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The autism spectrum disorder (ASD) is an etiologically heterogeneous disorder. Dysfunctions of the intermediate metabolism have been described in some patients. We speculate these metabolic abnormalities are associated with brain insulin resistance (IR), i.e., the reduced glucose metabolism at the level of the nervous central system. The Homeostasis model assessment of insulin resistance (HOMA-IR) is very often used in population studies as estimate of peripheral IR and it has been recently recognized as proxy of brain IR. We investigated HOMA-IR in 60 ASD patients aged 4–18 years and 240 healthy controls, also aged 4–18 years, but unmatched for age, sex, body weight, or body mass index (BMI). At multivariable linear regression model, the HOMA-IR was 0.31 unit higher in ASD individuals than in controls, after having adjusted for sex, age, BMI z-score category, and lipids that are factors known to influence HOMA-IR. Findings of this preliminary study suggest it is worth investigating brain glucose metabolism in larger population of patients with ASD by using gold standard technique. The recognition of a reduced glucose metabolism in some areas of the brain as marker of autism might have tremendous impact on our understanding of the pathogenic mechanisms of the disease and in terms of public health.

Background: In the literature, several studies have proposed that children and adolescents with social anxiety had experienced previously victimization from peers and siblings. The aim of this review was to contribute to the updating of recent findings about the relationship between peer victimization and onset of social anxiety in children and adolescents. Methods: A selective review of literature published between 2011 and 2018 on Social Anxiety Disorder in children and adolescents that experienced peer victimization during childhood and adolescence. Results: Seventeen studies are included. All studies showed that peer victimization is positively correlated to the presence of social anxiety. Moreover, the perpetration of peer victimization may contribute to the maintenance and the exacerbation of social anxiety symptoms. Conclusions: In children and adolescents with Social Anxiety Disorder, it is necessary to evaluate firstly the presence of peer victimization experiences. Subsequently, therapeutics programs targeted to elaborate these experiences and to reduce the anticipatory anxiety and the avoidance that characterized these children and adolescents can be proposed.

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social interaction and repetitive behaviors (RBs). Therapies specifically targeting RBs have been underexplored despite advances in understanding their neurobiological basis. This study aims to evaluate whether high-definition transcranial direct current stimulation (HD-tDCS) can reduce dysfunctional RBs in autistic children and investigate whether improvements differ between lower-order and higher-order RBs based on the brain regions stimulated. Methods The study entails a multi-session, sham-controlled, site-controlled, double-blind, and between-subjects design. The study will include participants with an ASD diagnosis (aged 8–13 years; IQ ≥ 70), who will undergo the HD-tDCS intervention for 10 sessions. Participants will be randomly assigned to three conditions: (1) Pre-Motor Active Group (active HD-tDCS over pre-SMA cortex); (2) Frontal Active Group (active HD-tDCS over dlPFC); (3) Placebo Control Group. In the active HD-tDCS conditions, the current will be delivered through a 4 × 1 montage; small circular electrodes will be used with the cathode placed centrally with a current intensity of 0.5 mA for a total of 20 min (30 s ramp up/down) per session. Participants during the sham condition will undergo the same procedures as those in the both active conditions actual placement of electrodes, and turning on the HD-tDCS equipment (30 s). The assessment will be completed at baseline (T0), immediately after the end of the intervention (T1) and 3 months after the end of the intervention (T2). The primary outcome measure will be the Total Score of the Repetitive Behavior Scale-Revised. The secondary outcomes measures will comprise ASD symptoms, sensory processing pattern, emotional/behavioral problems, sleep functioning, parental stress, neuropsychological features and High-Density EEG connectivity. We hypothesize that active HD-tDCS will lead to significant reduction in the total score of the primary outcome compared to Sham Group, with site-specific effects on lower-order and higher-order RBs. Discussion HD-tDCS is an easy-to-deliver, time-efficient, neurobiologically-driven intervention that could be performed as add-on to reduce the time of conventional therapy for ASD. Given the inherent limitations of specific interventions for RBs, tDCS represents an important “third” treatment arm to address the burden of interventions for ASD. Trial registration details The trial has been registered at ClinicalTrials.gov (ID: NCT06645587). Registered 17 October 2024.

Findings regarding sex differences in autism spectrum disorder (ASD), as far as core symptoms and psychiatric comorbidities (PC) are concerned, are inconsistent, inconclusive, or conflicting among studies. The lower prevalence of ASD in females than in males and the age and intelligence quotient (IQ) heterogeneity among samples made it difficult to investigate these differences. This case–control study tries to deepen the impact of sex differences on core symptoms of autism and PC in 214 preschoolers with ASD (mean age, 45.26) without impairment in non-verbal IQ (nvIQ ≥70). A total of 107 ASD females (mean age, 44.51 ± 13.79 months) were matched one by one with 107 males (mean age, 46.01 ± 13.42 months) for chronological age (±6 months) and nvIQ (±6 points). We used the Autism Diagnostic Observation Schedule 2 (ADOS-2) and the Child Behavior Checklist (CBCL) 1.5–5 to explore autism severity and PC. The results highlight that ASD females did not significantly differ from ASD males regarding the severity of autism. Statistically significant lower levels of emotionally reactive ( p = 0.005, η 2 = 0.04), anxious-depressed ( p = 0.001, η 2 = 0.05), internalizing problems ( p = 0.04, η 2 = 0.02), and DSM-Oriented Scales anxiety problems ( p = 0.02, η 2 = 0.04) in ASD females than in ASD males were also detected. Our findings of no difference in the autism severity and lower internalizing problems in females than males with ASD extend the knowledge of autism in females during preschool years. Compared to other similar studies on this topic, we can state that these results are not supported by differences in nvIQ between sexes nor by the presence of cognitive impairment. It confirms the need for clinicians to consider sex differences when describing autism psychopathology.

Background: Anxiety Disorder (AD) is among the most common psychiatric comorbidity in children and adolescents with Autism Spectrum Disorder (ASD). Likewise, parental psychological distress (PPD) was linked to anxiety symptoms in children and adolescents with ASD. The aim of this study was to characterise, in a sample of children and adolescents with ASD, anxiety symptoms, the functional impairment associated and the presence of PPD. Methods: Participants were divided into three groups based on their diagnosis: children and adolescents with a diagnosis of ASD + AD, others with a diagnosis of AD but without a diagnosis of ASD, and others with a diagnosis of ASD but without a diagnosis of AD. Results: Group ASD + AD showed lower global functioning than Group ASD and Group AD. Generalised Anxiety Disorder, Separation Anxiety Disorder and Specific Phobias were more frequent in Group ASD + AD. Our findings also showed higher depressive symptoms in Group ASD + AD, both in the child and parent reports. Finally, parents of the Group ASD + AD revealed higher levels of PPD. Conclusions: Our findings suggest that early assessment of AD with functional impairment associated with the role of PPD could define individualised treatments and consequently mean a better prognosis in children and adolescents with ASD and AD.

Background/Objectives: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by social communication impairments and repetitive behaviors. Recent reports show that one in thirty-six 8-year-old children are autistic, signifying a considerable public health concern. According to previous studies, emotional dysregulation (ED) affects 50–60% of individuals with ASD and includes symptoms such as poor emotional control, heightened reactivity, and a low frustration tolerance. The main aims of the current study are to investigate the prevalence of ED among autistic preschoolers (below 6 years of age) and to assess the impacts of gender and intellectual disability on their emotional dysregulation profile. Methods: Data have been collected from three children’s research hospitals in Italy (IRCCS Stella Maris Foundation, Stella Maris Mediterraneo Foundation, and IRCCS Bambino Gesù). Parents of 825 autistic pre-schooled children (mean age: 39.68 months, SD: 10.51 months) completed a general questionnaire and the Child Behaviour Checklist (CBCL), a reliable caregiver-reported assessment tool which provides a dysregulation profile. Results: A total of 30% of the children displayed a severe-to-moderate ED (emotional dysregulation) profile, with these children exhibiting significantly higher emotional–behavioral problems compared to those without ED. Males with ED exhibited greater emotional reactivity than females with ED. However, no significant relationships were found between ED and age, autism severity (ADOS-2), or intellectual disability. Conclusions: The results underline the importance of early, tailored interventions to face emotional challenges in young children with ASD, potentially improving long-term outcomes for this population.

Background: To date, there have been numerous metataxonomic studies on gut microbiota (GM) profiling based on the analyses of data from public repositories. However, differences in study population and wet and dry pipelines have produced discordant results. Herein, we propose a biostatistical approach to remove these batch effects for the GM characterization in the case of autism spectrum disorders (ASDs). Methods: An original dataset of GM profiles from patients with ASD was ecologically characterized and compared with GM public digital profiles of age-matched neurotypical controls (NCs). Also, GM data from seven case–control studies on ASD were retrieved from the NCBI platform and exploited for analysis. Hence, on each dataset, conditional quantile regression (CQR) was performed to reduce the batch effects originating from both technical and geographical confounders affecting the GM-related data. This method was further applied to the whole dataset matrix, obtained by merging all datasets. The ASD GM markers were identified by the random forest (RF) model. Results: We observed a different GM profile in patients with ASD compared with NC subjects. Moreover, a significant reduction of technical- and geographical-dependent batch effects in all datasets was achieved. We identified Bacteroides_H, Faecalibacterium, Gemmiger_A_73129, Blautia_A_141781, Bifidobacterium_388775, and Phocaeicola_A_858004 as robust GM bacterial biomarkers of ASD. Finally, our validation approach provided evidence of the validity of the QCR method, showing high values of accuracy, specificity, sensitivity, and AUC-ROC. Conclusions: Herein, we proposed an updated biostatistical approach to reduce the technical and geographical batch effects that may negatively affect the description of bacterial composition in microbiota studies.

Background: Gestural production, a crucial aspect of nonverbal communication, plays a key role in the development of verbal and socio-communicative skills. Delays in gestural development often impede verbal acquisition and social interaction in children with Autism Spectrum Disorder (ASD). Although various interventions for ASD focus on improving socio-communicative abilities, they consistently highlight the importance of integrating gestures to support overall communication development. This study aimed to investigate the progression of gestural production in preschoolers with ASD one year post-diagnosis, taking into account whether they had received interventions for ASD. Method: This study followed 76 Italian preschoolers with ASD, aged 2 to 4 years, who underwent three different types of interventions or no intervention at all. Data on gestural production were collected using the MCDI, a standardized parent-proxy report. Results: The results indicate that all groups, regardless of intervention type, experienced increased gesture production, suggesting that interventions, combined with factors like time, symptom severity, and learning differences unique to ASD, positively influence nonverbal communication. This improvement may be due to various factors. On one hand, joint attention and socio-communicative interactions drive progress, while on the other, children with ASD may benefit from learning through non-socially mediated linguistic material. Conclusions: These findings highlight the need to understand individual learning preferences and strategies for developing nonverbal communication skills in children with ASD. Identifying effective strategies early on can enhance both diagnosis and intervention planning, ensuring they are tailored to the specific developmental needs of each child.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Investigations of gut microbiota (GM) play an important role in deciphering disease severity and symptoms. Overall, we stratified 70 ASD patients by neuropsychological assessment, based on Calibrated Severity Scores (CSSs) of the Autism Diagnostic Observation Schedule-Second edition (ADOS-2), Child Behavior Checklist (CBCL) and intelligent quotient/developmental quotient (IQ/DQ) parameters. Hence, metataxonomy and PICRUSt-based KEGG predictions of fecal GM were assessed for each clinical subset. Here, 60% of ASD patients showed mild to moderate autism, while the remaining 40% showed severe symptoms; 23% showed no clinical symptoms, 21% had a risk of behavior problems and 56% had clinical symptoms based on the CBCL, which assesses internalizing problems; further, 52% had no clinical symptoms, 21% showed risk, and 26% had clinical symptoms classified by CBCL externalizing problems. Considering the total CBCL index, 34% showed no clinical symptoms, 13% showed risk, and 52% had clinical symptoms. Here, 70% of ASD patients showed cognitive impairment/developmental delay (CI/DD). The GM of ASDs with severe autism was characterized by an increase in Veillonella, a decrease in Monoglobus pectinilyticus and a higher microbial dysbiosis index (MDI) when compared to mild-moderate ASDs. Patients at risk for behavior problems and showing clinical symptoms were characterized by a GM with an increase of Clostridium, Eggerthella, Blautia, Intestinibacter, Coprococcus, Ruminococcus, Onthenecus and Bariatricus, respectively. Peptidoglycan biosynthesis and biofilm formation KEGGs characterized patients with clinical symptoms, while potential microbiota-activated PPAR-γ-signaling was seen in CI/DD patients. This evidence derived from GM profiling may be used to further improve ASD understanding, leasing to a better comprehension of the neurological phenotype.

Background: Some studies have shown that anxiety is particularly frequent in the Clinical High Risk (CHR) for psychosis population. Notably, social anxiety disorder is identified as one of the most common anxiety disorders in CHR adolescents and young adults. Despite this, the frequency and the clinical significance of social anxiety in this population have been underestimated. Methods: A selective review of literature published between 2011 and 2017 on social anxiety disorder in CHR adolescents and young adults. Results: Five studies are included. In particular, three studies demonstrated that CHR adolescents and young adults have higher levels of anxiety compared to controls. Furthermore, anxiety, including social anxiety, is related to the severity of psychotic symptoms. The other studies included show inconsistent results regarding the possible relationship between social anxiety and social functioning. Conclusions: To date, the eidence concerning the comorbidity of social anxiety disorder and CHR in adolescents and young adults is not sufficient to provide clear guidelines for clinical practice. Future longitudinal studies on larger samples of the CHR adolescents and young adults are required to examine the relationship between social anxiety disorder and the presence of attenuated psychotic symptomatology.