional pilot test to evaluate internal scale consistency, with a focus on item similarity. We used Aiken’s V to estimate the validity of the scale, and Cronbach’s α for calculating scale reliability. Calculations, estimations, and statistical analysis were conducted using SPSS. Results: Expert validation, a pilot test, and a cross-sectional, non-experimental design established the reliability of the scale. Conclusions: We conclude that the 20-item scale exhibits validity (0.95) and reliability (0.965), ensuring its applicability in future research.

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4. Alnakhli AM, Saleh A, Kabel AM, Estfanous RS, Borg HM, Alsufyani KM, Sabry NM, Gomaa FAM, Abd Elmaaboud MA. Perindopril Ameliorates Sodium Valproate-Induced Rat Model of Autism: Involvement of Sirtuin-1, JAK2/STAT3 Axis, PI3K/Akt/GSK-3β Pathway, and PPAR-Gamma Signaling. Medicina (Kaunas). 2024; 60(11).

Background and Objectives: Autism is a developmental disability characterized by impairment of motor functions and social communication together with the development of repetitive or stereotyped behaviors. Neither the exact etiology or the curative treatment of autism are yet completely explored. The goals of this study were to evaluate the possible effects of perindopril on a rat model of autism and to elucidate the possible molecular mechanisms that may contribute to these effects. Materials and Methods: In a rat model of sodium valproate (VPA)-induced autism, the effect of postnatal administration of different doses of perindopril on growth and motor development, social and repetitive behaviors, sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling in the hippocampal tissues were investigated. The histopathological and electron microscopic changes elicited by administration of the different treatments were also investigated. Results: Perindopril dose-dependently combatted the effects of prenatal exposure to VPA on growth and maturation, motor development, and social and repetitive behaviors. In addition, the different doses of perindopril ameliorated the effects of prenatal exposure to VPA on sirtuin-1, oxidative stress and inflammatory markers, PI3K/Akt/GSK-3β pathway, JAK2/STAT3 axis, and PPAR-gamma signaling. These effects had a mitigating impact on VPA-induced histopathological and electron microscopic changes in the hippocampal tissues. Conclusions: Perindopril may emerge as a promising agent for amelioration of the pathologic changes of autism spectrum disorders.

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5. Angelis LO, Orsati FT, Teixeira M. LEGO(®)-Based Therapy in School Settings for Social Behavior Stimulation in Children with Autism Spectrum Disorder: Comparing Peer-Mediated and Expert Intervention. Brain Sci. 2024; 14(11).

BACKGROUND: LEGO(®)-based therapy is a social development protocol that uses LEGO(®) activities to support the development of a wide range of interaction skills, enhancing prosocial behaviors and mitigating the challenges associated with mental health difficulties and behavioral issues commonly observed in children with autism spectrum disorder (ASD). OBJECTIVES: This study aimed to explore the effects of LEGO(®)-based therapy on the social behavior and mental health of children with ASD, comparing stimulation mediated by expert and stimulation mediated by non-autistic peers. This study was approved by the Ethical Committee at Mackenzie Presbyterian University, ensuring adherence to ethical standards throughout the research process. METHODS: This study involved 18 children with ASD, levels 1 or 2, with an intelligence quotient (IQ) above 70, and three typically developing peers, intelligence quotient (IQ) above 80, aged between 5 and 8 years old, of both sexes. Participants were randomized into three groups for stimulation (stimulation mediated by expert, by a non-autistic peer and control group). The measures were the Wechsler Abbreviated Scale of Intelligence, the Strengths and Difficulties Questionnaire (parent and teacher versions), the Inventory of Difficulties in Executive Functions, Regulation, and Aversion to Delay-Child Version, the Developmental Coordination Disorder Questionnaire, the Autism Behavior Checklist, and the Autistic Behavior Inventory. RESULTS: After 14 sessions of 45 min in school settings, the participants of both groups (mediated by experts and non-autistic children) showed significant gains on social behavior. A statistically significant difference was observed between baseline sessions and probes (χ(2) (5) = 25.905, p < 0.001). These gains were maintained in both follow-up points, 30 and 90 days after the completion of the stimulation sessions. Additionally, maladaptive behavior showed a significant decline when compared pre- and post-intervention. These improvements were sustained during follow-up assessments at 30 and 90 days. CONCLUSIONS: The results suggest that a structured intervention combined with peer-mediated stimulation may be an effective method for promoting adaptive and prosocial behaviors in children with ASD.

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6. Arafuka S, Torii Y, Fujishiro H, Sekiguchi H, Miwa A, Habuchi C, Sasada K, Yoshida M, Iritani S, Iwasaki Y, Ikeda M. Premorbid autistic traits in phenocopy syndrome of behavioral variant frontotemporal dementia: An autopsy revealing primary age-related tauopathy. Asian J Psychiatr. 2024; 103: 104314.

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7. Bašić-Čičak D, Hasić Telalović J, Pašić L. Utilizing Artificial Intelligence for Microbiome Decision-Making: Autism Spectrum Disorder in Children from Bosnia and Herzegovina. Diagnostics (Basel). 2024; 14(22).

BACKGROUND/OBJECTIVES: The study of microbiome composition shows positive indications for application in the diagnosis and treatment of many conditions and diseases. One such condition is autism spectrum disorder (ASD). We aimed to analyze gut microbiome samples from children in Bosnia and Herzegovina to identify microbial differences between neurotypical children and those with ASD. Additionally, we developed machine learning classifiers to differentiate between the two groups using microbial abundance and predicted functional pathways. METHODS: A total of 60 gut microbiome samples (16S rRNA sequences) were analyzed, with 44 from children with ASD and 16 from neurotypical children. Four machine learning algorithms (Random Forest, Support Vector Classification, Gradient Boosting, and Extremely Randomized Tree Classifier) were applied to create eight classification models based on bacterial abundance at the genus level and KEGG pathways. Model accuracy was evaluated, and an external dataset was introduced to test model generalizability. RESULTS: The highest classification accuracy (80%) was achieved with Random Forest and Extremely Randomized Tree Classifier using genus-level taxa. The Random Forest model also performed well (78%) with KEGG pathways. When tested on an independent dataset, the model maintained high accuracy (79%), confirming its generalizability. CONCLUSIONS: This study identified significant microbial differences between neurotypical children and children with ASD. Machine learning classifiers, particularly Random Forest and Extremely Randomized Tree Classifier, achieved strong accuracy. Validation with external data demonstrated that the models could generalize across different datasets, highlighting their potential use.

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8. Brandes-Aitken A, Powers R, Wren J, Chu R, Shapiro KA, Steele M, Mukherjee P, Marco EJ. Sensory processing subtypes relate to distinct emotional and behavioral phenotypes in a mixed neurodevelopmental cohort. Sci Rep. 2024; 14(1): 29326.

Children with autism and other neurodevelopmental concerns (NDC) frequently exhibit an array of sensory processing dysfunction phenotypes, posing a significant challenge their adaptive development. Additionally, these children often encounter difficulties with self-regulation, including emotion dysregulation, anxiety, and symptoms associated with attention and hyperactivity. However, further research is required to comprehend how patterns of sensory processing differences across neurodevelopmental conditions may contribute to regulatory control problems. Adopting a transdiagnostic perspective within the Research Domain Criteria (RDoC) framework, this study examined the relationship between clusters of sensory processing phenotypes and differential patterns of self-regulation behaviors. We recruited a sample of 117 participants (8-12 years) with a diverse range of neurodevelopmental concerns including autism, ADHD, anxiety, and sensory processing differences. This study aimed to (1) establish the prevalence of self-regulation problems in a community-recruited cohort of children with diverse NDCs; (2) construct data-driven sensory processing latent subtypes; (3) investigate group differences in emotion dysregulation, anxiety, and ADHD symptoms. Results showed that 39% of NDC children met clinically concerning thresholds for emotion dysregulation, 19% for anxiety, and 62% for ADHD. Second, latent profile analysis identified five sensory processing subtypes categorized by modality: Typical Processing, Intermediate/Mixed, Sensory Over-Responsive, Sensory Seeking, and Sensory Under-Responsive. Notably, the Sensory Over-Responsive group exhibited distinctively elevated anxiety scores, while the Sensory Seeking and Sensory Under-Responsive groups showed heightened ADHD scores. Intriguingly, the Sensory Over-Responsive, Sensory Under-Responsive, and Sensory Seeking subgroups all demonstrated elevated emotion dysregulation scores, suggesting a potential shared mechanism of emotion dysregulation that might elucidate the connection between sensory processing differences and increased anxiety and ADHD behaviors in children with autism and other NDCs.

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9. Carbonell-Roig J, Aaltonen A, Wilson K, Molinari M, Cartocci V, McGuirt A, Mosharov E, Kehr J, Lieberman OJ, Sulzer D, Borgkvist A, Santini E. Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders. Cell Rep. 2024; 43(12): 114997.

Autism spectrum disorder (ASD) consists of diverse neurodevelopmental conditions where core behavioral symptoms are critical for diagnosis. Altered dopamine (DA) neurotransmission in the striatum has been suggested to contribute to the behavioral features of ASD. Here, we examine DA neurotransmission in a mouse model of ASD characterized by elevated expression of eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation, using a comprehensive approach that encompasses genetics, behavior, synaptic physiology, and imaging. The results indicate that increased eIF4E expression leads to behavioral inflexibility and impaired striatal DA release. The loss of normal DA neurotransmission is due to a defect in nicotinic receptor signaling that regulates calcium dynamics in dopaminergic axons. These findings provide a mechanistic understanding of ASD symptoms and offer a foundation for targeted therapeutic interventions by revealing the intricate interplay between eIF4E, DA neurotransmission, and behavioral flexibility.

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10. Chen J, Chen C, Xu R, Liu L. Autism Identification Based on the Intelligent Analysis of Facial Behaviors: An Approach Combining Coarse- and Fine-Grained Analysis. Children (Basel). 2024; 11(11).

BACKGROUND: Facial behavior has emerged as a crucial biomarker for autism identification. However, heterogeneity among individuals with autism poses a significant obstacle to traditional feature extraction methods, which often lack the necessary discriminative power. While deep-learning methods hold promise, they are often criticized for their lack of interpretability. METHODS: To address these challenges, we developed an innovative facial behavior characterization model that integrates coarse- and fine-grained analyses for intelligent autism identification. The coarse-grained analysis provides a holistic view by computing statistical measures related to facial behavior characteristics. In contrast, the fine-grained component uncovers subtle temporal fluctuations by employing a long short-term memory (LSTM) model to capture the temporal dynamics of head pose, facial expression intensity, and expression types. To fully harness the strengths of both analyses, we implemented a feature-level attention mechanism. This not only enhances the model’s interpretability but also provides valuable insights by highlighting the most influential features through attention weights. RESULTS: Upon evaluation using three-fold cross-validation on a self-constructed autism dataset, our integrated approach achieved an average recognition accuracy of 88.74%, surpassing the standalone coarse-grained analysis by 8.49%. CONCLUSIONS: This experimental result underscores the improved generalizability of facial behavior features and effectively mitigates the complexities stemming from the pronounced intragroup variability of those with autism, thereby contributing to more accurate and interpretable autism identification.

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11. Cohen O, Sukenik N. Mathematical Proficiency in Adolescents with ASD. J Autism Dev Disord. 2024.

This study aimed to investigate the mathematical abilities of adolescents with Autism Spectrum Disorder (ASD) compared to typically developing (TD) peers, focusing on procedural thinking, arithmetic comprehension, and algebraic technique. Sixty-seven adolescents (31 with ASD, 36 TD) participated in the study. A comprehensive mathematics skills test, incorporating oral and written components, was individually administered to assess abilities across three main mathematical domains. The study employed a mixed-methods approach, combining quantitative analyses of group differences with qualitative assessments of response patterns. Significant differences were observed between ASD and TD groups across most mathematical measures, with TD adolescents generally outperforming those with ASD. Large effect sizes were noted in procedural thinking and algebraic procedures. However, no significant differences were found in word problem-solving. Within the ASD group, considerable variability was observed, with some individuals demonstrating age-appropriate mathematical abilities while others showed consistently low performance across all domains. The study highlights the complex nature of mathematical abilities in adolescents with ASD, characterized by significant group differences and within-group variability. These findings highlight the importance of individualized approaches in mathematical education for adolescents with ASD and emphasize the need for early identification and targeted interventions to address specific challenges in mathematical learning.

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12. Dimov S, Shields M, Dickinson H, Kavanagh AM, White B, Sutherland G. Mental health and post-school transitions for young people with Intellectual and Developmental Disabilities (IDD): A scoping review. J Child Adolesc Ment Health. 2024: 1-30.

Background: Young people with an Intellectual and Developmental Disability (IDD) often face ineffective and exclusionary post-school transition practices, leading to poor mental health in early adulthood.Objective: This scoping review aimed to map existing literature on mental health for young people with IDD during the post-school transition period including how IDD and mental health are characterised in this context and the extent to which community members with lived experience are included in the design and/or production of research.Methods: In collaboration with a co-researcher, we used the JBI framework and PRISMA guidelines in accordance with a published protocol. A tiered search was conducted in PsycINFO, Medline, ERIC, Web of Science, and Family and Society Studies Worldwide.Findings: The search identified 28 articles that met the inclusion criteria. Articles were published between 2011 and 2023 and conducted across four countries. Thirteen applied a quantitative study design, eight were qualitative, three used a mixed-methods design, and the remaining were reviews. Most articles focused on autism. The majority discussed mental health in terms of its impact on transitioning from school or as a co-occurring condition.Conclusions: There is a growing body of literature highlighting the challenges young people with disabilities face when transitioning from high school. However, there is a notable gap in the representation of diverse IDD populations and mental health emerged variably, often as an incidental finding rather than a primary focus.

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13. El-Ansary A, Alhakbany M, Alfawaz HA, Al-Ayadhi LY. Indian Hedgehog (IHh) Protein and COX-2 as Biomarkers to Define the Mechanism of Epilepsy and Gastrointestinal Problems as Comorbid Medical Illnesses in Autism Spectrum Disorder: Combining ROC Curves to Improve Diagnostic Values. J Clin Med. 2024; 13(22).

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is increasing throughout the world. Nevertheless, no specific diagnostic or even risk assessment marker is available. Combining more than one marker can improve the diagnostic value of each marker alone and maximize the AUC for ROC curve. Hedgehog (Hh) signaling modulates both intestinal inflammation and immunity. Cyclooxygenase-2 (COX-2) is required for inflammation, and it has been related to epileptic seizures. COX-2 generates prostaglandins-EP2 (PGE2) in the brain, which plays a major role in neuropathology and epilepsy. This study aims to understand the pathophysiology of ASD by investigating the diagnostic value of COX-2 and IHh using independent and combined ROC curves. Methods: COX-2 and IHh were measured in 40 children with ASD and 41 age and sex-matched controls using ELISA. Statistical analyses were performed using ROC curves, odds ratios, and multiple logistic regression models. Results: Higher levels of COX-2 and IHh were observed in the plasma of patients with autism than in controls. The ROC curve of HIh and COX-2 independently showed poor and fair AUCs of 0.662 and 0.776, respectively, while the combined ROC for both variables in relation to the control group increased the AUC = 0.831 significantly (p < 0.001). Conclusions: Thus, combining these variables could be a useful diagnostic marker for ASD.

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14. Gaspar JM, Ferreira JP, Carvalho HM, Toscano CVA. Metabolic and Inflammatory Profiles in Children and Adolescents with Autism Spectrum Disorder: A Cross-Sectional Study. Brain Sci. 2024; 14(11).

BACKGROUND/OBJECTIVES: Autism spectrum disorder (ASD) is associated with several coexisting diseases or comorbidities, including inflammatory and metabolic disorders. In fact, ASD symptoms may be associated with immune system dysfunction. However, studies investigating the peripheral blood levels of immune cells are lacking and have provided mixed findings. In this study, we evaluated the relationship between the intensity level of ASD symptoms and the inflammatory and metabolic profiles in 154 children and adolescents (2-17 years). METHODS: Bayesian multilevel models were used to examine the relationship between their symptom intensities and inflammatory/metabolic profiles. RESULTS: Heavier children had higher values for triglyceride and insulin levels. Children with a level 3 of ASD intensity had higher free fatty acids levels. However, when adjusting for ASD intensity, gender, medication use, or weight status, older children appeared to have higher values of triglycerides, insulin levels, and free fatty acids. CONCLUSIONS: We concluded that as Brazilian children with ASD became older, they had a higher risk for insulin resistance.

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15. Genovesi E, Grant S, Kifle TH, Li J, Shand AJ, Hoekstra RA. Community involvement in PhD students’ autism research projects: Challenges and opportunities. Autism. 2024: 13623613241300683.

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16. Hersh M, Mery P, Dawson M. Older Autistic People, Access and Experiences of Services, and the Factors That Affect This. Int J Environ Res Public Health. 2024; 21(11).

This paper presents new empirical data obtained from interviews and focus groups on older (50 and over) autistic people’s experiences of accessing a variety of services. The involvement of older autistic people and giving voice to their experiences was central to all aspects of the research process. This work makes a significant contribution to the scarce literature on older autistic people. In particular, it discusses the factors that act as barriers and enablers to the access to and productive use of services, the strategies used by participants to manage and improve their experiences, and the success of these strategies. It shows older autistic people as autonomous adults and active protagonists in their own lives, taking action to overcome the barriers they experience to accessing services on the same terms as everyone else, but that lack of understanding and support from service providers and the general public can undermine their strategies. Finally, this work provides a series of recommendations for service providers to improve (older) autistic people’s service access and experiences.

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17. Hilal ML, Rosina E, Pedini G, Restivo L, Bagni C. Dysregulation of the mTOR-FMRP pathway and synaptic plasticity in an environmental model of ASD. Mol Psychiatry. 2024.

Autism Spectrum Disorder (ASD) is caused by genetic, epigenetic, and environmental factors. Mutations in the human FMR1 gene, encoding the Fragile X Messenger Ribonucleoprotein 1 (FMRP), cause the most common monogenic form of ASD, the Fragile X Syndrome (FXS). This study explored the interaction between the FMR1 gene and a viral-like infection as an environmental insult, focusing on the impact on core autistic-like behaviors and the mGluR1/5-mTOR pathway. Pregnant heterozygous Fmr1 mouse females were exposed to maternal immune activation (MIA), by injecting the immunostimulant Poly (I:C) at the embryonic stage 12.5, simulating viral infections. Subsequently, ASD-like behaviors were analyzed in the adult offspring, at 8-10 weeks of age. MIA exposure in wild-type mice led to ASD-like behaviors in the adult offspring. These effects were specifically confined to the intrauterine infection, as immune activation at later stages, namely puberty (Pubertal Immune Activation, PIA) at post-natal day 35 or adulthood (Adult Immune Activation, AIA) at post-natal day 56, did not alter adult behavior. Importantly, combining the Fmr1 mutation with MIA exposure did not intensify core autistic-like behaviors, suggesting an occlusion effect. Mechanistically, MIA provided a strong activation of the mGluR1/5-mTOR pathway, leading to increased LTP and downregulation of FMRP specifically in the hippocampus. Finally, FMRP modulates mTOR activity via TSC2. These findings further strengthen the key role of the mGluR1/5-mTOR pathway in causing ASD-like core symptoms.

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18. Hsiung EY, Chien SH. Autistic adults exhibit holistic face processing: evidence from inversion and composite face effects. Front Neurosci. 2024; 18: 1393987.

Holistic processing is commonly measured by the face inversion effect (FIE) and the composite face effect (CFE). Previous studies examining whether individuals with autism spectrum disorder (ASD) employ holistic processing using either FIE or CFE have reported inconclusive results. By adopting a customized composite face paradigm, the present study aims to simultaneously assess both the inversion and the composite effects of holistic processing in autistic and neurotypical adults. We tested 24 adults with ASD and 24 neurotypical (NT) adults matched in age, gender, and years of education. Participants viewed sequentially presented composite faces in three Presentation Modes (aligned, inverted, and misaligned) with three Stimuli Conditions (same, composite, and different) and judged whether the top half was the same. For the dependent variables, we calculated a « performance index » in the form of the accuracy/response time of each stimuli condition in each presentation mode. The FIE and CFE were computed to index the magnitude of holistic processing. Our results showed that the NT group responded more accurately in less time than the ASD group across task conditions. Notably, both the NT and the ASD groups exhibited a significant FIE with similar magnitude. Likewise, both the NT and the ASD groups showed a greater-than-zero CFE. Moreover, individuals’ CFE positively correlated with FIE and negatively correlated with the AQ scores for all participants. In summary, individuals with ASD exhibit holistic processing when viewing faces, evidenced by the presence of both FIE and CFE and the positive correlations between the two effects.

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19. Jasenovec T, Radosinska D, Belica I, Raskova B, Puzserova A, Vrbjar N, Radosinska J. Examining Erythrocytes as Potential Blood Biomarkers for Autism Spectrum Disorder: Their Relationship to Symptom Severity and Adaptive Behavior. Biomedicines. 2024; 12(11).

BACKGROUND: Multiple research teams have documented various abnormalities in erythrocyte properties in children with autism spectrum disorder (ASD) compared with neurotypical individuals. Reduced erythrocyte deformability, a crucial factor for microcirculation and oxygen delivery, may affect brain function. Other key factors like nitric oxide (NO) and Na,K-ATPase-regulated cation transport also play roles in both erythrocyte deformability and ASD, suggesting a possible relationship between erythrocyte parameters and autism severity. Thus, this study aims to describe these associations, exploring erythrocyte properties as potential biomarkers in ASD. METHODS: A total of 179 ASD children were enrolled in this study. Diagnosis was confirmed by the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Autism Diagnostic Interview-Revised. The Vineland Adaptive Behavior Scales, Third Edition (VABS-3), was used to assess adaptive behavior. RBC deformability was measured using a filtration technique, while NO production by RBCs was assessed via DAF-2DA fluorescence. Na,K-ATPase kinetics and RBC osmotic resistance were evaluated spectrophotometrically. RESULTS: Children with more severe ASD symptoms had more impaired deformability and osmotic resistance than children with mild symptoms. Higher RBC NO production was linked to better scores in some VABS-3 subdomains, and in the social affect domain of ADOS-2. Higher affinity of Na,K-ATPase for sodium negatively correlated with the occurrence of repetitive and restricted behavior-one of the core ASD symptoms. CONCLUSIONS: This study identified potential links between ASD severity and RBC properties. While erythrocyte quality can influence ASD symptomatology, the observed relationships-such as those involving RBC deformability, NO production, Na,K-ATPase kinetics, and osmotic resistance-were not strong or consistent enough to be considered reliable diagnostic or prognostic biomarkers.

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20. Jawed B, Esposito JE, Pulcini R, Zakir SK, Botteghi M, Gaudio F, Savio D, Martinotti C, Martinotti S, Toniato E. The Evolving Role of Cannabidiol-Rich Cannabis in People with Autism Spectrum Disorder: A Systematic Review. Int J Mol Sci. 2024; 25(22).

Autism spectrum disorder (ASD) is a neurological disease and lifelong condition. The treatment gap in ASD has led to growing interest in alternative therapies, particularly in phytocannabinoids, which are naturally present in Cannabis sativa. Studies indicate that treatment with cannabidiol (CBD)-rich cannabis may possess the potential to improve fundamental ASD symptoms as well as comorbid symptoms. This systematic review aims to assess the safety and efficacy of CBD-rich cannabis in alleviating the symptoms of ASD in both children and adults, addressing the treatment gap and growing interest in CBD as an alternative treatment. A comprehensive literature search was conducted in February 2024 using the PUBMED and Scopus databases while following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search focused on studies from 2020 onward involving human populations diagnosed with ASD and treated with CBD. Four studies met the inclusion criteria and were analyzed. The review included 353 participants with ASD from studies conducted in Israel, Turkey, and Brazil. The studies varied in design, sample size, dose, and treatment duration. Dosages of CBD were often combined with trace amounts of THC. Improvements were noted in behavioral symptoms, social responsiveness, and communication, but cognitive benefits were less consistent. Adverse effects ranged in severity. Mild effects such as somnolence and decreased appetite were common, while more concerning effects, including increased aggression, led to some cases of treatment discontinuation. CBD-rich cannabis shows promise in improving behavioral symptoms associated with ASD. However, variations in study designs, dosages, and outcome measures highlight the need for standardized assessment tools and further research to understand pharmacological interactions and optimize treatment protocols. Despite the mild adverse effects observed, larger, well-controlled trials are necessary to establish comprehensive safety and efficacy profiles.

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21. Jeon I, Kim M, So D, Kim EY, Nam Y, Kim S, Shim S, Kim J, Moon J. Reliable Autism Spectrum Disorder Diagnosis for Pediatrics Using Machine Learning and Explainable AI. Diagnostics (Basel). 2024; 14(22).

Background: As the demand for early and accurate diagnosis of autism spectrum disorder (ASD) increases, the integration of machine learning (ML) and explainable artificial intelligence (XAI) is emerging as a critical advancement that promises to revolutionize intervention strategies by improving both accuracy and transparency. Methods: This paper presents a method that combines XAI techniques with a rigorous data-preprocessing pipeline to improve the accuracy and interpretability of ML-based diagnostic tools. Our preprocessing pipeline included outlier removal, missing data handling, and selecting pertinent features based on clinical expert advice. Using R and the caret package (version 6.0.94), we developed and compared several ML algorithms, validated using 10-fold cross-validation and optimized by grid search hyperparameter tuning. XAI techniques were employed to improve model transparency, offering insights into how features contribute to predictions, thereby enhancing clinician trust. Results: Rigorous data-preprocessing improved the models’ generalizability and real-world applicability across diverse clinical datasets, ensuring a robust performance. Neural networks and extreme gradient boosting models achieved the best performance in terms of accuracy, precision, and recall. XAI techniques demonstrated that behavioral features significantly influenced model predictions, leading to greater interpretability. Conclusions: This study successfully developed highly precise and interpretable ML models for ASD diagnosis, connecting advanced ML methods with practical clinical application and supporting the adoption of AI-driven diagnostic tools by healthcare professionals. This study’s findings contribute to personalized intervention strategies and early diagnostic practices, ultimately improving outcomes and quality of life for individuals with ASD.

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22. Jończyk J, Przybylska K, Staszewski M, Godyń J, Werner T, Stefaniak-Napieralska M, Stark H, Walczyński K, Bajda M. Virtual Screening Approaches to Identify Promising Multitarget-Directed Ligands for the Treatment of Autism Spectrum Disorder. Molecules. 2024; 29(22).

Autism spectrum disorder is a complex neurodevelopmental disorder. The available medical treatment options for autism spectrum disorder are very limited. While the etiology and pathophysiology of autism spectrum disorder are still not fully understood, recent studies have suggested that wide alterations in the GABAergic, glutamatergic, cholinergic, and serotonergic systems play a key role in its development and progression. Histamine neurotransmission is known to have complex interactions with other neurotransmitters that fit perfectly into the complex etiology of this disease. Multitarget-directed compounds with an affinity for the histamine H(3) receptor indicate an interesting profile of activity against autism spectrum disorder in animal models. Here, we present the results of our research on the properties of (4-piperazin-1-ylbutyl)guanidine derivatives acting on histamine H(3) receptors as potential multitarget ligands. Through the virtual screening approach, we identified promising ligands among 32 non-imidazole histamine H(3) receptor antagonists/inverse agonists with potential additional activity against the dopamine D(2) receptor and/or cholinesterases. The virtual screening protocol integrated predictions from SwissTargetPrediction, SEA, and PPB2 tools, along with molecular docking simulations conducted using GOLD 5.3 and Glide 7.5 software. Among the selected ligands, compounds 25 and 30 blocked radioligand binding to the D(2) receptor at over 50% at a screening concentration of 1 µM. Further experiments allowed us to determine the pK(i) value at the D(2) receptor of 6.22 and 6.12 for compounds 25 and 30, respectively. Our findings suggest that some of the tested compounds could be promising multitarget-directed ligands for the further research and development of more effective treatments for autism spectrum disorder.

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23. Ju Y, Kang S, Kim J, Ryu JK, Jeong EH. Clinical Utility of Virtual Kitchen Errand Task for Children (VKET-C) as a Functional Cognition Evaluation for Children with Developmental Disabilities. Children (Basel). 2024; 11(11).

BACKGROUND/OBJECTIVES: This study evaluated the clinical utility of a virtual reality (VR)-based kitchen error task for children (VKET-C) to assess functional cognition in children. METHODS: In total, 38 children aged 7-12 years were included, comprising 23 typically developing (TD) children and 15 children with developmental disabilities (DDs), including autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability. While performing the VKET-C, performance errors were analyzed. The Stockings of Cambridge (SOC) and Spatial Working Memory (SWM) tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive function. The Brunner-Munzel test was performed to compare performance errors between the TD and DD groups, and correlations between performance errors and cognitive measures were analyzed. RESULTS: Omission and commission errors were significantly different between the groups (p < 0.001), with no significant difference in motor errors (p > 0.05). Omission errors were correlated with the initial thinking time mean (ITMN) in all items of the SOC task and the between errors (BE) of the SWM task. Commission errors were correlated with the ITMN in the difficult items of the SOC task and the BE of the SWM task. Additionally, motor errors were significantly correlated with problems solved in minimum moves (PSMM) and ITMN in the difficult items of the SOC task and BE in the SWM task. CONCLUSIONS: The VKET-C shows promise as an effective tool for assessing executive function and working memory in children with DDs, offering an engaging and ecologically valid alternative to traditional methods.

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24. Kadekaru R, Okanishi T, Maegaki Y, Inoue M. Effectiveness of Online Parent Training for Parents of Adolescents with Developmental Disabilities: A Retrospective Observational Study Comparing Clinical- and Community-Based Online Parent Training. Yonago Acta Med. 2024; 67(4): 341-54.

BACKGROUND: Parent training (PT) is an effective program for improving the parenting skills and mental health of parents of children with developmental disabilities (DD) and for improving children’s behavioral problems. However, studies must substantiate the effectiveness of PT for the parents of adolescents with DD in improving parental mental health and children’s problem behaviors with ample scientific evidence. This study is a retrospective observational study and has two objectives. The first is to examine the effectiveness of online adolescent PT (ON-APT), in which lectures on counseling skills are incorporated for the parents of adolescents with DD. The second aim is to examine the effects of different delivery conditions on community- and clinical-based ON-APT. METHODS: Data from seven parents and children who participated in community-based ON-APT and 14 parents and 12 children who participated in clinical-based ON-APT were included in the analysis. Prior to the intervention (pre-test) and after the intervention (post-test), paired t-tests were conducted using the CBCL, BDI-II, and PATS scores to demonstrate the effectiveness of the ON-APT program. Second, a two-way repeated measures analysis of variance with aligned rank transform was conducted to assess the impact of varying ON-APT delivery conditions (clinical- versus community-based ON-APT) and time (pre- and post-tests) on the outcome variables. RESULTS: ON-APT resulted in significant improvements in some children’s problem behaviors (withdrawal). Community-based ON-APT resulted in improvements in some children’s problem behaviors (total score, withdrawal, and social problems scales) compared with clinical-based ON-APT. CONCLUSION: This study shows the potential effectiveness of ON-APT, in which lectures on counseling skills are incorporated for parents of adolescents with DD. Further, a comparison between clinical-based and community-based ON-APT showed that integrating face-to-face consultations into ON-APT may improve children’s problem behaviors. However, this study provides preliminary evidence for its potential efficacy, and future studies should demonstrate this efficacy through a validation design.

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25. Klavina A, Pérez-Fuster P, Daems J, Lyhne CN, Dervishi E, Pajalic Z, Øderud T, Fuglerud KS, Markovska-Simoska S, Przybyla T, Klichowski M, Stiglic G, Laganovska E, Alarcão SM, Tkaczyk AH, Sousa C. The use of assistive technology to promote practical skills in persons with autism spectrum disorder and intellectual disabilities: A systematic review. Digit Health. 2024; 10: 20552076241281260.

Persons with autism spectrum disorder (ASD) and/or intellectual disability (ID) have difficulties in planning, organising and coping with change, which impedes the learning of daily living skills (DLSs), social participation and self-management across different environmental settings. Assistive technologies (ATs) is a broad term encompassing devices and services designed to support individuals with disabilities, and if used in a self-controlled manner, they may contribute inclusion in all domains of participation. This comprehensive literature review aims to critically assess and unify existing research that investigates the use of assistive technology within the practical domain for individuals with ASD and/or ID. The 18 relevant studies included in this review highlighted the benefits of AT for social participation and independence in daily activities of individuals with ASD and/or ID. Professionals working with this target group should be knowledgeable of the speedy progress of AT products and the potential of persons with ASD and/or ID to use mainstream devices to meet their individual needs. This awareness provides an opportunity to advocate for the universal benefits of AT for everyone. Technologies such as virtual reality, mobile applications and interactive software have been shown to improve DLSs, communication and social interaction. These tools offer engaging, user-friendly platforms that address the specific needs of these individuals, enhancing their learning and independence.

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26. Kuo CY, Liu CH, Huang YC, Liang SH, Lin HY, Ni HC. Psychometric properties of the Taiwan version of Emotion Dysregulation Inventory in Autism Spectrum Disorder. J Formos Med Assoc. 2024.

BACKGROUND: While the Emotion Dysregulation Inventory (EDI) for autistic people has been validated in many Western countries, its psychometric properties have remained unclear in East Asia. METHODS: We translated the EDI into traditional Chinese and evaluated its psychometric properties among autistic children and youth in Taiwan. We enrolled 200 participants (182 male/18 female) aged 7-30 years from five clinical trials and conducted secondary analyses, assessing internal consistency reliability, confirmatory factor analysis, and convergent validity. RESULTS: Our results showed that the Taiwan version of the EDI had strong internal consistency (Cronbach’s alpha are 0.978 and 0.864 for each factor). Confirmatory factor analysis demonstrated acceptable fit of two-factors structure. The Taiwan version of EDI showed good convergent validity with established measurements including the Aberrant Behavior Checklist-Irritability subscale and Child Behavior Checklist-Dysregulation Profile. CONCLUSION: Our findings support the Taiwan version of EDI is a reliable and potentially valid instrument for assessing emotion dysregulation in autistic children and youth in Taiwan.

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27. Lee J, Ferretti L, Nelson C, Nigam P, Zawacki J, McCallion P. Health Disparities in Hospitalized Pediatric Patients with Autism Spectrum Disorder and COVID-19. Children (Basel). 2024; 11(11).

Pediatric patients with autism spectrum disorder (ASD) face unique challenges, especially amongst individuals from historically minoritized racial groups. ASD has also been associated with an increased mortality from COVID-19. This study aims to explore the differences in sociodemographic factors and health outcomes (as measured by length of stay) amongst hospitalized pediatric patients with COVID-19 infections and a diagnosis of ASD compared to individuals with a COVID-19 infection alone; Methods: We performed a retrospective cohort study examining pediatric patients (ages birth to 21) who were hospitalized with a diagnosis of ASD and COVID-19 compared to patients with a diagnosis of COVID-19 alone between January 2019 and June 2023 using Epic Systems Corporation’s Cosmos, a de-identified dataset aggregated from electronic health record data. We examined differences in demographic factors and length of stay (LOS) between groups by utilizing chi-square and Wilcoxon rank sum tests. Multiple logistic regression models were utilized to assess the association between length of stay and diagnosis; Results: A total of 21,708 distinct pediatric patients with a diagnosis of ASD and COVID-19 or COVID-19 alone were included in the analytical dataset. Patients with ASD and COVID-19, compared to patients with COVID-19 alone, had a higher proportion of individuals identifying as male and White. Patients with COVID-19 alone, compared to individuals with ASD and COVID-19, had higher proportions of individuals identifying as Black or African American. Higher proportions of individuals with ASD and COVID-19 had public insurance, compared to individuals with COVID-19 alone. Having a diagnosis of ASD and COVID, after controlling for covariates, was associated with higher odds of having a length of stay greater than the three days (cutoff value determined by the median LOS of three days) compared to having a diagnosis of COVID alone (aOR 1.19, 95% CI 1.04-1.35); Conclusions: Our study highlights the health disparities experienced during hospitalizations by pediatric patients with ASD and COVID-19. Further studies should address barriers and support health outcomes for pediatric patients with ASD.

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28. Márquez-García AV, Vakorin VA, Kozhemiako N, Iarocci G, Moreno S, Doesburg SM. Atypical Brain Connectivity During Pragmatic and Semantic Language Processing in Children with Autism. Brain Sci. 2024; 14(11).

BACKGROUND/OBJECTIVES: Children with Autism Spectrum Disorder (ASD) face challenges in social communication due to difficulties in considering context, processing information, and interpreting social cues. This study aims to explore the neural processes related to pragmatic language communication in children with ASD and address the research question of how functional brain connectivity operates during complex pragmatic language tasks. METHODS: We examined differences in brain functional connectivity between children with ASD and typically developing peers while they engaged in video recordings of spoken language tasks. We focused on two types of speech acts: semantic and pragmatic. RESULTS: Our results showed differences between groups during the pragmatic and semantic language processing, indicating more idiosyncratic connectivity in children with ASD in the Left Somatomotor and Left Limbic networks, suggesting that these networks play a role in task-dependent functional connectivity. Additionally, these functional differences were mainly localized to the left hemisphere.

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29. Meossi C, Carrer A, Ciaccio C, Pezzoli L, Pezzani L, Silipigni RM, Sciacca FL, Tenconi R, Esposito S, De Laurentiis A, Pantaleoni C, Marchisio P, Natacci F, D’Arrigo S, Iascone M, Milani D. Looks Can Be Deceiving: Diagnostic Power of Exome Sequencing in Debunking 15q11.2 Copy Number Variations. Genes (Basel). 2024; 15(11).

Background/Objectives: The pathogenetic role of 15q11.2 Copy Number Variations (CNVs) remains contentious in the scientific community, as microdeletions and microduplications in this region are linked to neurodevelopmental disorders with variable expressivity. This study aims to explore the diagnostic utility of Exome Sequencing (ES) in a cohort of pediatric patients with 15q11.2 CNVs. Methods: We enrolled 35 probands with 15q11.2 microdeletions or microduplications from two genetic centers between January 2021 and January 2023. Chromosomal Microarray Analysis (CMA) and ES were performed with written consent obtained from all parents. Pathogenic variants were classified according to ACMG guidelines. Results: CMA identified additional pathogenic CNVs in 3 of 35 children (9%). Subsequent ES revealed likely pathogenic or pathogenic variants in 11 of 32 children (34%). Notably, a higher percentage of isolated autism spectrum disorder (ASD) diagnoses was observed in patients without other CNVs or point mutations (p = 0.019). Conclusions: The ES analysis provided a diagnostic yield of 34% in this pediatric cohort with 15q11.2 CNVs. While the study does not dismiss the contribution of the CNV to the clinical phenotype, the findings suggest that ES may uncover the underlying causes of neurodevelopmental disorders. Continuous monitoring and further genetic testing are recommended for all 15q11.2 CNV carriers to optimize clinical management and familial counseling.

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30. Mihailovich M, Tolinački M, Soković Bajić S, Lestarevic S, Pejovic-Milovancevic M, Golić N. The Microbiome-Genetics Axis in Autism Spectrum Disorders: A Probiotic Perspective. Int J Mol Sci. 2024; 25(22).

Autism spectrum disorder (commonly known as autism) is a complex and prevalent neurodevelopmental condition characterized by challenges in social behavior, restricted interests, and repetitive behaviors. It is projected that the annual cost of autism spectrum disorder in the US will reach USD 461 billion by 2025. However, despite being a major public health problem, effective treatment for the underlying symptoms remains elusive. As numerous literature data indicate the role of gut microbiota in autism prognosis, particularly in terms of alleviating gastrointestinal (GI) symptoms, high hopes have been placed on probiotics for autism treatment. Approximately twenty clinical studies have been conducted using single or mixed probiotic cultures. However, unequivocal results on the effect of probiotics on people with autism have not been obtained. The small sample sizes, differences in age of participants, choice of probiotics, dose and duration of treatment, outcome measures, and analytical methods used are largely inconsistent, making it challenging to draw distinctive conclusions. Here, we discuss the experimental evidence for specific gut bacteria and their metabolites and how they affect autism in light of the phenotypic and etiological complexity and heterogeneity. We propose a personalized medicine approach for using probiotics to increase the quality of life of individuals with autism by selecting specific probiotics to improve particular features of the condition.

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31. Mongad D, Subramanian I, Krishanpal A. Deriving comprehensive literature trends on multi-omics analysis studies in autism spectrum disorder using literature mining pipeline. Front Neurosci. 2024; 18: 1400412.

Autism spectrum disorder (ASD) is characterized by highly heterogenous abnormalities in functional brain connectivity affecting social behavior. There is a significant progress in understanding the molecular and genetic basis of ASD in the last decade using multi-omics approach. Mining this large volume of biomedical literature for insights requires considerable amount of manual intervention for curation. Machine learning and artificial intelligence fields are advancing toward simplifying data mining from unstructured text data. Here, we demonstrate our literature mining pipeline to accelerate data to insights. Using topic modeling and generative AI techniques, we present a pipeline that can classify scientific literature into thematic clusters and can help in a wide array of applications such as knowledgebase creation, conversational virtual assistant, and summarization. Employing our pipeline, we explored the ASD literature, specifically around multi-omics studies to understand the molecular interplay underlying autism brain.

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32. Ng-Cordell E, Pickard H, Bedford R, Richard A, Zaidman-Zait A, Zwaigenbaum L, Duku E, Bennett T, Georgiades S, Smith IM, Vaillancourt T, Szatmari P, Elsabbagh M, Kerns CM. Longitudinal associations between autistic children’s anxiety and social communication differences: The moderating role of executive function behaviours. Autism. 2024: 13623613241296589.

Anxiety is a mental health concern affecting many autistic children, and has been linked to greater differences in social communication and interaction style. Executive functioning (i.e. the ability to direct and regulate attention and behaviour) plays an important role in autistic children’s and social-emotional development. We tested whether anxiety (reported by parents) predicts social communication and interaction differences (reported by teachers) over time or vice versa among autistic preadolescents. We also investigated whether the link between anxiety and social communication and interaction differed depending on children’s EF abilities (reported by teachers). We found less parent-reported anxiety predicted more teacher-reported social communication and interaction differences a year later – but only for children who had heightened behavioural dysregulation (an aspect of executive functioning that includes impulse and emotion control). Our work suggests autistic preadolescents with behavioural dysregulation and limited anxiety may be at greater risk for social difficulties, and may need more support in this area. Executive functioning may be a useful mechanism to target in treatment for this group of children.

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33. Pangrazzi L, Cerilli E, Balasco L, Dall’O’ G M, Chelini G, Pastore A, Weinberger B, Bozzi Y. N-Acetylcysteine Counteracts Immune Dysfunction and Autism-Related Behaviors in the Shank3b Mouse Model of Autism Spectrum Disorder. Antioxidants (Basel). 2024; 13(11).

Autism spectrum disorder (ASD) includes a range of neurodevelopmental disabilities characterized by social interaction deficits, communication impairments, and repetitive behaviors. Previous studies have shown that pro-inflammatory conditions play a key role in ASD. Despite this, how oxidative stress and inflammation may contribute to ASD-related behaviors is still poorly understood. Here, we reported that increased levels of molecules related to inflammation are present in the cerebellum and peripheral blood (PB) of mice lacking Shank3b, an established model of syndromic ASD. In parallel, immune dysfunction was documented in the bone marrow (BM) and spleens of mutant mice. N-acetylcysteine (NAC) treatment rescued inflammation in the cerebellum and PB and impaired the production of pro-inflammatory molecules in the BM and spleen. In addition, social impairment was counteracted in NAC-treated Shank3b(-/-) animals. Taken together, our results provide clear evidence of the key role of cerebellar oxidative stress and inflammation in the establishment of ASD-related behaviors. Furthermore, our findings underscore the importance of considering ASD as a systemic disorder.

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34. Qi M, Chen W, Qi G, Yuan P, Hu X, Xiang J, Xiao D, Chu X, Shi X. The predictive effect of ASD on PTSD and the factors influencing ASD and PTSD. Injury. 2024; 56(2): 112033.

OBJECTIVE: To investigate the prevalence and influencing factors of acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) in trauma patients, and to explore the predictive effect of ASD on PTSD. METHODS: A prospective study was conducted on patients hospitalized due to injuries. The first survey used the ASD scale to assess the occurrence of ASD. In one month and three months of follow-up after injury, patients were assessed for the occurrence of PTSD by using the PTSD checklist-civilian version. RESULTS: The prevalence rates of ASD, one-month PTSD, and three-month PTSD in trauma inpatients were 20.7%, 19.5%, and 17.6%, respectively. ASD is a strong predictor of PTSD, and combining it with severe injury and critical illness can improve the sensitivity and positive predictive ability of predicting the occurrence of PTSD (AUC(Max): 0.827). The important predictive factor for the diagnosis of PTSD is the high alert symptom group of ASD. Moreover, the analysis results showed that the season of trauma happened, comatose state, fear state, psychological burden, and pain intensity were the influencing factors for ASD (P<0.05), while critical illness during hospitalization, psychological burden, and pain intensity were the influencing factors for PTSD (P<0.05). LIMITATIONS: Some patients with minor and extremely serious injuries were overlooked or missed, resulting in selection bias and information bias that could not be completely avoided. CONCLUSION: Both trauma conditions and clinical features may affect the occurrence of ASD and PTSD in trauma patients. If ASD in trauma patients is identified early and targeted interventions, it may reduce the occurrence and development of PTSD.

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35. Recio P, Pozo P, García-López C, Sarriá E. Autistic Sensory Traits and Psychological Distress: Mediating Role of Worry and Intolerance of Uncertainty. Brain Sci. 2024; 14(11).

BACKGROUND/OBJECTIVES: Autistic adults exhibit core and comorbid features that can have an impact on their daily functioning and lead to considerable psychological distress. Significant and consistent associations have been identified between autism characteristics-restricted repetitive behaviors and sensory features-and high levels of stress and anxiety. For a better understanding of the issue, it is necessary to consider the cognitive aspects that can help explain variations in stress and anxiety levels among adults with autism. We therefore aimed to model the contributions of worry and intolerance of uncertainty on the relationship between autism characteristics (sensory sensitivities and repetitive behaviors) and psychological distress (stress and anxiety). METHODS: The sample comprised 144 autistic individuals with a mean age of 35.15 (SD = 11.44). They participated in the study by completing an online questionnaire to assess the study variables. Most of the participants reported being diagnosed with Asperger syndrome (63.6%) or Level 1 autism spectrum disorder (27.1%). RESULTS: The model fit index values tested through path analysis indicated a good fit (χ(2) = 5.65; p = 0.13 ns; CFI = 0.993; NFI = 0.985; RMSEA = 0.079; SRMR = 0.025) and identified worry and intolerance of uncertainty as significant mediating variables within a comprehensive explanatory model. CONCLUSIONS: These findings highlight the importance of worry and intolerance of uncertainty as specific targets in interventions aimed at improving stress and anxiety problems in autistic adults.

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36. Reddy DU, Kumar KVP, Ramakrishna B, Umaiorubagam GS. An IoT-Based Framework for Automated Assessing and Reporting of Light Sensitivities in Children with Autism Spectrum Disorder. Sensors (Basel). 2024; 24(22).

Identification of light sensitivities, manifesting either as hyper-sensitive (over-stimulating) or hypo-sensitive (under-stimulating) in children with autism spectrum disorder (ASD), is crucial for the development of personalized sensory environments and therapeutic strategies. Traditional methods for identifying light sensitivities often depend on subjective assessments and manual video coding methods, which are time-consuming, and very keen observations are required to capture the diverse sensory responses of children with ASD. This can lead to challenges for clinical practitioners in addressing individual sensory needs effectively. The primary objective of this work is to develop an automated system using Internet of Things (IoT), computer vision, and data mining techniques for assessing visual sensitivities specifically associated with light (color and illumination). For this purpose, an Internet of Things (IoT)-based light sensitivities assessing system (IoT-LSAS) was designed and developed using a visual stimulating device, a bubble tube (BT). The IoT-LSAS integrates various electronic modules for (i) generating colored visual stimuli with different illumination levels and (ii) capturing images to identify children’s emotional responses during sensory stimulation sessions. The system is designed to operate in two different modes: a child control mode (CCM) and a system control mode (SCM). Each mode uses a distinct approach for assessing light sensitivities, where CCM uses a preference-based approach, and SCM uses an emotional response tracking approach. The system was tested on a sample of 20 children with ASD, and the results showed that the IoT-LSAS effectively identified light sensitivities, with a 95% agreement rate in the CCM and a 90% agreement rate in the SCM when compared to the practitioner’s assessment report. These findings suggest that the IoT-LSAS can be used as an alternative to traditional assessment methods for diagnosing light sensitivities in children with ASD, significantly reducing the practitioner’s time required for diagnosis.

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37. Roodbarani M, Tagharrobi Z, Sharifi K, Sooki Z, Zare M. Influence of Brain Gym on children’s behavioral problems with autism spectrum disorder: A randomized controlled clinical trial. J Bodyw Mov Ther. 2024; 40: 1248-54.

INTRODUCTION: Children with autism spectrum disorder (ASD) present with a variety of behavioral problems. The aim of this study is to investigate the effectiveness of Brain Gym (BG) on the behavioral problems of children with ASD in Iran. METHODS: This clinical trial was conducted on 36 children with ASD at Kashan and Arak in 2019. Samples were selected using the block randomization method and assigned to the intervention and control groups. The intervention group received ten sessions of BG according to Dennison’s protocol. There was no intervention in the control group. The stereotyped behavior, communication, and social interactions of the behavioral problems were assessed at the beginning (T0), the end of the intervention (T1), and two months later (T2). The data were collected using the Demographics, Rutter, GARS-2, and Raven scales. Data from 33 children were analyzed via per-protocol and intention-to-treat analysis using repeated measures analysis of variance. RESULTS: The two groups did not differ significantly in demographic variables. The results showed a significant interaction effect of time and intervention on the severity of behavioral problems (p < 0.0001). There was a significant difference in the severity of behavioral disorders between the two groups at T1 and T2 (p < 0.05). A within-group analysis revealed a significant difference in the severity of the behavioral disorder at the three time points between the BG and control groups (p < 0.0001). CONCLUSION: BG can alleviate the behavioral problems of children with ASD. This intervention is recommended as a complementary treatment for affected families with children with ASD. TRIAL REGISTRATION NUMBER: IRCT20100211003329N5. DATE OF REGISTRATION: 2020-07-16.

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38. Sánchez Amate JJ, Luque de la Rosa A. The Effect of Autism Spectrum Disorder on Family Mental Health: Challenges, Emotional Impact, and Coping Strategies. Brain Sci. 2024; 14(11).

BACKGROUND: Autism Spectrum Disorder (ASD) impacts not only diagnosed individuals, but also significantly affects the quality of life of both primary and secondary caregivers. These effects are particularly pronounced when compared to caregivers of individuals with other neurodevelopmental disorders. The emotional and physical demands of caring for someone with ASD can profoundly alter family dynamics and interpersonal relationships, creating challenges that require a comprehensive approach to be understood and addressed. METHODS: The methodological design is a narrative review study, based on a search conducted during May, June, July, and August 2024 in the Scopus, Dialnet, and WoS databases concerning the object of study. As a result, a total of 197 articles were qualitatively analyzed. Of these, 36 articles were selected for a more detailed qualitative analysis, leading to a final sample of 14 documents. The selected studies were examined through qualitative content analysis. The inclusion criteria for this selection were as follows: empirical studies or research published in English or Spanish; open access via the Internet; categories limited to « education/educational research » relevant to the proposed objectives; and specific documents related to students with Autism Spectrum Disorder (ASD). RESULTS: The care of individuals with Autism Spectrum Disorder (ASD) has a significant and multifaceted impact on family life, deeply affecting the mental health of caregivers. These effects manifest in the form of chronic stress, anxiety, and interpersonal difficulties, altering family dynamics. The quality of life of caregivers varies depending on the coping strategies they employ, which are crucial for their emotional well-being. CONCLUSIONS: Understanding and optimizing these strategies is essential to mitigate the negative effects of caregiving and improving the overall well-being of families living with ASD.

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39. Scorrano G, Di Francesco L, Di Ludovico A, Chiarelli F, Matricardi S. Exploring the Landscape of Pre- and Post-Synaptic Pediatric Disorders with Epilepsy: A Narrative Review on Molecular Mechanisms Involved. Int J Mol Sci. 2024; 25(22).

Neurodevelopmental disorders (NDDs) are a group of conditions affecting brain development, with variable degrees of severity and heterogeneous clinical features. They include intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), often coexisting with epilepsy, extra-neurological comorbidities, and multisystemic involvement. In recent years, next-generation sequencing (NGS) technologies allowed the identification of several gene pathogenic variants etiologically related to these disorders in a large cohort of affected children. These genes encode proteins involved in synaptic homeostasis, such as SNARE proteins, implicated in calcium-triggered pre-synaptic release of neurotransmitters, or channel subunit proteins, such as post-synaptic ionotropic glutamate receptors involved in the brain’s fast excitatory neurotransmission. In this narrative review, we dissected emerged molecular mechanisms related to NDDs and epilepsy due to defects in pre- and post-synaptic transmission. We focused on the most recently discovered SNAREopathies and AMPA-related synaptopathies.

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40. Selvi S, Parvathy M. Improving facial expression recognition for autism with IDenseNet-RCAformer under occlusions. Int J Dev Neurosci. 2024.

The term ‘autism spectrum disorder’ describes a neurodevelopmental illness typified by verbal and nonverbal interaction impairments, repetitive behaviour patterns and poor social interaction. Understanding mental states from FEs is crucial for interpersonal interaction and social interaction. But when there are occlusions like glasses, facial hair or self-occlusion, it becomes harder to identify facial expressions accurately. This research tackles the issue of identifying facial expressions when parts of the face are occluded and suggests an innovative technique to tackle this difficulty. Creating a strong framework for facial expression recognition (FER) that better handles occlusions and increases recognition accuracy is the goal of this research. Therefore, we propose novel Improved DenseNet-based Residual Cross-Attention Transformer (IDenseNet-RCAformer) system to tackle the partial occlusion FER problem in autism patients. The recognition framework’s efficacy is assessed using four datasets of facial expressions, and some preprocessing procedures are conducted to increase the expression recognition efficiency. After that, when recognizing expressions, a simple argmax function is applied to get a forecasted landmark position from a heatmap. Then feature extraction phase, local and global representation are captured from preprocessed images by adopting Inception-ResNet-V2 approach, Cross-Attention Transformer, respectively. Moreover, both features are fused by employing the FusionNet method, thereby enhancing system’s training speed and precision. After the features are extracted, an improved DenseNet mechanism is applied to efficiently recognize some variety of facial expressions in partially occluded autism patients. A number of performance metrics are determined and analysed to demonstrate the proposed approach’s effectiveness, where the IDenseNet-RCAformer performs best with an accuracy of 98.95%. According to the experimental findings, the proposed framework significantly outperforms the prior recognition frameworks in terms of recognition outcomes.

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41. Sherawat K, Mehan S, Khan Z, Tiwari A, Gupta GD, Narula AS. Neuroprotective Potential of Tanshinone-IIA in Mitigating Propionic Acidinduced Experimental Autism-like Behavioral and Neurochemical Alterations: Insights into c-JNK and p38MAPK Pathways. Curr Mol Pharmacol. 2024.

INTRODUCTION: Autism is a neurodevelopmental disorder associated with mitochondrial dysfunction, apoptosis, and neuroinflammation. These factors can lead to the overactivation of c-JNK and p38MAPK. METHODS: In rats, stereotactic intracerebroventricular (ICV) injection of propionic acid (PPA) results in autistic-like characteristics such as poor social interaction, repetitive behaviours, and restricted communication. Research has demonstrated the beneficial effects of phytochemicals derived from plants in treating neurological disorders. Tanshinone-IIA (Tan-IIA) is a chemical found in the root of Salvia miltiorrhiza. It has neuroprotective potential by inhibiting c-JNK and p38MAPK against behavioral and neurochemical alterations in PPA-induced autistic rats. We observe behavioral changes, alterations in apoptotic markers, myelin basic protein (MBP), neurofilament-Light (NEFL), inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and neurotransmitter imbalances using different brain regions (cerebral cortex, hippocampus, striatum), as well as biological samples, cerebrospinal fluid (CSF), and blood plasma. RESULTS: Persistent administration of 30 mg/kg and 60 mg/kg Tan-IIA via intraperitoneal injection reduced these alterations dose-dependently. Anisomycin (3 mg/kg.,i.p.) as a SAPK (c-JNK and p38MAPK) agonist was administered to assess the neuroprotective effect of Tan-IIA in autistic rats. Tan- IIA’s molecular interactions with c-JNK and p38MAPK were confirmed using silico analysis. We also observed gross morphological, histopathological, and Luxol Fast Blue (LFB) myelin straining changes in whole and coronal brain sections. CONCLUSION: Thus, Tan-IIA has a neuroprotective potential by inhibiting the c-JNK and p38MAPK signalling pathways, which reduces the behavioral and neurochemical abnormalities induced by PPA in adult Wistar rats, indicating that current results should be studied further for the diagnosis and treatment of autism.

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42. Varone M, Scavo G, Colardo M, Martella N, Pensabene D, Bisesto E, Del Busso A, Segatto M. p75NTR Modulation Reduces Oxidative Stress and the Expression of Pro-Inflammatory Mediators in a Cell Model of Rett Syndrome. Biomedicines. 2024; 12(11).

Background: Rett syndrome (RTT) is an early-onset neurological disorder primarily affecting females, leading to severe cognitive and physical disabilities. Recent studies indicate that an imbalance of redox homeostasis and exacerbated inflammatory responses are key players in the clinical manifestations of the disease. Emerging evidence highlights that the p75 neurotrophin receptor (p75NTR) is implicated in the regulation of oxidative stress (OS) and inflammation. Thus, this study is aimed at investigating the effects of p75NTR modulation by LM11A-31 on fibroblasts derived from RTT donors. Methods: RTT cells were treated with 0.1 µM of LM11A-31 for 24 h, and results were obtained using qPCR, immunofluorescence, ELISA, and Western blot techniques. Results: Our findings demonstrate that LM11A-31 reduces OS markers in RTT fibroblasts. Specifically, p75NTR modulation by LM11A-31 restores protein glutathionylation and reduces the expression of the pro-oxidant enzyme NOX4. Additionally, LM11A-31 significantly decreases the expression of the pro-inflammatory mediators interleukin-6 and interleukin-8. Additionally, LM11A-31 normalizes the expression levels of transcription factors involved in the regulation of the antioxidant response and inflammation. Conclusions: Collectively, these data suggest that p75NTR modulation may represent an effective therapeutic target to improve redox balance and reduce inflammation in RTT.

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43. Vecchione R, Westlake M, Bragg MG, Rando J, Bennett DH, Croen LA, Dunlop AL, Ferrara A, Hedderson MM, Kerver JM, Lee BK, Lin PD, Hertz-Picciotto I, Schmidt RJ, Strakovsky RS, Lyall K. Maternal Dietary Patterns During Pregnancy and Child Autism-Related Traits in the Environmental Influences on Child Health Outcomes Consortium. Nutrients. 2024; 16(22).

We examined relationships between prenatal dietary patterns and child autism-related outcomes, including parent-reported clinician diagnoses of autism spectrum disorder (ASD) and Social Responsiveness Scale (SRS-2) scores, in up to 6084 participants (with analytic samples ranging from 1671 to 4128 participants) from 14 cohorts in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Associations between quartiles of the Healthy Eating Index (HEI-2015), the Alternative Healthy Eating Index modified for Pregnancy (AHEI-P), and the Empirical Dietary Inflammatory Pattern (EDIP), calculated based on reported prenatal diet, and outcomes were examined using crude and multivariable regression (quantile for SRS scores and logistic for diagnosis). In adjusted models, the higher quartile of prenatal HEI score was associated with lower SRS scores (Q4 vs. Q1 β for median quantile = -3.41 95% CI = -5.15, -1.26). A similar association was observed for the AHEI-P score when adjusting for total calories (Q4 vs. Q1 β = -2.52 95% -4.59, -0.45). There were no significant associations of prenatal diet with ASD diagnosis. Findings from this large U.S.-based study do not suggest strong associations between prenatal dietary patterns and ASD-related outcomes, although subtle associations with broader traits suggest the need to further consider how prenatal diet may relate to ASD-related phenotypes.

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44. Wang X, Hu R, Lin F, Yang T, Lu Y, Sun Z, Li T, Chen J. Lactobacillus reuteri or Lactobacillus rhamnosus GG intervention facilitates gut barrier function, decreases corticosterone and ameliorates social behavior in LPS-exposed offspring. Food Res Int. 2024; 197(Pt 1): 115212.

Probiotic therapy with Lactobacillus reuteri and Lactobacillus rhamnosus (LGG) demonstrates potential as an adjunctive treatment for autism spectrum disorder (ASD). In a rat model of ASD induced by lipopolysaccharide (LPS) injection during pregnancy, we evaluated the effects of these probiotics on offspring. Administration of L. reuteri or LGG for three weeks post-birth improved social deficits and reduced anxiety in LPS-exposed rats. Additionally, probiotics significantly modified short-chain fatty acid profiles, increasing butyric acid levels and decreasing propionic acid levels. They also enhanced colonic barrier integrity by upregulating tight junction proteins, including ZO-1, Occludin, and Claudin4. RNA sequencing identified differential gene expression in pathways related to inflammation, the HPA axis, and reactive oxygen species metabolism, with NADPH oxidase 1 (NOX1) emerging as a crucial gene. Validation studies confirmed that Lactobacillus strains reduced inflammatory cytokines, inhibited corticosterone secretion, increased antioxidant levels, and suppressed the NF-κB/NOX1 pathway. In an H(2)O(2)-induced oxidative stress model using Caco-2 cells, pre-treatment with L. reuteri, LGG, or NF-κB inhibitors enhanced cellular antioxidants, inhibited NF-κB/NOX1 activation, and improved barrier function. Overall, L. reuteri and LGG administration improved social behavior, bolstered colonic barrier function, and mitigated HPA axis overactivation in LPS-exposed rats, while also alleviating oxidative stress in the colon and Caco-2 cells. These findings suggest that L. reuteri and LGG have substantial clinical potential for ASD treatment by targeting multiple pathophysiological mechanisms, including inflammation, HPA axis dysregulation, and oxidative stress, thereby presenting a promising adjunctive therapeutic strategy for enhancing social behavior and gut health in ASD.

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45. Wertheimer O, Hart Y. Autism spectrum disorder variation as a computational trade-off via dynamic range of neuronal population responses. Nat Neurosci. 2024.

Individuals diagnosed with autism spectrum disorder (ASD) show neural and behavioral characteristics differing from the neurotypical population. This may stem from a computational principle that relates inference and computational dynamics to the dynamic range of neuronal population responses, reflecting the signal levels for which the system is responsive. In the present study, we showed that an increased dynamic range (IDR), indicating a gradual response of a neuronal population to changes in input, accounts for neural and behavioral variations in individuals diagnosed with ASD across diverse tasks. We validated the model with data from finger-tapping synchronization, orientation reproduction and global motion coherence tasks. We suggested that increased heterogeneity in the half-activation point of individual neurons may be the biological mechanism underlying the IDR in ASD. Taken together, this model provides a proof of concept for a new computational principle that may account for ASD and generates new testable and distinct predictions regarding its behavioral, neural and biological foundations.

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46. Yasunaga M, Higuchi R, Kusunoki K, Mori C, Mochizuki N. Associations Between DCD Traits, Perceived Difficulties Related to ADHD, ASD, and Reading and Writing Support Needs Among Students in Higher Education: A Pilot Study. Brain Sci. 2024; 14(11).

Background/Objectives: Since the Act for Eliminating Discrimination against Persons with Disabilities was enacted in 2016, the number of students with disabilities in higher education institutions has increased significantly, creating a greater need for support. Developmental Coordination Disorder (DCD) often coexists with other neurodevelopmental disorders such as Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and reading and writing difficulties; yet, awareness of DCD remains low. This study aimed to investigate the prevalence of DCD traits among Japanese higher education students and their relationship with ADHD, ASD, and reading and writing support needs Methods: A pilot study was conducted with 77 university students (mean age: 19.17 ± 0.68) in the Kansai region, using the Adolescents and Adults Coordination Questionnaire (AAC-Q) to screen for DCD traits, along with a questionnaire assessing difficulties related to ADHD and ASD, and a survey on reading and writing support needs. Results: The study found that 12.9% of students scored more than 1 standard deviation above the mean on the AAC-Q. Students in the DCD trait group (n = 10) reported greater difficulties related to ADHD and ASD than those in the non-DCD group (n = 67). Correlation analysis revealed a moderate-to-strong association between AAC-Q scores and difficulties related to ADHD and ASD among students in the DCD trait group. Conclusions: This study suggests the need to raise awareness about DCD traits and to provide comprehensive support for students with ADHD and ASD in Japanese higher education institutions.

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47. Yazdi SA, Janghorbani A, Maleki A. Diagnosis of Autism in Children Based on their Gait Pattern and Movement Signs Using the Kinect Sensor. J Med Signals Sens. 2024; 14: 29.

BACKGROUND: Autism spectrum disorders are a type of developmental disorder that primarily disrupt social interactions and communications. Autism has no treatment, but early diagnosis of it is crucial to reduce these effects. The incidence of autism is represented in repetitive patterns of children’s motion. When walking, these children tighten their muscles and cannot control and maintain their body position. Autism is not only a mental health disorder but also a movement disorder. METHOD: This study aims to identify autistic children based on data recorded from their gait patterns using a Kinect sensor. The database used in this study comprises walking information, such as joint positions and angles between joints, of 50 autistic and 50 healthy children. Two groups of features were extracted from the Kinect data in this study. The first one was statistical features of joints’ position and angles between joints. The second group was the features based on medical knowledge about autistic children’s behaviors. Then, extracted features were evaluated through statistical tests, and optimal features were selected. Finally, these selected features were classified by naïve Bayes, support vector machine, k-nearest neighbors, and ensemble classifier. RESULTS: The highest classification accuracy for medical knowledge-based features was 87% with 86% sensitivity and 88% specificity using an ensemble classifier; for statistical features, 84% of accuracy was obtained with 86% sensitivity and 82% specificity using naïve Bayes. CONCLUSION: The dimension of the resulted feature vector based on autistic children’s medical knowledge was 16, with an accuracy of 87%, showing the superiority of these features compared to 42 statistical features.

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