Autism spectrum disorder (ASD) is a behaviorally defined complex neurodevelopmental syndrome characterized by persistent social communication and interaction deficit. Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms. Several reviews have been published regarding TMS-based ASD treatment, however, a systematic review on study characteristics, specific stimulating parameters, localization techniques, stimulated targets, behavioral outcomes, and neuroimage biomarker changes is lagged behind since 2018. Here, we performed a systematic search on literatures published after 2018 in PubMed, Web of Science, and Science Direct. After screening, the final systematic review included 17 articles, composing seven randomized controlled trial studies and ten open-label studies. Two studies are double-blind, while the other studies have a moderate to high risk of bias attributing to inadequate subject- and evaluator-blinding to treatment allocation. Five studies utilize theta-burst stimulation mode, and the others apply repetitive TMS with low frequency (five studies), high frequency (six studies), and combined low and high frequency stimulation (one study). Most researchers prioritize the bilateral dorsolateral prefrontal lobe as stimulation target, while parietal lobule, inferior parietal lobule, and posterior superior temporal sulci have also emerged as new targets of attention. One third of the studies use neuronavigation based on anatomical magnetic resonance imaging to locate the stimulation target. After TMS intervention, discernible enhancements across a spectrum of scales are evident in stereotyped behavior, repetitive behavior, and verbal social domains. A comprehensive review of literature spanning the last five years demonstrates the potential of TMS treatment for ASD in ameliorating the clinical core symptoms.

Our core premise is that personalized variations of a ketogenic diet are likely to benefit pediatric patients with neuropsychiatric symptoms across multiple domains. Although pediatric epilepsy is currently a well-accepted indication for a strict ketogenic diet, there is a dearth of knowledge and therefore clinical guidelines upon which to recommend nutritional ketosis for pervasive pediatric conditions such as autism spectrum disorder and ADHD, even when comorbid epilepsy is present. However, there are published cohort studies and current clinical trials implementing medical ketogenic therapies for cognitive impairment, psychiatric comorbidities, motor disability, and even neuroinflammation. As holistic practitioners, it is imperative that we consider the health of a child in its entirety - and additionally offer the ketogenic diet as a therapeutic option when it may be synergistic in treating extra-neurologic diseases such as obesity. While there are uniquely pediatric potential adverse side effects such as linear growth deceleration and micronutrient deficiencies, previous trials in epilepsy and our center\'s experience have already proven the ketogenic diet to be a low-risk intervention when optimized with appropriate patient monitoring and support.

(1) Background and Objectives: This review aims to identify the latest literature on the possible effect of bilingualism on the linguistic skills of children with autism spectrum disorder (ASD) residing in Greece. (2) Materials and Methods: The literature was searched in the databases of Scopus and PubMed by selecting articles and by reviewing four studies published in peer-reviewed journals. This Scoping Review is based on the standards of PRISMA recommendations for scoping reviews, while the PCC framework was used as a guide to construct clear and meaningful objectives and eligibility criteria. (3) Results: The publications included in the review addressed a variety of language-related skills, including morphology, the syntax-pragmatics interface, narrative ability, as well as both receptive and expressive language skills. (4) Conclusions: Three out of four studies provide evidence that bilingual ASD children are not disadvantaged compared to monolingual peers but rather enjoy some benefits, to a certain extent, due to bilingualism. However, the number of the reviewed studies as well as the limitations of the studies themselves render this conclusion tentative. Additionally, the findings set guidelines that speech therapists, educators, psychologists, and doctors in the Greek context need to follow when treating or educating bilingual children with ASD.

This study addressed the harmful effects of artificial colors in pediatric populations, including children diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), as well as those without behavioral disorders. There is a consensus that synthetic food colorings have several impacts on consumers, especially pediatrics, due to their influence on sensory appeal, which can encourage preference for certain foods. The results revealed that these color additives are directly linked to a series of health problems, with a greater impact on children, including a predisposition to pathological conditions such as carcinogenic, allergenic, mutagenic, cytotoxic, and clastogenic activities, as well as gastrointestinal and respiratory problems, in addition to behavioral changes in children with and without diagnosed disorders. The harms of synthetic dyes in children with or without comorbidities are worrying and require a careful and proactive approach from parents, caregivers and public authorities.

BACKGROUND: In addition to the inherent challenges of their condition, children with autism spectrum disorder (ASD) are also susceptible to the global obesity epidemic. However, concerning the prevalence of obesity within the Moroccan ASD pediatric population, data remain scarce.
METHODS: A total of 258 children (boys = 195) aged 6 to 12 years old (mean = 9.4 ± 1.4) diagnosed with ASD participated in this study. Besides the body mass and height, four significant anthropometric markers for assessing obesity were examined: body mass index (BMI), body surface area (BSA), waist circumference (WC), and waist-to-height ratio (WHtR). Each anthropometric marker was categorized into one of three cardiometabolic risk levels based on the Z-scores and their corresponding percentiles. The distribution was as follows: low risk (≤84th percentile), high risk (85th-94th percentile), and very high risk (≥95th percentile). Subsequently, a multiple regression analysis was employed to develop an algorithm that generates a composite risk score. This score incorporates all the anthropometric variables simultaneously, while also weighting their individual contributions to the cardiometabolic risk.
RESULTS: Children with ASD exhibit an anthropometric profile that markedly increases their susceptibility to cardiometabolic issues. While roughly 11% of the general Moroccan child population is overweight or obese, this figure soars to nearly 60% among children with ASD when considering the central adiposity markers. Furthermore, children from middle-class socioeconomic backgrounds display a more than threefold greater risk of developing overweight or obesity compared to their counterparts from lower socioeconomic backgrounds.
CONCLUSIONS: This study has, for the first time, provided an up-to-date overview of the cardiometabolic risk in Moroccan children with ASD using traditional anthropometric measurements. The primary risk factor is clearly linked to central (abdominal) adiposity, which is recognized as the most deleterious. This study highlights the need to include general and central obesity markers. This study underscores the importance of incorporating both general and central adiposity markers for a more comprehensive assessment, and it emphasizes the need for closer monitoring within this high-risk population.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Oxidative stress may be a critical link between mitochondrial dysfunction and ASD as reactive oxygen species (ROS) generated from pro-oxidant environmental toxicants and activated immune cells can result in mitochondrial failure. Recently, mitochondrial dysfunction, autoimmunity, and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention.
METHODS: The relationship between lipid mediator markers linked to inflammation induction, such as phospholipase A2/cyclooxygenase-2 (PLA2/Cox-2), and the mitochondrial dysfunction marker anti-mitochondrial antibodies (AMA-M2), and anti-histone autoantibodies in the etiology of ASD was investigated in this study using combined receiver operating characteristic (ROC) curve analyses. This study also sought to identify the linear combination for a given set of markers that optimizes the partial area under ROC curves. This study included 40 age- and sex-matched controls and 40 ASD youngsters. The plasma of both groups was tested for PLA2/COX-2, AMA-M2, and anti-histone autoantibodies\' levels using ELISA kits. ROC curves and logistic regression models were used in the statistical analysis.
RESULTS: Using the integrated ROC curve analysis, a notable rise in the area under the curve was noticed. Additionally, the combined markers had markedly improved specificity and sensitivity.
CONCLUSIONS: The current study suggested that measuring the predictive value of selected biomarkers related to mitochondrial dysfunction, autoimmunity, and lipid metabolism in children with ASD using a ROC curve analysis could lead to a better understanding of the etiological mechanism of ASD as well as its relationship with metabolism.

The prevalence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasing, with a tendency for co-occurrence. Some studies indicate a connection between atypical sensory processing and executive function. This study aims to explore the distinctive etiology of executive function deficits in children with ASD+ADHD by investigating the relationship between sensory processing and executive function, comparing children with ASD, ASD+ADHD, ADHD, and typically developing children (TD).
METHODS: Sensory Profile 2 (SP-2) and Behavior Rating Inventory of Executive Function 2 (BRIEF-2) were measured in 120 school-aged children. The results of the above scales were compared across these four groups, and correlation and regression analyses between BRIEF2 and SP2 were conducted.
RESULTS: Our research revealed varying levels of atypical sensory processing and executive function anomalies across the three neurodevelopmental disorder groups compared to the TD group. The ASD+ADHD group showed particularly significant differences. The heightened emotional problems observed in ASD+ADHD children may be associated with more prominent atypical sensory processing. Variance analysis of inhibitory function revealed differences between ASD+ADHD and ADHD children, suggesting distinct etiological mechanisms for attention issues between ASD+ADHD and ADHD.
CONCLUSIONS: ASD+ADHD represents a phenotype distinct from both ASD and ADHD. Special consideration should be given to interventions for children with ASD+ADHD. The results of this study may offer a new perspective on understanding the occurrence of ASD+ADHD and potential individualized intervention methods.

This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on identifying potential differences in gut bacteria between these groups. The microbiota was analyzed through the massive sequencing of region V3-V4 of the 16S RNA gene, utilizing DNA extracted from stool samples of participants. Our findings revealed no significant differences in the dominant bacterial phyla (Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Verrucomicrobiota) between the ASD and NT groups. However, at the genus level, notable disparities were observed in the abundance of Blautia, Prevotella, Clostridium XI, and Clostridium XVIII, all of which have been previously associated with ASD. Furthermore, a sex-based analysis unveiled additional discrepancies in gut microbiota composition. Specifically, three genera (Megamonas, Oscilibacter, Acidaminococcus) exhibited variations between male and female groups in both ASD and NT cohorts. Particularly noteworthy was the exclusive presence of Megamonas in females with ASD. Analysis of predicted metabolic pathways suggested an enrichment of pathways related to amine and polyamine degradation, as well as amino acid degradation in the ASD group. Conversely, pathways implicated in carbohydrate biosynthesis, degradation, and fermentation were found to be underrepresented. Despite the limitations of our study, including a relatively small sample size (30 ASD and 31 NT children) and the utilization of predicted metabolic pathways derived from 16S RNA gene analysis rather than metagenome sequencing, our findings contribute to the growing body of evidence suggesting a potential association between gut microbiota composition and ASD. Future research endeavors should focus on validating these findings with larger sample sizes and exploring the functional significance of these microbial differences in ASD. Additionally, there is a critical need for further investigations to elucidate sex differences in gut microbiota composition and their potential implications for ASD pathology and treatment.

Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.

The prevalence of autism spectrum disorder (ASD) is still increasing, which means that this neurodevelopmental lifelong pathology requires special scientific attention and efforts focused on developing novel therapeutic approaches. It has become increasingly evident that neuroinflammation and dysregulation of neuro-immune cross-talk are specific hallmarks of ASD, offering the possibility to treat these disorders by factors modulating neuro-immunological interactions. Mesenchymal stem cell-based therapy has already been postulated as one of the therapeutic approaches for ASD; however, less is known about the molecular mechanisms of stem cell influence. One of the possibilities, although still underestimated, is the paracrine purinergic activity of MSCs, by which stem cells ameliorate inflammatory reactions. Modulation of adenosine signaling may help restore neurotransmitter balance, reduce neuroinflammation, and improve overall brain function in individuals with ASD. In our review article, we present a novel insight into purinergic signaling, including but not limited to the adenosinergic pathway and its role in neuroinflammation and neuro-immune cross-talk modulation. We anticipate that by achieving a greater understanding of the purinergic signaling contribution to ASD and related disorders, novel therapeutic strategies may be devised for patients with autism in the near future.