Sickle cell disease (SCD) is a chronic illness accounting for 134,000 hospital admissions annually. Youth with SCD and youth with autism spectrum disorder (ASD) experience health disparities, yet the hospitalization outcomes of these youth have not been assessed. This study aimed to (i) determine the prevalence of ASD and selected neurodevelopmental disabilities (NDD) among hospitalized youth with SCD and (ii) compare hospitalization outcomes in youth with selected NDD and SCD to youth with SCD.

ICD-10 diagnosis codes were used to identify admitted youth (2-18 year olds) with SCD, ASD, and selected NDD (i.e., developmental delay) in the Pediatric Health Information System (October 2015 to April 2024). Demographic (age, race) and clinical variables (length of stay, intensive care unit [ICU] admission, 30-day readmissions, hydroxyurea use, genotype) were assessed.

Among 16,369 unique inpatients diagnosed with SCD (54.7% hemoglobin SS, median age = 11.9 years, and 86.4% non-Hispanic Black), 2.6% were diagnosed with a selected NDD; 1.7% were diagnosed with ASD. Hydroxyurea use during hospitalization did not differ between groups (3.3% vs. 3.5%; p = 0.19). Individuals with selected NDD had significantly higher annualized rates of hospitalization (0.88 vs. 0.65; p < .0001), ICU admission (0.12 vs. 0.05; p < .0001), and 30-day readmissions (20.2% vs. 17.4%; p = 0.0004) compared to youth without these neurodevelopmental diagnoses. The median length of stay in both groups was 3 days.

Youth with selected NDD and SCD are at an increased risk of frequent and complicated hospitalizations. Additional research should investigate how inpatient and outpatient care delivery can be tailored and optimized to reduce the frequency and severity of hospitalizations.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by impairments in social communication and restricted/repetitive behavioral patterns, has increased significantly over the past few decades. The etiology of ASD involves a highly complex interplay of genetic, neurobiological, and environmental factors, contributing to significant heterogeneity in its clinical phenotype. In the evolving landscape of ASD research, increasing evidence suggests that oxidative stress, resulting from both intrinsic and extrinsic factors, may be a crucial pathophysiological driver in ASD, influencing neurodevelopmental processes that underlie behavioral abnormalities. Elevated levels of oxidative stress biomarkers, including lipid peroxides, protein oxidation products, and DNA damage markers, alongside deficient antioxidant enzyme activity, have been consistently linked to ASD. This may be attributed to dysregulated activity of nuclear factor erythroid 2-related factor 2 (NRF2), a pivotal transcription factor that maintains cellular redox homeostasis by orchestrating the expression of genes involved in antioxidant defenses. Here, we summarize the converging evidence that redox imbalance in ASD may result from NRF2 dysregulation, leading to reduced expression of its target genes. We also highlight the most promising antioxidant compounds under investigation, which may restore NRF2 activity and ameliorate ASD behavioral symptoms.

PTPδ, encoded by PTPRD, is implicated in various neurological, psychiatric, and neurodevelopmental disorders, but the underlying mechanisms remain unclear. PTPδ trans-synaptically interacts with multiple postsynaptic adhesion molecules, which involves its extracellular alternatively spliced mini-exons, meA and meB. While PTPδ-meA functions have been studied in vivo, PTPδ-meB has not been studied. Here, we report that, unlike homozygous PTPδ-meA-mutant mice, homozygous PTPδ-meB-mutant (Ptprd-meB-/-) mice show markedly reduced early postnatal survival. Heterozygous Ptprd-meB+/- male mice show behavioral abnormalities and decreased excitatory synaptic density and transmission in dentate gyrus granule cells (DG-GCs). Proteomic analyses identify decreased postsynaptic density levels of IL1RAP, a known trans-synaptic partner of meB-containing PTPδ. Accordingly, IL1RAP-mutant mice show decreased excitatory synaptic transmission in DG-GCs. Ptprd-meB+/- DG interneurons with minimal IL1RAP expression show increased excitatory synaptic density and transmission. Therefore, PTPδ-meB is important for survival, synaptic, and behavioral phenotypes and regulates excitatory synapses in cell-type-specific and IL1RAP-dependent manners.

Autism Spectrum Disorder (ASD) is a range of neurodevelopmental conditions characterized by impaired social interaction, learning, and restricted or repetitive behaviors. The underlying causes of ASD are still debated, but researchers have found many physiological traits like gut problems and impaired immune system to help understand the etiology of ASD. Cerebrospinal fluid (CSF) plays a critical role in maintaining the homeostasis of the neuronal environment and has, therefore, been analyzed in multiple conditions impacting the central nervous system. The study of CSF is crucial to understanding neurological disorders as its composition changes with the disorders, and these changes may indicate various disorder-related physiological mechanisms. For this systematic review, we searched PubMed, Scopus, and Web of Science for studies published between 1977 and 2025 and selected 49 studies after manual screening. We took stock of the evidence supporting the hypothesis that ASD alters the properties and composition of CSF. We systematically report on the different attributes of CSF in the ASD population that could be potential biomarkers and assist in understanding the origins and progression of ASD. We found that in CSF, immune markers, proteins, extra-axial CSF, folate, oxytocin, and vasopressin showed changes in ASD compared to the neurotypicals. We observed gaps in the literature due to variations in age and sample size and noted biases related to sex (i.e., samples are predominantly including male participants) and age (i.e., a handful of studies were conducted on adults). Our review highlights the need for more research on CSF in ASD to improve our understanding of this disorder and identify CSF biomarkers.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication. Autistic individuals who are verbally fluent, often show difficulties in pragmatic ability, i.e. the capacity to use language and other expressive means, as gestures or the tone of the voice, to convey meaning in a given context. During the COVID-19 pandemic, the use of various technologies such as videoconferencing and internet for the delivery of healthcare services, i.e. telehealth, has proven to be effective, accessible and safe tools for remote healthcare. However, there are few tools to assess pragmatic skills in telehealth. This study investigates the effectiveness of the telehealth-adapted Assessment Battery for Communication (e-ABaCo), a clinical tool previously validated for in-person assessments, to evaluate pragmatic abilities in autistic individuals. We expect a substantial equivalence in performance for the administration of the adapted version of e-ABaCo compared to the face-to-face one.

We compared the performance of 30 autistic adolescents, of which 15 assessed via telehealth (ASD TH) and 15 assessed face-to-face (ASD FtF), with that of 15 adolescents with typical development (face-to-face assessment). The groups were matched for age, sex, and intellectual quotient. E-ABaCo was used to assess both comprehension and production of communicative ability realized through different expressive means, i.e. linguistic, extralinguistic and paralinguistic, as well as social appropriateness.

In line with the expectation, the pragmatic performance of autistic adolescents showed a substantial equivalence when comparing the assessments conducted via telehealth and face-to-face modality. Moreover, in line with the relevant literature, there was a significant difference between the ASD groups' performance (both FtF and TH) and the control group of the adolescents with typical development (CG FtF) in all pragmatic aspects assessed, i.e. the Pragmatic total score, comprehension and production abilities, and all the expressive means investigated.

These results confirm the potential usefulness of telehealth assessment procedures, and demonstrate the sensitivity and validity of e-ABaCo for conducting an effective assessment of pragmatic skills in on-line modality in autistic adolescents.

Over the past decade or so, mouse models of autism spectrum disorders (ASD) have been extensively studied in the search for key mechanisms underlying the disorder. Numerous intriguing mechanisms have been proposed, spanning various levels of the neural system, including molecular, synaptic, neuronal, circuit, and systems-level processes. However, no single mechanism has emerged as universally applicable, highlighting the heterogeneous nature of the genetic and neurobiological underpinnings of ASD. Among these, the NMDA receptor (NMDAR) dysfunction hypothesis has garnered significant attention. Many mouse models exhibit NMDAR dysfunction, with NMDAR hypofunction appearing more prevalent than hyperfunction. Nevertheless, not all mouse models display this dysfunction, suggesting that NMDAR abnormalities may not be ubiquitous across models, or that we have yet to fully explore the spectrum of NMDAR-related dysfunction in ASD. These findings underscore the need to consider multiple factors when studying ASD mouse models, including different mutations within the same gene, gene deletion dosage, genetic background, sex, age, brain regions, cell types, and neural circuits.

Divergent age-related functional brain connectivity in autism spectrum disorder (ASD) has been observed using resting-state fMRI, although the specific findings are inconsistent across studies. Common statistical regression approaches that fit identical models across functional brain networks may contribute to these inconsistencies. Relationships among functional networks have been reported to follow unique nonlinear developmental trajectories, suggesting the need for flexible modeling. Here we apply generalized additive models (GAMs) to flexibly adapt to distinct network trajectories and simultaneously describe divergent age-related changes from childhood into mid-adulthood in ASD.

1107 males, aged 5-40, from the ABIDE I & II cross-sectional datasets were analyzed. Functional connectivity was extracted using a network-based template. Connectivity values were harmonized using COMBAT-GAM. Connectivity-age relationships were assessed with thin-plate spline GAMs. Post-hoc analyses defined the age-ranges of divergent aging in ASD.

Typically developing (TD) and ASD groups shared 15 brain connections that significantly changed with age (FDR-corrected p < 0.05). Network connectivity exhibited diverse nonlinear age-related trajectories across the functional connectome. Comparing ASD and TD groups, default mode to central executive between-network connectivity followed similar nonlinear paths with no group differences. Contrarily, the ASD group had chronic hypoconnectivity throughout default mode-ventral attentional (salience) and default mode-somatomotor aging trajectories. Within-network somatomotor connectivity was similar between groups in childhood but diverged in adolescence with the ASD group showing decreased within-network connectivity. Network connectivity between the somatomotor network and various other functional networks had fully disrupted age-related pathways in ASD compared to TD, displaying significantly different model curvatures and fits.

The present analysis includes only male participants and has a restricted age range, limiting analysis of early development and later life aging, years 40 and beyond. Additionally, our analysis is limited to large-scale network cortical functional parcellation. To parse more specificity of brain region connectivity, a fine-grained functional parcellation including subcortical areas may be warranted.

Flexible non-linear modeling minimizes statistical assumptions and allows diagnosis-related brain connections to follow independent data-driven age-related pathways. Using GAMs, we describe complex age-related pathways throughout the human connectome and observe distinct periods of divergence in autism.

With the development and improvement of technology, live streaming systems have emerged in people's daily lives, providing new channels for agricultural product sales. This study aims to understand how to scientifically design live streaming systems for agricultural product sales based on user perceptions and preferences. We conducted an online survey, and Study 1 obtained 569 valid samples. We established a structural equation model and applied fuzzy-set qualitative comparative analysis to identify necessary conditions and configurations. In Study 2, two survey stages obtained 61 and 228 valid samples, respectively, and exploratory factor analysis was used for dimensionality reduction. The results showed that information quality and perceived interactivity can reduce social anxiety in female and male users, respectively. Information quality and perceived playfulness positively affect purchase intention. Furthermore, we identified four positive factors, including natural quality, support for domestic agriculture, transportation services, and information attractiveness, and three negative factors, including fulfillment risk, decision pressure, and inefficient consumption experience that may influence users' purchase intention. The findings provide validated design insights for live streaming systems, playing a positive role in enhancing design effectiveness and promoting agricultural product sales.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. Hyperandrogenism has been proposed as its main pathophysiological feature. PCOS is associated with co-occurring conditions, including psychiatric disorders such as anxiety, depression, and neurodevelopmental conditions such as autism. Exposure to hyperandrogenism during prenatal life and adolescence may explain this association. PCOS women exhibit hyperandrogenism during pregnancy, and up to 70% of their daughters will present a similar phenotype from puberty onwards. The 'dual hit hypothesis' proposes that stressors during prenatal life and adolescence can synergistically lead to co-occurring conditions in adulthood. PCOS has been recently proposed as an independent likelihood factor for the development of neuropsychiatric conditions. However, the specific mechanisms require further research to develop effective interventions. This review discusses how hyperandrogenism can affect neurodevelopment during two key periods of brain development, which may explain the long-term impact of PCOS on mental health.

children with ASD have a higher percentage of obesity compared to neurotypical children of the same age. Diet problems can lead to excesses or deficiencies in the consumption of macro and micronutrients.

to rigorously and serially evaluate the anthropometric and dietary data of ASD patients of preschool and school age over a period of 6 months.

a longitudinal study that included 34 children diagnosed with ASD of both sexes, from 4 to 11 years of age, recruited at convenience in the Mental Health Service of the National Institute of Pediatrics in Mexico City. The variables considered were: age, body mass index with Z-score and intake of macro and micronutrients.

at the end of the follow-up, 25 of 34 patients concluded the study and their nutritional status showed changes that did not have statistical significance, where 4 % were underweight, 56 % were normal weight, 12 % were overweight and 28 % were obese. Macronutrients, such as energy and fiber, and micronutrients, such as zinc, vitamin D, omega-3 and omega-6, and tryptophan, showed imbalances in consumption by patients without statistical significant changes in time.

there is an imbalance in the consumption of macro and micronutrients in children with ASD and the prevalence of obesity is higher compared to other studies.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that affect children's social interaction and communication skills and exert a serious effect on children's perception, language, emotion, and especially social interaction development.

To determine the clinical and psychological characteristics of children with ASD according to the C-PEP-3.

This retrospective study included 225 children with autism aged 2-7 years who were treated in our hospital from 2021 to 2024. The C-PEP-3 scale was used for assessment, and the evaluation results were analyzed.

The comparison of children with ASD in the age groups of < 3.5 years and > 3.5 years revealed significant differences in the scores of imitation, fine motor, gross motor, hand-eye coordination, cognitive performance, and verbal cognition development areas (P: Pass) (P < 0.01). However, no significant differences in the scores of perception, emotion, interpersonal relationships, play, sensation, and language (S: Severe) were observed on pathological scales (P > 0.05). The difference in age in the gross motor developmental delay of the scale was the smallest, whereas that of the verbal cognition was the largest, followed by the imitation functional area. An inverse correlation was found between the scores of imitation, perception, hand-eye coordination, and cognitive performance (P) developmental function areas in children with ASD and those of emotion, interpersonal relationships, game and item preferences, sensory patterns, and emotion (S) in the pathological scale (P < 0.05). Fine and gross motor skills were negatively correlated with interpersonal relationships, game and item preferences, and emotions in the pathological scale (P < 0.05). Age was significantly positively correlated with the scores of imitation, perception, fine motor, gross motor, hand-eye coordination, cognitive performance, and verbal cognition developmental function areas (P) (P < 0.05). Further, age was not associated with emotions, interpersonal relationships, game and item preferences, sensory patterns, and emotions (P > 0.05). No gender difference was observed between the scores of each developmental area (P) of the scale and the scores of each functional area (S) of the pathological scale.

The C-PEP-3 scale reflects the differences in clinical characteristics of children with autism, and the pathological scale is associated with the severity of developmental function areas. The C-PEP-3 scale can be utilized to assess the effect of age changes on children with autism. Attention in rehabilitation should be focused on addressing the pathological behaviors of children with autism.

Face perception is fundamental to social cognition and often disrupted in autism. However, the neurological basis for this disrupted face perception and the mechanisms underlying altered electrophysiological signaling in autism, such as increased latency of the N170-an electrophysiological marker of face processing, remain unknown. Here, we leverage multimodal neuroimaging in autistic adolescents to establish a link between MRI-measured axonal microstructure within the face processing network and EEG-measured N170 latency. We demonstrate that a novel metric of axonal signal transit time derived from axonal diameter, myelination, and length-estimated axonal latency (EAL)-predicts N170 latency during face processing. Moreover, we demonstrate that individuals with and without autism rely upon different pathways, providing a structural account for autism-related face processing differences. By establishing this relationship between EEG-based electrical function and MRI-based axonal microstructure, we provide a non-invasive, spatially-detailed estimate of neuronal processing speed that can inform understanding of brain function, development, and disorder.

Neuroinflammation triggered by microglia activation is hallmark of autism spectrum disorder (ASD), and this process includes crucial metabolic reprogramming from oxidative phosphorylation to glycolysis, which may cause neuron loss and functional impairment. The inhibitory immune checkpoint programmed cell death protein 1 (PD-1) on immune cells is an important target for tumor immunotherapy. However, the immunomodulatory effects of PD-1 in ASD remains to be elusive. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exhibit immunomodulatory capabilities in a range of neurological diseases. Our findings indicated the expression of PD-L1 on MSC-EVs, potentially facilitating signaling to PD-1-expressing microglia. Here, we showed how MSC-EVs activated of PD-L1/PD-1 axis and ameliorated glycolysis, neuroinflammation and autism-like behaviors. After first detecting elevated glycolysis and neuroinflammation in prefrontal cortex (PFC) tissue from the maternal immune activation (MIA) mice, we also demonstrated that PD-1 expression level was upregulated in microglia. Following given MSC-EVs carried PD-L1 into adult MIA offspring mice via intranasal administration, which bound with PD-1 on microglia and then the autism-like behaviors were alleviated as well. Further experiments verified that MSC-EVs could decreased the level of glycolysis and neuroinflammation by PD-1/ERK/HIF-1α pathway in the primary microglia in PFC of MIA offspring mice. Pharmacological blockade and genetic inhibition of PD-1 could weaken the effect of MSC-EVs and aggravate microglial dysfunction, glycolysis and autism-like behaviors in MIA offspring mice. Futhermore, PD-L1 deficient weakened the effect of MSC-EVs on neuroinflammation, glycolysis and autism-like behaviors in MIA offspring mice. Our research indicated the significant immunomodulatory capabilities of MSC-EVs, which play an important role in reprogramming microglial glucose metabolism and suppressing neuroinflammation in ASD. By activating the PD-L1/PD-1 axis and inhibiting the downstream ERK/HIF-1α pathway, MSC-EVs were found to alleviate autism-like behaviors, which revealing a novel pathological mechanism and offering promising therapeutic insights into ASD.

Introduction: Autism and ADHD shape behaviours related to food, exercise, and body image, potentially influencing obesity treatment outcomes, as seen in eating disorder research. Resultantly, autistic and ADHD patients with obesity may have distinct experiences and differences compared to non-autistic and non-ADHD patients. This review maps existing literature on autism and ADHD in adults with obesity. Methods: Following PRISMA guidelines, six databases (Embase, MEDLINE, PsycINFO, Web of Science, CENTRAL, and Scopus) were searched for studies on autism and/or ADHD (diagnosed, probable, or traits) in adults with obesity. Screening and data extraction were conducted twice independently for each record. Results: Thirty-one studies were included, with 1,027,773 participants. Two case reports described successful use of weight loss drugs in autistic people with obesity. Eight prevalence studies suggested ADHD is overrepresented in obesity, regardless of binge eating status. Nineteen studies examined clinical profiles: ADHD patients had lower socioeconomic status, poorer health-related quality of life, increased impulsivity, cognitive inflexibility, and neuroticism, alongside lower agreeableness, conscientiousness, self-directedness, and cooperativeness. ADHD patients also exhibited higher psychopathology, problematic alcohol use, and disordered eating. Eight studies assessed treatment responses, noting poorer outcomes from behavioural programs and obesity pharmacotherapy, but similar post-surgical weight outcomes, despite increased complications. Two studies considered ADHD-specific treatment adaptions, one reporting a successful trial of ADHD medication for weight loss and the other reporting on switching to transdermal ADHD medications after bariatric surgery. Conclusions: This review underscores the need for more research on autism and obesity. For ADHD, findings suggest frequent co-occurrence with obesity, but lived experiences and tailored interventions remain underexplored.

Previous eye-tracking research on autistic individuals has mostly examined the gaze behavior of one individual in response to social stimuli presented on a computer screen, suggesting that there is atypical gaze behavior. However, it is unknown how these findings translate to the interactive dynamics of gaze behavior during "face-to-face" encounters between two individuals. Only by analyzing the gaze behaviour of both interaction partners is it possible to determine the frequency of actual eye-contact and who initiates or breaks such periods of mutual eye gaze. The knowledge gained from this analysis could contribute to theorizing about the psychological mechanisms (e.g., gaze avoidance vs. gaze indifference) underlying autism.

The present study applied a novel dual eye-tracking setup that allows the assessment and analysis of the interactive dynamics of gaze behavior regarding (i) mutual eye gaze (i.e., eye contact), (ii) initiations, and (iii) break-ups of eye contact. Participants (37 autistic individuals, 37 age- and IQ-matched neurotypical individuals) performed a semi-standardized social interaction (i.e., Fast Friends Procedure) with a confederate (trained to interact in a standardized manner).

Eye contact was reduced in interactions involving autistic individuals. Additional analyses revealed that this reduction was primarily due to the more frequent breaking of eye contact by these individuals. We also found considerable heterogeneity among autistic individuals, with atypical gaze behavior present in only about half of the sample.

Further research is required to determine whether the interactive dynamics of gaze behavior observed in this dual eye-tracking setup can be generalized to real-world situations. Future studies could also include arousal-related physiological measures.

By tracking the gaze behavior of two interacting individuals, this study reveals specific atypicalities in the interactive dynamics of gaze behavior in a subset of autistic individuals, potentially informing diagnostic and therapeutic decisions. More broadly, our study highlights the added value of dual eye-tracking in elucidating the interactive nature of social encounters in both neurodiverse and neurotypical individuals.

The study was registered as a clinical trial before starting data collection ( https://drks.de/search/en/trial/DRKS00018957 ; Registration Date: 12/17/2019).

Sex differences in brain development are thought to lead to sex variation in social behavior. Sex differences are fundamentally driven by both gonadal hormones and sex chromosomes, yet little is known about the independent effects of each on social behavior. Further, mouse models of the genetic liability for the neurodevelopmental disorder MYT1L Syndrome have shown sex-specific deficits in social motivation. In this study, we aimed to determine if gonadal hormones or sex chromosomes primarily mediate the sex differences seen in mouse social behavior, both at baseline and in the context of Myt1l haploinsufficiency.

Four-core genotypes (FCG) mice, which uncouple gonadal and chromosomal sex, were crossed with MYT1L heterozygous mice to create eight different groups with unique combinations of sex factors and MYT1L genotype. A total of 131 mice from all eight groups were assayed for activity and social behavior via the open field and social operant paradigms. Measures of social seeking and orienting were analyzed for main effects of chromosome, gonads, and their interactions with Myt1l mutation.

The FCGxMYT1L cross revealed independent effects of both gonadal and chromosomal sex on activity and social behavior. Specifically, the presence of ovarian hormones led to greater overall activity, social seeking, and social orienting regardless of MYT1L genotype. In contrast, sex chromosomes affected social behavior mainly in the MYT1L heterozygous group, with XX MYT1L mutant mice demonstrating elevated levels of social orienting and seeking compared to XY MYT1L mutant mice.

Gonadal and chromosomal sex have independent mechanisms of driving greater social motivation in females. Additionally, genes on the sex chromosomes may interact with neurodevelopmental risk genes to influence sex variation in atypical social behavior.

Down syndrome (DS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders characterized by impairments in language. Most studies do not consider the possible role sex differences may play in language profiles. Thus, the current study aimed to evaluate whether parent-reported structural and pragmatic language vary as a function of sex in youth with DS (n = 37), ASD (n = 106), and typical development (TD; n = 61). Findings suggest a female advantage in both structural and pragmatic language in DS; in contrast, no sex differences were found for either ASD or TD. Results suggest that males with DS may require more extensive interventions for language. Future research should investigate how age, IQ, and mode of measurement may impact the nature of these observations.

The objective of this review was to analyze quantitative data on autism spectrum disorder (ASD) and to increase the accuracy of estimates of the prevalence of ASD.

This review, which was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, included studies conducted from January 2008 to June 2024 on children aged 3 to 18 years that used standardized measurement tools and reported cut-off scores for ASD. The prevalence of ASD was the primary outcome analyzed in this review. The PubMed, Clinical Key, Scopus, Embase, CINAHL, and Web of Science databases were reviewed for relevant studies. The review protocol was registered with PROSPERO and followed the Cochrane collaboration guidelines.

A total of 66 studies reported on the prevalence of ASD, screening 21,313,061 children worldwide. Among these, 25 studies were conducted in Europe, 22 in Asia, and 13 in America. Additionally, 3 studies each were reported from Africa and Australia. According to a meta-analysis, 0.77% of children globally are diagnosed with ASD, with boys comprising 1.14% of this group. Notably, Australia showed the highest prevalence rate, with an effect size of 2.18, highlighting it as a critical area for public health focus.

ASD represents a significant global health burden. Early detection, increased awareness among parents, and prompt intervention are crucial for mitigating developmental problems in children later in life. It is essential for health policymakers to acknowledge the prevalence and growing trends of ASD in order to implement effective interventions.

This review maps existing literature on the prevalence of autism and ADHD in adult patients with Bulimia Nervosa (BN) and Binge Eating Disorder (BED); patient and stakeholder perspectives on this comorbidity; clinical differences in this population; and potential treatment adaptations or adjunct therapies. This is with the aim to inform future research priorities to improve clinical practice.

As pre-registered, and following PRISMA guidelines, six databases (Embase, MEDLINE via Ovid, PsycINFO, Web of Science, CENTRAL, and Scopus) were searched for studies regarding autism and/or ADHD (diagnosed, probable, or traits) in adult patients with BN or BED. Screening and data extraction were conducted twice independently for each record.

Twenty-nine studies were included, with 25,416 participants, mostly women (69.3%). Thirteen prevalence studies suggested autism and ADHD are more common in BN or BED than non-ED populations. One study explored the expert perspectives on autism and ADHD in BED, while 15 studies considered treatment options, mainly medications.

This review highlights a need for more research on the experiences, clinical differences, and non-medical treatment options for Autistic/ADHD patients with BN or BED. Findings suggest these conditions commonly co-occur but remain under-explored in terms of patient-centred interventions and clinical outcomes.

Autistic individuals may show several psychiatric co-occurrences, including Feeding and Eating Disorders (FEDs). Avoidant and Restrictive Food Intake Disorder (ARFID) consists of avoidance or restriction in food intake, leading to significant weight loss, nutritional deficiencies, and marked interference with psychosocial functioning. Both Autism Spectrum Disorder (ASD) and ARFID are characterized by the two main features of cognitive rigidity and sensory sensitivity, which may complicate differential diagnosis. There is a notable lack of information on the manifestation of ASD-ARFID co-occurrence, as well as tailored assessment tools and practice, and therapeutic approaches.

This report provides a detailed description of L., a young girl with a late diagnosis of ASD who also developed unspecific depressive mood disorder and ARFID in co-occurrence. After the diagnosis of ASD, L. underwent multiple evaluations to address emerging psychiatric co-occurrences and symptom exacerbation, and in order to develop the most effective integrated treatment.

The case of L. expands the knowledge on the phenotype of Autistic females and exemplifies how delayed diagnosis may exacerbate functioning differences and increase the camouflage phenomenon. Additionally, it underscores the importance of improving tailored evaluation, combined treatment plans, with both cognitive-behavioral therapy and drugs, and monitoring the evolving patterns of Autistic manifestations and associated psychiatric co-occurrences.

Level 1 autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by challenges in social and communication skills. Despite these difficulties, individuals with level 1 ASD often exhibit average intelligence and typical language development. Improving socialisation skills in this population requires tailored approaches that address their specific needs and include targeted strategies. This study aims to evaluate the effectiveness of a structured social skills training programme for adolescents and young adults with level 1 ASD.

Participants diagnosed with level 1 ASD, regardless of gender, were consecutively recruited from an outpatient clinic. The intervention involved activities from the Social Skills, Autonomy, and Awareness Module, specifically designed for adolescents and young adults. Sessions were conducted fortnightly, lasting 1.5 to 3 h each, over 17 months. Adaptive behaviour was assessed using the Vineland Adaptive Behaviour Scales (VABS) at baseline and after completing the programme. Data were analysed with SPSS version 22.0 (SPSS Inc., Chicago, IL, USA). Statistical methods included automatic clustering to identify optimal clusters and Pearson's Chi-square and Fisher's exact tests to evaluate variable distributions among the clusters.

A total of 31 participants (77.4% female) with a mean age of 20.1 years (SD = 7.0) were included in the study. Two distinct clusters emerged. Cluster 1 (n = 8) had significantly higher mean ages and baseline Vineland II socialisation scores than Cluster 2 (n = 23). Both clusters demonstrated significant improvements in social skills following the intervention.

This study highlights distinct profiles within individuals with level 1 ASD, showing a clear link between age and social skill development. The intervention improved social skills for most participants, regardless of the age at which treatment began. For some individuals, alternative or augmented treatment strategies may be necessary to achieve optimal results.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD. The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest symptoms similar to those in males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leaves them underrepresented in genome-wide studies. Here, we conducted an X-chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Collection (SSC), and Simons Powering Autism Research (SPARK), alongside 8,981 population controls (43% males). We analyzed 418,652 X chromosome variants, identifying 59 associated with ASD (p values 7.9 × 10-6 to 1.51 × 10-5), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on Xp22.2 (lead SNP rs12687599, p = 3.57 × 10-7) harboring ASB9/ASB11 and another encompassing DDX53 and the PTCHD1-AS long non-coding RNA (lead SNP rs5926125, p = 9.47 × 10-6). When mapping genes within 10 kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD (GRPR, AP1S2, DDX53, HDAC8, PCDH19, PTCHD1, PCDH11X, PTCHD1-AS, DMD, SYAP1, CNKSR2, GLRA2, OFD1, CDKL5, GPRASP2, NXF5, and SH3KBP1). FGF13 emerged as an X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation.

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

Previous research highlights impairments in the recognition of facial expression of emotion in individuals diagnosed with Autism Spectrum Disorder (ASD). Relatives of people with ASD may exhibit similar, albeit subtler, impairments, referred to as the Broad Autism Phenotype (BAP). Recently, the Differential outcomes procedure (DOP) has been shown to enhance this ability in young adults using dynamic stimuli, with fewer intensity levels required to identify fear and surprise. The present study aimed to extend these findings to adults diagnosed with ASD (ASD group), and relatives of people diagnosed with ASD (BAP group). A Bayesian Generalized Linear Model was employed for statistical inference. The results indicated that the ASD DOP group performed worse than the BAP DOP group in fear trials. The social dimension of autism negatively impacted performance in some conditions, while positive relationships were found between the repetitive behavior dimension and performance for the ASD group. The opposite pattern was observed in the BAP group. These results suggest the importance of considering different dimensions of autism when conducting research on its relationship with other variables. Finally, participants in both ASD and BAP groups required less intensity to identify certain emotions when the DOP was applied, highlighting its potential utility for improving dynamic facial emotion recognition.

The aim of the current study was to examine the psychometric properties of the Emotion Regulation and Social Skills Questionnaire (ERSSQ) among young Farsi-speaking individuals with Autism Spectrum Disorder (ASD) in Iran.

This cross-sectional study analyzed data from 108 children and teenagers (aged 7 to 14 years; mean age = 10.55 years, 91% male) with ASD, along with an equal number of neurotypical children, their families, and teachers. The assessment of the ERSSQ's psychometric properties included evaluations of reliability, content validity, and face validity. Cronbach's alpha coefficient was used to estimate the reliability of the ERSSQ-P and ERSSQ-T which were completed respectively by parents and teachers of children with autism spectrum disorders.

The results indicated that the Persian versions of the ERSSQ-P and ERSSQ-T questionnaires exhibited adequate face and content validity (CVI = 0.92 and 0.88, respectively). Additionally, both ERSSQ-P and ERSSQ-T demonstrated acceptable internal consistency, with Cronbach's alpha values of 0.95 and 0.70, respectively.

This study confirms the effectiveness and validity of the ERSSQ-P and ERSSQ-T, which can be utilized by specialists in the field of autism for clinical and research applications. These instruments offer a straightforward and cost-effective means of assessing emotion regulation and social skills among Farsi-speaking children and adolescents with ASD.

Sex differences in mental rotation are a well-documented phenomenon in cognitive research, with implications for the differing prevalence of neuropsychiatric disorders such as autism spectrum disorder (ASD), Alzheimer's disease (AD) and major depressive disorder (MDD) between the sexes. Despite extensive documentation, the biological mechanism underpinning these differences remain elusive. This study aimed to elucidate neural, genetic, and molecular bases of these disparities in mental rotation by integrating data from multimodal magnetic resonance imaging (MRI), transcriptomic and receptor/transporter. We first calculated the dynamic regional homogeneity (dReHo), gray matter volume (GMV) and fractional anisotropy (FA) in voxel-wise manner and parceled them into 246 brain regions based on Brainnetome Atlas. Subsequent analyses involved Pearson Correlations to examine the association between mental rotation performance and dReHo/GMV/FA and two-sample t-tests to delineate gender differences in these indices. Based on the above results, further mediation analysis was conducted to explore the relationship between sex, brain biomarkers and mental rotation. In addition, transcriptome-neuroimaging association analysis and correlation analysis between brain biomarkers and neurotransmitter receptor/transporter distribution were also performed to uncover genetic and molecular mechanisms contributing to the observed sex differences in mental rotation. We found correlations between mental rotation performance and dReHo, GMV and FA of the inferior parietal lobule (IPL) and superior temporal gyrus (STG) and sex effects on these brain biomarkers. Notably, the dReHo of the left IPL mediated the relationship between sex and mental rotation. Further correlation analysis revealed that the proton-coupled oligopeptide transporter PEPT2 (SLC15A2) and interleukin 17 receptor D (IL17RD) were associated with sex-related t-statistic maps and mental rotation-related r-statistic maps of dReHo. Moreover, γ-aminobutyric acid subtype A (GABAA) receptor availability was correlated with the r-statistic of dReHo, while norepinephrine transporter (NET) availability was correlated with its t-statistic. Serial mediation models revealed the indirect effect of these genes on the r-statistic maps through the transporter/receptor and t-statistic maps. Our findings provide novel insights into the biological mechanism underlying sex differences in mental rotation, identifying potential biomarkers for cognitive impairment and explaining variations in prevalence of certain mental disorders between the sexes. These results highlight the necessity of considering sex in research on mental health disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with altered brain activity. However, little is known about the integrated temporospatial variation of dynamic spontaneous brain activity in ASD. In the present study, resting-state functional magnetic resonance imaging data were analyzed for 105 ASD and 102 demographically-matched typically developmental controls (TC) children obtained from the Autism Brain Imaging Data Exchange database. Using the sliding-window approach, temporal, spatial, and temporospatial variability of dynamic amplitude of low-frequency fluctuation (tvALFF, svALFF, and tsvALFF) were calculated for each participant. Group-comparisons were further performed at global, network, and brain region levels to quantify differences between ASD and TC groups. The relationship between temporospatial dynamic amplitude of low-frequency fluctuation variation alterations and clinical symptoms of ASD was finally explored by a support vector regression model. Relative to TC, we found enhanced tvALFF in visual network (Vis), somatomotor network (SMT), and salience/ventral attention network (SVA) of ASD, and weakened tvALFF in dorsal attention network (DAN) of ASD. Besides, ASD showed decreased svALFF in Vis, SVA, and limbic network (Limbic), and increased svALFF in DAN and default mode network (DMN). Elevated tsvALFF was found in the Vis, SMT, and DMN of ASD. More importantly, the altered tsvALFF from the DMN can predict the symptom severity of ASD. These findings demonstrate altered temporospatial dynamics of the spontaneous brain activity in ASD and provide novel insights into the neural mechanism underlying ASD.

Autism spectrum disorder (ASD) has proven to be highly enigmatic due to the diversity of its underlying genetic causes and the huge variability in symptom presentation. Uncovering common phenotypes across people with ASD and pre-clinical models allows us to better understand the influence on brain function of the many different genetic and cellular processes thought to contribute to ASD aetiology. One such feature of ASD is the convergent evidence implicating abnormal functioning of the medial prefrontal cortex (mPFC) across studies. The mPFC is a key part of the 'social brain' and may contribute to many of the changes in social behaviour observed in people with ASD. Here we review recent evidence for mPFC involvement in both ASD and social behaviours. We also highlight how pre-clinical mouse models can be used to uncover important cellular and circuit-level mechanisms that may underly atypical social behaviours in ASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental diseases. Epidemiological data report that males have been diagnosed with autism more frequently than females. However, recent studies hypothesize that females' low incidence might be underestimated due to standard clinical measures of ASD behavioural symptoms, mostly derived from males. Indeed, up to now, ASD mouse models focused mainly on males, considering the prevalence of the diagnosis in that sex. Regarding ASD aetiopathogenesis, it has been recently reported that oxidative stress might be implicated in its onset and development, suggesting an association with ASD typical repetitive behaviours that still need to be disentangled. Here, we investigated possible behavioural and molecular sex-related differences by using the BTBR mouse model of idiopathic ASD. To this aim, animals were exposed to behavioural tests related to different ASD core symptoms and comorbidities, i.e. stereotyped repertoire, social dysfunctions, hyperlocomotion and risk-taking behaviours. Moreover, we analyzed hippocampal levels of pro-oxidant and anti-oxidant enzymes, together with biomarkers of oxidative stress and lipid peroxidation. Our results showed that BTBR females did not display the same patterns for repetitive behaviours as the male counterpart. From a biomolecular point of view, we found an increase in oxidative stress and pro-oxidant enzymes, accompanied by deficient enzymatic anti-oxidant response, only in BTBR males compared to C57BL/6 male mice, while no differences were retrieved in females. Overall, our study suggests that in females there is an urgent need to depict the distinct ASD symptomatology, accompanied by the identification of sex-specific pharmacological targets.

This study aimed to investigate the relationships between hoarding behaviors, autism characteristics, and demographic factors in adults diagnosed with high-functioning ASD (Autism Spectrum Disorder). A total of 112 adults, aged 18-35, with high-functioning ASD completed self-reported assessments on hoarding (Savings Inventory-Revised; SI-R) and autism traits (Autism-Spectrum Quotient; AQ). Additionally, demographic data was gathered. Correlation and regression analyses were performed. The findings revealed positive correlations between hoarding and overall autism traits. Autism quotient scores accounted for 24% of the variance in hoarding inventory scores. Higher AQ scores were associated with increased SI-R scores. Specific AQ subscales were linked to particular SI-R subscales. Gender, age, education level, and employment status were connected to assessment scores. A multiple regression analysis revealed that demographic variables accounted for 19% of the variance in hoarding severity. Gender was found to moderate the impact of age on hoarding behaviors. Significant associations were identified between hoarding tendencies and autism traits in adults with ASD. Demographic variables also played a role in symptom presentation. These findings shed light on the relationship between autism characteristics and hoarding behaviors, as well as how external factors influence them. Further research is necessary to enhance understanding and guide interventions for hoarding in ASD populations.

Reflecting sex and gender characteristics in biomedical research is critical to improving health outcomes and reducing adverse effects from medical treatments. This study investigates the impact of sex/gender-specific funding policies and journal editorial standards on the integration of sex/gender analysis in biomedical research publications. Using data from the United States, Canada, the United Kingdom, and other countries between 2000 and 2021, we assessed how these policies influenced research output in the fields of medicine and life sciences. Our findings show that countries with progressive funding policies and journals promoting sex/gender-based reporting have significantly improved research quality and publication rates. This highlights the importance of coordinated policy efforts and editorial practices in advancing integrated sex/gender research. We recommend continued global efforts from policymakers, funding bodies, and journals to embed sex/gender perspectives in scientific inquiry, ensuring more effective and equitable biomedical advancements.

Sex differences in brain development are thought to lead to sex variation in social behavior. Sex differences are fundamentally driven by both gonadal (i.e., hormonal) and chromosomal sex, yet little is known about the independent effects of each on social behavior. Further, mouse models of the genetic liability for the neurodevelopmental disorder MYT1L Syndrome have shown sex specific deficits in social motivation. In this study, we aimed to determine if hormonal or chromosomal sex primarily mediate the sex differences seen in mouse social behavior, both at baseline and in the context of Myt1l haploinsufficiency.

Four-core genotype (FCG) mice, which uncouple gonadal and chromosomal sex, were crossed with MYT1L heterozygous mice to create eight different groups with unique combinations of sex factors and MYT1L genotype. A total of 131 mice from all eight groups were assayed for activity and social behavior via the open field and social operant paradigms. Measures of social seeking and orienting were analyzed for main effects of chromosome, gonads, and their interactions with Myt1l mutation.

The FCGxMYT1L cross revealed independent effects of both gonadal and chromosomal sex on activity and social behavior. Specifically, the presence of ovaries, and by extension the presence of ovarian hormones, increased overall activity, social seeking, and social orienting regardless of genotype. In contrast, sex chromosomes affected social behavior mainly in the MYT1L heterozygous group, with XX sex karyotype when combined with MYT1L genotype contributing to increased social orienting and seeking.

Gonadal and chromosomal sex have independent mechanisms of driving increased social motivation in females. Additionally, sex chromosomes may interact with neurodevelopmental mutations to influence sex variation in atypical social behavior.

Autism spectrum disorder (ASD) is a heterogeneous, early-onset neurodevelopmental condition characterized by persistent impairments in social interaction and communication. This study aims to delineate ASD subtypes based on individual gray matter brain networks and provide new insights from a graph theory perspective. In this study, we extracted and normalized single-subject gray matter networks and calculated each network's topological properties. The heterogeneity through discriminative analysis (HYDRA) method was utilized to subtype all patients based on network properties. Next, we explored the differences among ASD subtypes in terms of network properties and clinical measures. Our investigation identified three distinct ASD subtypes. In the case-control study, these subtypes exhibited significant differences, particularly in the precentral gyrus, lingual gyrus, and middle frontal gyrus. In the case analysis, significant differences in global and nodal properties were observed between any two subtypes. Clinically, subtype 1 showed lower VIQ and PIQ compared to subtype 3, but exhibited higher scores in ADOS-Communication and ADOS-Total compared to subtype 2. The results highlight the distinct brain network properties and behaviors among different subtypes of male patients with ASD, providing valuable insights into the neural mechanisms underlying ASD heterogeneity.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a diverse profile of cognitive functions. Heterogeneity is observed among both baseline and comorbid features concerning the diversity of neuropathology in autism. Symptoms vary depending on the developmental stage, level of severity, or comorbidity with other medical or psychiatric diagnoses such as intellectual disability, epilepsy, and anxiety disorders.

The neurodiversity movement does not face variations in neurological and cognitive development in ASD as deficits but as normal non-pathological human variations. Thus, ASD is not identified as a neurocognitive pathological disorder that deviates from the typical, but as a neuro-individuality, a normal manifestation of a neurobiological variation within the population.

In this light, neurodiversity is described as equivalent to any other human variation, such as ethnicity, gender, or sexual orientation. This review will provide insights about the neurodiversity approach in children and adults with ASD. Using a neurodiversity approach can be helpful when working with children who have autism spectrum disorder (ASD).

This method acknowledges and values the various ways that people with ASD interact with one another and experience the world in order to embrace the neurodiversity approach when working with children with ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is globally increasing in prevalence. The rise of ASD can be partially attributed to diagnostic expansion and advocacy efforts; however, the interplay between genetic predisposition and modern environmental exposures is likely driving a true increase in incidence. A range of evidence indicates that prenatal exposures are critical. Infection during pregnancy, gestational diabetes, and maternal obesity are established risk factors for ASD. Emerging areas of research include the effects of maternal use of selective serotonin reuptake inhibitors, antibiotics, and exposure to toxicants during pregnancy on brain development and subsequent ASD. The underlying pathways of these risk factors remain uncertain, with varying levels of evidence implicating immune dysregulation, mitochondrial dysfunction, oxidative stress, gut microbiome alterations, and hormonal disruptions. This narrative review assesses the evidence of contributing prenatal environmental factors for ASD and associated mechanisms as potential targets for novel prevention strategies.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis and therapeutic strategies.

To explore the genetic architecture of ASD, elucidate mechanistic insights into genetic mutations, and examine gene-environment interactions.

A comprehensive systematic review was conducted, integrating findings from studies on genetic variations, epigenetic mechanisms (such as DNA methylation and histone modifications), and emerging technologies [including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 and single-cell RNA sequencing]. Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.

Genetic studies have identified numerous risk genes and mutations associated with ASD, yet many cases remain unexplained by known factors, suggesting undiscovered genetic components. Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving. Epigenetic modifications, particularly DNA methylation and non-coding RNAs, also play significant roles in ASD pathogenesis. Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.

Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments. Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice. Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies, ultimately enhancing outcomes for individuals affected by ASD.

Evidence suggests different mismatch negativity (MMN) and P3a responses in individuals with autism spectrum disorder (ASD). Since unaffected siblings shared aberrant neurocognition and brain connectivity with ASD probands, this study investigated MMN and P3a responses in unaffected siblings and explored its neurocognitive implications and effects modifiers. We assessed 43 unaffected siblings of ASD probands and 64 non-autistic comparisons (NTC) using MMN and P3a on both frequency and duration oddball paradigms. The amplitude and latency of MMN and P3a were compared between unaffected siblings and NTC, and validated in 67 ASD probands. In addition, the neurocognitive correlates of MMN and P3a parameters were explored in attention performance, spatial working memory (SWM), and visual research via the tasks of the Conners' Continuous Performance Test and the Cambridge Neuropsychological Test Automated Battery. Compared to NTC, unaffected siblings and ASD probands presented a shorter MMN latency. The P3a amplitude of the duration paradigm (dP3a) was correlated with fewer commission errors, fewer SWM total errors, higher detectability, and more correct responses on visual search tasks. In addition, the dP3a amplitude significantly interacted with sibship, age, and full-scale IQ to predict attention performance, SWM total errors, and total correct response on visual search. Findings suggest that unaffected siblings of ASD may have earlier brain responses upon novelty discrimination. P3a amplitude may correlate with better neurocognitive performance, but the effect was moderated by sibship, age, and intelligence.

Maternal immune activation (MIA) is reported to increase the risk of psychiatric disorders in the offspring. However, the underlying mechanism remains unclear. Methods: We constructed a MIA mouse model by intraperitoneal injection of LPS into pregnant mice and evaluated the behaviors and gene expression profiles in the brains of the female and male offspring, respectively. Results: We found that the MIA female offspring exhibited increased anxiety and a large number of differentially expressed genes (DEGs) in the brain, which were enriched with candidate gene sets of psychiatric disorders and immune functions. In contrast, the MIA male offspring exhibited no significant abnormal behaviors and only a small number of DEGs that were not enriched with disease genes and immune functions. Therefore, we further pursued the downstream study on the molecular mechanism underlying the increased anxiety in the female offspring. We identified the lncRNA AU020206-IRFs-STAT1-cytokine axis by integrating lncRNA-protein interaction data and TF-promoter interaction data, and verified the axis in vitro and in vivo. Conclusion: This study illustrates that MIA upregulates the AU020206-IRFs-STAT1 axis in controlling the brain immunity linked to abnormal behaviors, providing a basis for understanding the role of MIA in psychiatric disorders.

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

Autism spectrum disorders (ASD) can be caused by environmental factors. These factors act early in the development of the nervous system and induce stereotyped repetitive behaviors and diminished social interactions, among other outcomes. Little is known about how these behaviors are produced. In pregnant women, delivery of valproic acid (VPA) (to control seizure activity or stabilize mood) or immune activation by a virus increases the incidence of ASD in offspring. We found that either VPA or Poly Inosine:Cytosine (which mimics a viral infection), administered at mouse embryonic day 12.5, induced a neurotransmitter switch from GABA to glutamate in PV- and CCK-expressing interneurons in the medial prefrontal cortex by postnatal day 10. The switch was present for only a brief period during early postnatal development, observed in male and female mice at postnatal day 21 and reversed in both males and females by postnatal day 30. At postnatal day 90, male mice exhibited stereotyped repetitive behaviors and diminished social interaction while female mice exhibited only stereotyped repetitive behavior. Transfecting GAD1 in PV- and CCK-expressing interneurons at postnatal day 10, to reintroduce GABA expression, overrode the switch and prevented expression of autistic-like behavior. These findings point to an important role of neurotransmitter switching in mediating the environmental causes of autism.