Autism Spectrum Disorder Patients Research Articles

A short investigation of the effect of the selection of human brain atlases on the performance of ASD's classification models

This study investigated the impact of brain atlas selection on the classification accuracy of Autism Spectrum Disorder (ASD) models using functional Magnetic Resonance Imaging (fMRI) data. Brain atlases, such as AAL, CC200, Harvard-Oxford, and Yeo 7/17, are used to define regions of interest (ROIs) for fMRI analysis and play a crucial role in enabling researchers to study connectivity patterns and neural dynamics in ASD patients. Through a systematic review, we examined the performance of different atlases in various machine-learning and deep-learning frameworks for ASD classification. The results reveal that atlas selection significantly affects classification accuracy, with denser atlases, such as CC400, providing higher granularity, whereas coarser atlases such as AAL, offer computational efficiency. Furthermore, we discuss the dynamics of combining multiple atlases to enhance feature extraction and explore the implications of atlas selection across diverse datasets. Our findings emphasize the need for standardized approaches to atlas selection and highlight future research directions, including the integration of novel atlases, advanced data augmentation techniques, and end-to-end deep-learning models. This study provides valuable insights into optimizing fMRI-based ASD diagnosis and underscores the importance of interpreting atlas-specific features for an improved understanding of brain connectivity in ASD.

The value of hippocampal sub-region imaging features for the diagnosis and severity grading of ASD in children

BackgroundHippocampal structural changes in Autism Spectrum Disorder (ASD) are inconsistent. This study investigates hippocampal subregion changes in ASD patients to reveal intrinsic hippocampal anomalies. MethodsA retrospective study from Hainan Children’s Hospital database (2020–2023) included ASD patients and matched controls. We classified ASD participants based on severity, dividing all subjects into four groups: normal, mild, moderate, and severe. High-resolution T1-weighted MRI images were analyzed for hippocampal subregion segmentation and volume calculations using Freesurfer. Texture features were extracted via the Gray-Level Co-occurrence Matrix. The Receiver Operating Characteristic curve was used to evaluate seven random forest predictive models constructed from volume, subregion, and texture features, as well as their combinations following feature selection. ResultsThe study included 114 ASD patients (98 boys, 2–8 years; 16 girls, 2–6 years; 17 mild, 57 moderate, 40 severe) and 111 healthy controls (HCs). No significant differences in volumes were found between ASD patients and HCs (adjusted P-value >0.05). The seven random forest models showed that single volume and texture features performed poorly for ASD classification; however, integrating various feature types improved AUC values. Further selection of texture, subregion, and volume features enhanced AUC performance across normal and varying severity categories, demonstrating the potential value of specific subregions and integrated features in ASD diagnosis. ConclusionRandom forest models revealed that hippocampal volume, texture features, and subregion characteristics are crucial for diagnosing and assessing the severity of ASD. Integrating selected texture and subregion features optimized diagnostic efficacy, while combining texture, subregion, and volume features further improved severity grading effectiveness.

Optimal dose of oxytocin to improve social impairments and repetitive behaviors in autism spectrum disorders: meta-analysis and dose–response meta-analysis of randomized controlled trials

IntroductionSocial impairments and repetitive behaviors are at the core symptoms of autism spectrum disorder (ASD). Intranasal administration of the neuropeptide oxytocin (OXT) is a promising treatment. However, there have been inconsistencies in the effects of OXT on social impairments and repetitive behaviors.MethodsA comprehensive search in PubMed, the Cochrane Library, Embase, and Web of Science was conducted to gather randomized controlled trials (RCTs) on the efficacy of OXT in patients diagnosed with ASD up to 11/06/2024. The core outcomes were social impairments measured by total Social Responsiveness Scale (SRS) scores and repetitive behaviors measured by the Repetitive Behavior Scale (RBS).ResultsThis meta-analysis ultimately included 12 RCTs with 498 ASD patients. In an initial analysis, intranasal OXT showed no significant effect on social impairments. For a high dose of 48 IU per day, a beneficial effect on social impairments was found. According to the dose–response meta-analysis, the results indicated that higher doses of OXT might be more effective for social impairments. Depending on repetitive behaviors, the overall analysis showed no significant effect, while the dose over 48 IU per day revealed significant results and the dose–response meta-analysis suggested that higher doses could be more effective for repetitive behaviors.DiscussionAlthough these findings show no consistent beneficial effects, the results of the dose–response meta-analysis suggest that high doses of intranasal OXT per day may be more effective in ASD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42024567213.

Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence. The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software. Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = -0.48; 95% CI = -0.66- -0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = -1.15; 95% CI = -2.01- -0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03-1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13-0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21-1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521-0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis. TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.

Glycosylation Pathways Targeted by Deregulated miRNAs in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a complex condition with a multifactorial aetiology including both genetic and epigenetic factors. MicroRNAs (miRNAs) play a role in ASD and may influence metabolic pathways. Glycosylation (the glycoconjugate synthesis pathway) is a necessary process for the optimal development of the central nervous system (CNS). Congenital Disorders of Glycosylation (CDGs) (CDGs) are linked to over 180 genes and are predominantly associated with neurodevelopmental disorders (NDDs) including ASD. From a literature search, we considered 64 miRNAs consistently deregulated in ASD patients (ASD-miRNAs). Computational tools, including DIANA-miRPath v3.0 and TarBase v8, were employed to investigate the potential involvement of ASD-miRNAs in glycosylation pathways. A regulatory network constructed through miRNet 2.0 revealed the involvement of these miRNAs in targeting genes linked to glycosylation. Protein functions were further validated through the Human Protein Atlas. A total of twenty-five ASD-miRNAs were identified, including nine miRNAs that were differentially expressed in cells or brain tissue in ASD patients and associated with glycosylation pathways, specifically protein N- and O-glycosylation and glycosaminoglycan biosynthesis (heparan sulfate). A number of CDG genes and/or ASD-risk genes, including DOLK, GALNT2, and EXT1, were identified as targets, along with validated interactions involving four key miRNAs (hsa-miR-423-5p, hsa-miR-30c-5p, hsa-miR-195-5p, and hsa-miR-132-5p). B4GALT1, an ASD susceptibility gene, emerged as a central regulatory hub, reinforcing the link between glycosylation and ASD. In sum, the evidence presented here supports the hypothesis that ASD-miRNAs mediate the epigenetic regulation of glycosylation, thus unveiling possible novel patho-mechanisms underlying ASD.

The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder.

Sensory processing abnormalities have been noted since the first clinical description of autism in 1940. However, it was not until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 that sensory challenges were considered as symptoms of autism spectrum disorder (ASD). Multisensory processing is of paramount importance in building a perceptual and cognitive representation of reality. For this reason, deficits in multisensory integration may be a characteristic of ASD. The neurohormone oxytocin (Oxt) is involved in the etiology of ASD, and there are several ongoing clinical trials regarding Oxt administration in ASD patients. Recent studies indicate that Oxt triggers muscle contraction modulating thermogenesis, while abnormal thermoregulation results in sensory deficits, as in ASD. Activation of the Oxt system through exposure to cold stress regulates the expression of oxytocin receptor (Oxtr) in the brain and circulating Oxt, and if this mechanism is pathologically disrupted, it can lead to sensory processing abnormalities since Oxt acts as a master gene that regulates thermogenesis. This review will describe the sensory deficits characteristic of ASD together with the recent theories regarding how the modulation of Oxt/Oxtr in the brain influences sensory processing in ASD.

Different faces of autism: Patients with mutations in PTEN and FMR1 genes.

Autism spectrum disorder (ASD) is among the most common neurodevelopmental conditions in humans. While public awareness of the challenges faced by individuals with autism is steadily increasing, the underlying causes of abnormalities observed in ASD remains incompletely understood. The autism spectrum is notably broad, with symptoms that can manifest in various forms and degrees of severity. Core features of ASD, such as communication difficulties, impaired social interactions, and restricted patterns of behavior, interests, and activities, are often accompanied by other co‑occurring conditions, such as anxiety. ASD affects individuals regardless of gender, race, or ethnicity. Although we are currently unable to pinpoint a single definitive cause of autism, it is clear that genetics play a crucial role in its development. The first genes associated with an increased risk for ASD were discovered in rare monogenic disorders, such as fragile X syndrome (FXS), caused by mutations in the fragile X messenger ribonucleoprotein 1 (FMR1) gene, and macrocephaly, linked to mutations in the phosphatase and tensin homolog (PTEN) gene. This review aims to summarize the current knowledge of ASD in patients with mutations in the FMR1 and PTEN genes.

Exploring the neurotoxic effects of microbial metabolites: A potential link between p-Cresol and autism spectrum disorders?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex etiology, including genetic and environmental factors. A growing body of evidence (preclinical and clinical studies) implicates a potential role of gut microbiome dysregulation in ASD pathophysiology. This review focuses on the microbial metabolite p-Cresol, produced by certain gut bacteria such as Clostridium, and its potential role in ASD. The review summarizes studies investigating the gut microbiome composition in ASD patients, particularly the increased abundance of Clostridium species and associated gastrointestinal symptoms. The potential neurotoxic effects of p-Cresol are explored, including its influence on neurotransmitter metabolism (especially dopamine), neuroinflammation, and brain development. The mechanistic findings from the preclinical studies of p-Cresol's induction of ASD-like behaviors and its impact on the dopaminergic system are discussed. Literature studies indicated increased levels of p-Cresol in the urine of patients with ASD. This increasing evidence suggests that p-Cresol may serve as a crucial biomarker for understanding the relationship between gut microbiota and ASD, opening avenues for potential diagnostic and therapeutic interventions.

Chronobiology in Paediatric Neurological and Neuropsychiatric Disorders: Harmonizing Care with Biological Clocks.

Background: Chronobiology has gained attention in the context of paediatric neurological and neuropsychiatric disorders, including migraine, epilepsy, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Disruptions in circadian rhythms are associated with key symptoms such as sleep disturbances, mood dysregulation, and cognitive impairments, suggesting a potential for chronobiology-based therapeutic approaches. Methods: This narrative review employs a systematic approach to identify relevant studies through searches of three major scientific databases, NCBI/PubMed, ScienceDirect, and Scopus, up to July 2024. We used a combination of broad and condition-specific keywords, such as "chronobiology", "biorhythm", "pediatric", "epilepsy", "ADHD", and "ASD", among others. Articles in English that focused on clinical features, treatments, or outcomes related to circadian rhythms in paediatric populations were included, while non-peer-reviewed articles and studies lacking original data were excluded. Rayyan software was used for article screening, removing duplicates, and facilitating consensus among independent reviewers. Results: A total of 87 studies were included in the analysis. Findings reveal a consistent pattern of circadian rhythm disruptions across the disorders examined. Specifically, dysregulation of melatonin and cortisol secretion is observed in children with ASD, ADHD, and PTSD, with altered circadian timing contributing to sleep disturbances and mood swings. Alterations in core clock genes (CLOCK, BMAL1, PER, and CRY) were also noted in children with epilepsy, which was linked to seizure frequency and timing. Chronotherapy approaches showed promise in managing these disruptions: melatonin supplementation improved sleep quality and reduced ADHD symptoms in some children, while light therapy proved effective in stabilizing sleep-wake cycles in ASD and ADHD patients. Additionally, behaviour-based interventions, such as the Early Start Denver Model, showed success in improving circadian alignment in children with ASD. Conclusions: This review highlights the significant role of circadian rhythm disruptions in paediatric neurological and neuropsychiatric disorders, with direct implications for treatment. Chronobiology-based interventions, such as melatonin therapy, light exposure, and individualized behavioural therapies, offer potential for improving symptomatology and overall functioning. The integration of chronotherapy into clinical practice could provide a paradigm shift from symptom management to more targeted, rhythm-based treatments. Future research should focus on understanding the molecular mechanisms behind circadian disruptions in these disorders and exploring personalized chronotherapeutic approaches tailored to individual circadian patterns.

Effects of Massage on Self-regulatory Difficulties, Tactile and Oral Abnormalities, and Parenting Stress in Children with Autism Spectrum Disorder (ASD): A Systematic Review and Meta-analysis.

The Centers for Disease Control and Prevention stated that about 1 in every 44 children between the ages of 4 and 8 years old had been identified with autism spectrum disorder (ASD). Complementary interventions such as massage are crucial for the improvement of the health outcomes of ASD patients, such as abnormal sensory response; Autism Behavior Checklist; parenting stress, self-regulatory difficulties, social, language, and communication abilities; tactile or oral abnormalities; Vineland daily living skills; Vineland socialization; Childhood Autism Rating Scale; Preschool Language Scale 5th Edition (PLS-5) auditory communication; and PLS-5 expressive communication. We aim to systematically investigate the effects of different types of massage on self-regulatory difficulties, tactile and oral abnormalities, and parenting stress in children with ASD. PubMed, Cochrane Library, Scopus, and Web of Science were scoured from their inception through November 15, 2022. Research comparing massage efficacy in children with ASD to other methods or a control group was included. For randomized controlled trials (RCTs), we utilized the Cochrane risk of bias tool; and for cohort studies, we used the tool developed by the National Institutes of Health. Meta-analysis was carried out with Review Manager 5.4. For our continuous data, we calculated the mean difference (MD) and 95% confidence interval (95% CI). We included 10 studies with a total number of 485 children with autism. Our analysis showed a significant decrease in the massage group regarding self-regulatory difficulties (MD = -9.15; 95% CI (-13.69 to -4.60), p < 0.0001). Also, the massage group showed a significant decrease in tactile or oral abnormalities compared with the control group (MD = -4.83; 95% CI (-7.86 to -1.80), p = 0.002). Moreover, parenting stress significantly decreased in the massage group compared to the control group (MD = -4.31; 95% CI (-7.02 to -1.61), p = 0.002). Qigong and traditional Thai massage improved self-regulatory difficulties and decreased tactile or oral abnormalities in children with autism. Moreover, they decreased parenting stress. However, we need more RCTs with larger sample sizes with high quality to assess the different types of massage effects on autistic children and produce more valid results. So, Qigong and traditional Thai massage could be used as a complement to educational and training interventions in children with autism.

Exploring congenital sucrase-isomaltase deficiency in autism spectrum disorder patients with irritable bowel syndrome symptoms: A prospective SI gene sequencing study.

Congenital sucrase-isomaltase deficiency (CSID) is an inherited metabolic disorder causing chronic gastrointestinal symptoms and malnutrition when untreated. Most CSID patients are likely to remain under- or misdiagnosed. This study aimed to investigate prevalence of CSID among patients with autism spectrum disorder (ASD) presenting with irritable bowel syndrome (IBS) symptoms via prospective SI gene sequencing. A prospective cross-sectional study was conducted on 98 ASD patients exhibiting gastrointestinal symptoms consistent with IBS. Participants were assessed according to Rome IV criteria and underwent SI gene sequencing. Demographic, clinical, and dietary data were collected and analyzed. Sucrose content in various fruits and vegetables was evaluated using three-day food record, and gastrointestinal symptoms were rated on Likert scale. Seven patients (7%) were diagnosed with CSID based on SI gene analysis, revealing six different variants, including four novel mutations. One patient was homozygous for one variant, and six patients were heterozygous. Clinical presentations predominantly included diarrhea, abdominal pain, and bloating, with two patients showing growth retardation. One patient was diagnosed in adulthood. Food allergy and lactose intolerance were the misdiagnoses prior to CSID diagnosis in two patients. Real prevalence of CSID is likely underestimated. Clinical heterogeneity and non-specific symptoms contribute to diagnostic challenges. Gastrointestinal symptoms consistent with IBS in ASD patients should include CSID in differential diagnosis. Early genetic screening for SI variants in ASD patients with IBS symptoms can facilitate timely diagnosis and management, improving outcomes. Heterozygous variants of the SI gene should also be considered, as heterozygous patients can exhibit typical CSID symptoms.

Therapeutic Role of Nutraceuticals in Ameliorating Neurodevelopmental Disorders: A Focus on Autism Spectrum Disorder (ASD) – State of art Review

Nutraceuticals are beneficial compounds present in foods that act as therapeutic and preventive agents against diseases. By following a diet designed for the diseased condition, the nutraceuticals provide an ameliorating effect. Nutritional foods comprise active components like polyphenols, flavonoids, and alkaloids with unquestionable antioxidant activity. For many disorders, oxidative stress and free radicals are the foremost causes. So, the antioxidant activity of functional foods has the capability to fight against countless physiological defects. The most intricate disorder with an unpredictable, definite cause with a high range of aetiology in infants these days is Autism Spectrum Disorder (ASD). Treatment for ASD is a highly challenging research field for upcoming researchers on the same side. ASD patients also needed an effective treatment without side effects. Then diet-based approaches are the main aim, due to their beneficial effects with less toxicity, to maintain the homeostatic condition of the ASD patients. Foodiceuticals ameliorate the adverse effects of neurodevelopment, neurodegenerative disorders, and other metabolic disorders. The upgrading effects of superfoods like resveratrol, curcumin, crocin, catechin, lycopene, probiotics, melatonin, withaferin, and carotene, etc., are examined in the ASD animal models with varied dosages. However, it showed a better effect in improving ASD behaviour via mediating the genetic alterations. In this review, the detailed mechanisms of pharmaceutical foods are reviewed. The potential therapeutic value of nutraceuticals and functional foods in ASD lies in their antioxidant capability and ability to modulate genetic alterations. Promising such results are reported from foods, such as resveratrol, curcumin, and probiotics in preclinical studies related to ASD behaviours. The results further warrant clinical trials to establish their efficacy and safety. The article highlights their antioxidant activity, ability to modulate genetic alterations, and promising effects in preclinical studies, emphasizing the need for clinical trials to confirm efficacy and safety. Based on the review of nutraceuticals given a clear-cut point in the treatment of ASD, there is a positive result in prevention and treatment not only in ASD but in other diseases too.

Metformin efficacy and safety as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled trial.

Antidiabetic medications have shown efficacy in alleviating autism symptoms. However, there is a lack of clinical research on the impact of metformin on irritability associated with autism. This study aimed to assess the efficacy and safety of metformin as an adjuvant therapy with risperidone for managing irritability in children diagnosed with Autism Spectrum Disorder (ASD). This is a randomized, 10-week, double-blind, placebo-controlled trial conducted at the children's autism clinic of Roozbeh Hospital (Tehran, Iran) from March 2024 to May 2024. Participants were divided into two groups of risperidone plus metformin (500 mg per day) and risperidone plus placebo and were assessed at baseline, weeks 5 and 10 with the aberrant behavior checklist-community scale (ABC-C). A total of 55 patients were included in the final analysis. Irritability (primary outcome measure) sharply decreased in the metformin compared to the placebo group (p = 0.008). Among the other four subscales of ABC-C, the hyperactivity/noncompliance score showed a significant drop during the baseline-to-week-5 period (p = 0.021). In addition, inappropriate speech subscales decreased significantly from baseline-to-week 5 in the metformin compared to the placebo group (p = 0.045). No other significant finding was observed among ABC-C scores for lethargy/social withdrawal or stereotypic behavior subscales. Metformin demonstrated promising results in reducing irritability in ASD patients, which is in concordance with previous studies. However, further studies are required before any broad clinical recommendation.

The intersection of inflammation and DNA damage as a novel axis underlying the pathogenesis of autism spectrum disorders.

Autism spectrum disorders (ASD) affects 1 in 36 children and is characterized by repetitive behaviors and difficulties in social interactions and social communication. The etiology of ASD is extremely heterogeneous, with a large number of ASD cases that are of unknown or complex etiology, which suggests the potential contribution of epigenetic risk factors. In particular, epidemiological and animal model studies suggest that inflammation during pregnancy could lead to an increased risk of ASD in the offspring. However, the molecular mechanisms that contribute to ASD pathogenesis in relation to maternal inflammation during pregnancy in humans are underexplored. Several pro-inflammatory cytokines have been associated with increased autistic-like behaviors in animal models of maternal immune activation, including IL-17A. Using a combination of ASD patient lymphocytes and stem cell-derived human neurons exposed to IL-17A we discovered a shared molecular signature that highlights a metabolic and translational node that could lead to altered neuronal excitability. Further, our work on human neurons brings forward the possibility that defects in the DNA damage response could be underlying the effect of IL-17A on human excitatory neurons, linking exacerbated unrepaired DNA damage to the pathogenicity of maternal inflammation in connection to ASD.

The Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition mainly characterized by both a scarce aptitude for social interactions or communication and engagement in repetitive behaviors. These primary symptoms can manifest with variable severity and are often paired with a heterogeneous plethora of secondary complications, among which include anxiety, ADHD (attention deficit hyperactivity disorder), cognitive impairment, sleep disorders, sensory alterations, and gastrointestinal issues. So far, no treatment for the core symptoms of ASD has yielded satisfactory results in a clinical setting. Consequently, medical and psychological support for ASD patients has focused on improving quality of life and treating secondary complications. Despite no single cause being identified for the onset and development of ASD, many genetic mutations and risk factors, such as maternal age, fetal exposure to certain drugs, or infections have been linked to the disorder. In preclinical contexts, these correlations have acted as a valuable basis for the development of various murine models that have successfully mimicked ASD-like symptoms and complications. This review aims to summarize the findings of the extensive literature regarding the pharmacological and nutraceutical interventions that have been tested in the main animal models for ASD, and their effects on core symptoms and the anatomical, physiological, or molecular markers of the disorder.

Research advances in gut microbes and autism spectrum disorders

This paper concludes that recent research on the interrelationship between gut microbiota and autism spectrum disorder (ASD) has gained significant attention. The study found that the composition of the gut microbiota in ASD patients is often markedly different from that of the general population, particularly in the species and abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, which are frequently imbalanced. The imbalance in intestinal microorganisms not only affects gut health but also disrupts the neurological functions mediated by the gut-brain axis, exacerbating the behavioral and cognitive symptoms associated with ASD. In recent years, microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), have shown some promise. The use of probiotics and prebiotics can increase the proportion of beneficial flora in the gut of patients with ASD, helping to produce anti-inflammatory short-chain fatty acids, thereby improving neurological symptoms. Additionally, FMT, which involves transplanting gut microbes from healthy individuals into ASD patients, has demonstrated significant improvements in both gut and behavioral symptoms in several studies. However, due to the high individual variability among ASD patients, a single microbial intervention is not consistently effective across all individuals. Some patients respond well to probiotics or FMT, whereas others show limited symptom improvement. This variability may be attributed to each patient's unique microbiota composition, immune status, and metabolic profile. Therefore, further research is needed to identify biomarkers that can predict the effectiveness of microbial interventions, thereby enabling more precise and individualised therapies. This review aims to provide guidance for future research and to offer a theoretical foundation and data support for exploring microbial modulation as a potential treatment for ASD.

Lithium normalizes ASD-related neuronal, synaptic, and behavioral phenotypes in DYRK1A-knockin mice.

Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays, intellectual disability (ID) and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice reportedly leads to ASD-related phenotypes. However, the key pathological mechanisms remain unclear and human DYRK1A mutations remain uncharacterized in mice. Here, we generated and studied Dyrk1a-knockin mice carrying a human ASD patient mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteomic patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues the brain volume, behavior, dendritic, synaptic, and signaling/synapse phospho-proteomic phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to the phenotypic alterations seen in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects in preventing juvenile and adult-stage phenotypes.

Systemic heterogeneity in autism spectrum disorder revealed by individualized structural covariance network analysis.

Autism spectrum disorder (ASD) is clinically heterogeneous, and resent neuroimaging studies have shown the presence of brain structural heterogeneity in ASD. However, there is currently a lack of evidence for systemic level brain structural heterogeneity. This study aimed to reveal the heterogeneity of brain structural changes at the systemic level in ASD patients through individual differential structural covariance network (IDSCN) analysis. We included 803 neurotypical controls (NCs) and 650 ASD patients from 24 sites and the corresponding structural magnetic resonance and clinical data. 516 ASD patients were used as training group, and 134 ASD patients were selected as an independent validation group. In the training group, we constructed IDSCN for each ASD patient, identified differentiated structural covariance edges, and resolved systemic heterogeneity using K-means clustering algorithm. We then conducted statistical analyses on the demographical and clinical data of the ASD subgroups, and performed correlation analyses between structural covariance edges and clinical profiles within each ASD subgroup. We also tested the reliability of the IDSCN in the validation group. The results of the training and validation groups were similar, revealing two subtypes of ASD, with 17 brain connections showing differences between the two subtypes. There were differences in clinical profiles between the two subgroups in restricted repetitive behavior score from autism diagnostic interview-revised (ADI_RRB_TOTAL), total score of autism diagnostic observation schedule (ADOS), social interaction score from ADOS and stereotyped behaviors score from ADOS. In both datasets, we also found a significant correlation between ADI_RRB_TOTAL scale and the Z-score for edges between the bilateral ventral tegmental area (VTA) and between the left VTA and right substantia nigra pars compacta. ASD exhibited brain structural heterogeneity at the systemic level, mainly involving nucleus in the subcortical regions and brainstem, which can affect RRB in ASD patients. The two subtypes discovered in this study have the potential to be applied in precise diagnosis and treatment of the disorder.

O PAPEL DA ENFERMAGEM NA ASSISTÊNCIA AOS PACIENTES AUTISTAS ADULTOS

Autism Spectrum Disorder (ASD) is recognized as a condition characterized by difficulties in social interaction and atypical behaviors. In Brazil, the diagnosis of ASD has increased, reflecting greater awareness, and it is generally addressed in children but also affects adults. The main objective is to succinctly and clearly address the importance of nursing in the care of adult autistic patients. This research is a descriptive bibliographic review of four scientific articles, after applying descriptors using the PRISMA flowchart. Despite the challenges encountered, such as the lack of training to deal with ASD patients, the studies highlight the relevance of individualized care for autistic adults and underscore the importance of nursing for

Increased Risk of Dentoalveolar Trauma in Patients with Autism Spectrum Disorder: A Systematic Review with Meta-Analysis.

The prevalence of traumatic dental injuries (TDI) in patients with autism spectrum disorders (ASD) remains unclear. Given these discrepancies, an updated review of the evidence on the risk of TDI in patients with ASD is essential. This systematic review and meta-analysis aimed to evaluate the prevalence of TDI in patients with ASD and compare it to that in neurotypical patients. This study protocol was registered on PROSPERO (CRD42024580127) and followed the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. A comprehensive search of four databases-MEDLINE/PubMed, Web of Science, Scopus, and Embase-was conducted for articles published up to August 2024. Moreover, the gray literature (ProQuest) and reference lists were screened. The inclusion criteria required participants with ASD to assess TDI across deciduous, mixed, and permanent dentition regardless of age. No restrictions were applied on TDI type, language, or publication date. Additionally, case reports, reviews, letters, and studies addressing other oral disorders without specific TDI data were excluded. A single-arm meta-analysis evaluated the cumulative proportion and 95% confidence interval (CI) of TDI in patients with ASD. Moreover, a comparative meta-analysis was performed to assess the risk of TDI between ASD and neurotypical patients, calculating the odds ratio (OR) with a 95% CI, and a p < 0.05 was deemed significant, using the R program. Quality assessment was performed using the National Heart, Lung, and Blood Institute tool, and the certainty of evidence was evaluated using GRADE. A total of 22 studies were included to determine the overall prevalence of TDI, of which 16 studies directly compared patients with ASD to neurotypical individuals. In total, 3817 participants were evaluated, including 2162 individuals with ASD and 1655 neurotypical patients. A single-arm meta-analysis estimated a TDI prevalence of 22% (Confidence Interval [CI]: 17-27%) among patients with ASD. A significant difference in the risk was observed between ASD and neurotypical patients (p = 0.003; Odds Ratio [OR]: 1.67; CI: 1.19-2.26). However, substantial heterogeneity was observed in this analysis. Although the majority of studies were rated as high quality, the certainty of the evidence was considered very low. Despite the limitations of this study, the findings suggest that patients with ASD are at a higher risk of developing TDI than the risk observed in neurotypical patients. Therefore, preventive educational initiatives are recommended to reduce the risk of TDI in this population.