Features Of Autism Spectrum Disorder Research Articles

Impaired brainstem auditory evoked potentials after in utero exposure to high dose paracetamol exposure

Paracetamol is an analgesic and antipyretic medication regarded as the safest over-the-counter pain and fever relief option during pregnancy. Paracetamol and its metabolites are known to reach the developing fetus through direct placental transfer and can cross the blood brain barrier. Several recent, large-scale epidemiologic studies suggest that in utero paracetamol exposure can increase the risk of neurodevelopmental conditions, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and developmental delay (DD). Since auditory processing deficits are a common feature of ASD, we hypothesized that animals exposed to paracetamol in utero will have impaired auditory brainstem function. We investigated this hypothesis by recording and analyzing click-evoked auditory brainstem responses (ABR) at postnatal day 21 and 29 in Sprague-Dawley rats. In utero exposure to high dose paracetamol exposure had no impact on body or brain weight. However, high dose paracetamol exposure did significantly delay ear opening and resulted in elevated ABR thresholds, and longer wave and interwave latencies. These changes in wave latency extended to the highest click intensity tested but were most severe near threshold. This data suggests that development and function of the auditory brainstem may be impacted by high dose paracetamol exposure and that simple, non-invasive tests of auditory function have utility as an early screening tool for neurodevelopmental disorders.

Prevalence, incidence, and characteristics of autism spectrum disorder among children in Beijing, China.

It is the first study to explore the prevalence, incidence, and co-occurring conditions of autism spectrum disorder for the preschoolers in China. The prevalence and incidence of autism spectrum disorder has increased in recent decades. Autism spectrum disorder has become an important public concern worldwide. In this study, all hospital confirmed cases had an associated diagnosis (International Classification of Diseases, 10th revision (ICD-10) codes: F84.0, 84.5, F84.9). In total, 4457 children aged 4-6 years were identified as having autism spectrum disorder. In 2021, 1 in 95 children aged 6 years, 1 in 115 children aged 5 years, and 1 in 130 children aged 4 years were estimated to have autism spectrum disorder in Beijing. The incidence was 0.11% in 2019 and increased to 0.18% in 2021. There has been a great emphasis on the importance of early autism spectrum disorder diagnosis in large cities in China.

Monoallelic loss-of-function variants in GSK3B lead to autism and developmental delay.

De novo variants adjacent to the canonical splicing sites or in the well-defined splicing-related regions are more likely to impair splicing but remain under-investigated in autism spectrum disorder (ASD). By analyzing large, recent ASD genome sequencing cohorts, we find a significant burden of de novo potential splicing-disrupting variants (PSDVs) in 5048 probands compared to 4090 unaffected siblings. We identified 55 genes with recurrent de novo PSDVs that were highly intolerant to variation. Forty-six of these genes have not been strongly implicated in ASD or other neurodevelopmental disorders previously, including GSK3B. Through international, multicenter collaborations, we assembled genotype and phenotype data for 15 individuals with GSK3B variants and identified common phenotypes including developmental delay, ASD, sleeping disturbance, and aggressive behavior. Using available single-cell transcriptomic data, we show that GSK3B is enriched in dorsal progenitors and intermediate forms of excitatory neurons in the developing brain. We showed that Gsk3b knockdown in mouse excitatory neurons interferes with dendrite arborization and spine maturation which could not be rescued by de novo missense variants identified from affected individuals. In summary, our findings suggest that PSDVs may play an important role in the genetic etiology of ASD and allow for the prioritization of new ASD candidate genes. Importantly, we show that genetic variation resulting in GSK3B loss-of-function can lead to a neurodevelopmental disorder with core features of ASD and developmental delay.

Neuro-Architecture in Service of the Autism Spectrum: Designing a School Complex Adapted to Autistic Children in Northern Cameroon

This research explores the application of neuro-architecture in the design of a school complex adapted for autistic children in the northern region of Cameroon. The literature review highlights the specific characteristics of autism spectrum disorders (ASD) and the particular sensory needs of children with this condition in an educational setting. It analyzes how architecture, through the management of light, colors, materials, and spatial arrangement, can positively influence the well-being and learning of these children. By integrating the principles of neuro-architecture, the design of optimized school spaces can help reduce sensory overload and improve the social and educational inclusion of autistic children. This review also examines international case studies and potential adaptations to the geographic and cultural context of northern Cameroon, which is characterized by a lack of suitable educational infrastructure. The objective of this research is to propose architectural design solutions that meet the specific needs of autistic children while considering local constraints.

Early gesture development as a predictor of autism spectrum disorder in elevated-likelihood infants of ASD

BackgroundGesture difficulties have been reported in later-born siblings of children with autism spectrum disorder (ASD). Careful observation of gesture development during the first two years of children at elevated likelihood (EL) of developing ASD may identify behavioral indicators that facilitate early diagnosis.MethodsThis study enrolled 47 EL infants and 27 low-likelihood (LL) infants to explore gesture developmental trajectories and the predictive value of gesture to expedite the early detection of core characteristics of ASD. Gesture frequency, communication function, and integration ability were observed and coded from a semi-structured assessment administered longitudinally across 9–19 months of age. We conducted the Autism Diagnostic Observation Schedule assessment at 18–19 months for ASD’s core characteristics.ResultsThe development of joint attention (JA) gestures was slower in the EL than in the LL group. The trajectories of the two groups began to diverge at 14–18 months. Children who reached the diagnostic cutoff point for ASD showed reductions in social interaction gestures at 12–13 months, in gestures integrated with any two communication skills (G-M) at 15–16 months; and in gestures integrated with eye contact (G-E) at 18–19 months. Overall gesture and G-M integration were associated with an overall ADOS communication and social interaction score.ConclusionsThe developmental trajectories of JA gestures of EL and LL children differed. G-M gestures represent early indicators that may be a predictor of ASD.

Frequency and Mental Health Condition of Students with Developmental Disabilities Among First-Year Japanese University Students: A Cross-Sectional Survey.

Students with developmental disabilities are anxious about a change in environment when graduating from high school to college. Existing research, which is scarce, focuses on the mental health status of students with developmental disabilities entering university. This study investigated the frequency of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) among first-year Japanese university students and their mental health risks post-admission. We conducted a cross-sectional survey for university students within a month of admission, using the Autism Spectrum Quotient (AQ) and Adult ADHD Test (A-ADHD) to demonstrate the frequency of ASD and ADHD. The Counseling Center Assessment of Psychological Symptoms (CCAPS)-Japanese (depression, eating concerns, hostility, social anxiety, family distress, alcohol use, generalized anxiety, and academic distress) evaluated their mental health condition.Of 711 students (20.3 ± 2.1years; 330 male, 381 female), the number of those showing either ASD or ADHD tendencies was 61 (8.58%). Twenty-three (3.23%) showed symptoms of only ASD, 34 (4.78%) of ADHD, and four (0.56%) of ASD and ADHD. No significant differences existed in the frequency of ASD and ADHD between each sex and major. The scores and frequency of high risk (over the cut-off points) students on all CCAPS-Japanese subscales (except alcohol use) were significantly higher among the ASD and ADHD groups than the control group, which showed no ASD or ADHD tendencies. The frequency of ASD and ADHD characteristics among first-year Japanese university students was 8.58%. They have a high risk of mental health problems when they enter university.

The role of cerebellar FOXP1 in the development of motor and communicative behaviors in mice.

The gene FOXP2 is well established for a role in human speech and language; far less is known about FOXP1. However, this related gene has also been implicated in human language development as well as disorders associated with features of autism spectrum disorder (ASD). FOXP1 protein expression has also recently been identified in the cerebellum-a neural structure previously shown to express FOXP2 protein. The current study sought to elucidate the behavioral implications of a conditional knock-out of Foxp1 using an En1-Cre driver, which is active in the entirety of the cerebellum and a subset of neurons in the midbrain and spinal cord, in mice using a test battery including motor tasks associated with cerebellar dysfunction, as well as communicative and autistic-relevant behaviors. Male and female mice with a conditional knock-out (cKO, n = 31) and wildtype littermate controls (WT, n = 34) were assessed for gross and orofacial motor control, motor-coordination learning, locomotion, social behavior, anxiety, auditory processing and expressive vocalizations. Overall results suggest Foxp1 plays a specific role in the development of communicative systems, and phenotypic expression of disruptions may interact with sex. Robust motor deficits associated with Foxp1 protein loss may particularly affect vocalizations based on significant orofacial motor deficits in cKO subjects could also contribute to vocalization anomalies. In summary, the current study provides key insights into the role of Foxp1 in cerebellar function and associated behaviors in mice, with implications for an improved understanding of communicative and motor-based neurodevelopmental disabilities in humans.

Early life seizures and olfactory communication in rats.

Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats. KA-induced seizures or saline was administered. Rats were then exposed to a series of biologically relevant scents including male scent, female scent, nest scent, and phenylethylamine during the juvenile period and again during adulthood. Alterations in sensory modalities were expected to be expressed via abnormal preference for certain scents and/or production of abnormal ultrasonic vocalizations in response to scents. The olfactory bulbs were also assessed for the biologically relevant markers glial fibrillary acidic protein (GFAP) and calcium/calmodulin-dependent protein kinase II (CAMKII). Our findings resulted in no significant differences in olfactory preference following ELS for juveniles or adults compared to controls. Similarly, there were no differences in GFAP expression or the ratio of phosphorylated CAMKII to CAMKII in either olfactory bulb. Interestingly, despite a lack of treatment differences, different scents were shown to elicit different responses in juvenile rats, yet these differences subsided in adulthood. Overall, the results of this study suggest that olfaction does not contribute to socialization deficit following ELS within the KA model.

Serum cholesterol in children with ASD

Objectives. Because the brain contains one-quarter of all cholesterol in the body, cholesterol has a significant effect on the brain. Cholesterol may also have an impact on autism, which is associated with poor brain development. Damage to neurons can lead to the emergence of autism spectrum disorders (ASD). This is a case-control study conducted to explore the potential association between serum cholesterol level and ASD in children’s patients. Material and methods. It involved collecting data from medical records, performing interviews, and taking blood samples from patients and a control group of children. The samples consisted of 60 child patients with ASD and an equal number of controls, for a total of 120 participants. Outcomes. There was a significant inverse relationship between cholesterol levels and ASD. The children diagnosed with ASD displayed significantly lower cholesterol levels when compared to healthy children (p-value = 0.004). The age distribution of the participants showed a non-significant difference between the ASD patient group and the control group (p-value = 0.085). This supports the existing knowledge that ASD is more common in children under the age of 18. Conclusions. Children with ASD had a lower total serum cholesterol level than healthy children. This may suggest that there is an inverse relationship between serum cholesterol levels and disease state in children diagnosed with ASD who have lower cholesterol levels. Also, significant differences of gender and BMI were found among study groups, suggesting their association with the disease’s development and consequences. The results of the study also highlight some significant differences in the main basic characteristics of ASD in patients, evaluating their possible roles with the disease’s roots and with serum cholesterol, on the other hand. These findings contribute to a deeper understanding of the sophisticated relationship between cholesterol level and ASD development, potentially opening up new ways for the update of intervention, treatment, and follow-up strategies.

Immune signature of gene expression pattern shared by autism spectrum disorder and Huntington's disease

Autism spectrum disorder (ASD) and Huntington's disease (HD) are complex neurological conditions with unclear causes and limited treatments, affecting individuals, families, and society. Despite ASD and HD representing two opposing stages of neuronal development and degeneration, they share similar clinical-pathological features in motor function. In this study, we leveraged transcriptomic data from the prefrontal cortex available in public databases to identify shared transcriptional characteristics of ASD and HD. Differential expression analysis revealed that the majority of differentially expressed genes (DEGs) were up-regulated in ASD carriers, whereas most DEGs were down-regulated in HD carriers. Among the DEGs shared between both diseases, three out of seven protein-coding genes were related to the immune system. Furthermore, we identified two enriched pathways shared between ASD and HD DEGs. The gene interaction network analysis unveiled four hub genes shared by both diseases, all of which are associated with immune functions. The findings suggest a shared gene expression pattern in the prefrontal cortex of people with ASD and HD, closely linked to the immune system. These findings will contribute to exploring the biological mechanisms underlying the shared phenotypes of these two diseases from an immunological perspective.

Strategies for Assessing Autistic-Like Behaviors in Mice.

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

Amelioration of social impairments in autism: Possible role of vagal afferent stimulation in modification of the prefrontal-amygdala connectivity

Impairment in social interactions is a prominent feature of autism spectrum disorder (ASD). The present hypothesis explains the possible role of vagal afferent stimulation in the modification of prefrontal-amygdala connectivity in the amelioration of social impairments in ASD. Currently, there is no definitive treatment for ASD. However, there is documented evidence showing that interventions that increase vagal tone lead to the improvement of autism-related social symptoms. However, the exact mechanism that explains the correlation between the elevation of vagal tone and the amelioration of autism-related symptoms has not been elucidated. In the present hypothesis, it is proposed that the increase in vagal tone affects the nucleus tractus solitarius (NTS) in the brainstem. The NTS has strong connections with other brainstem nuclei, such as the locus coeruleus and dorsal raphe nucleus. The aforementioned nuclei are the main sources of norepinephrine and serotonin, with extensive projections to various brain areas, especially the prefrontal cortex (PFC) and amygdala. PFC-amygdala functional connectivity plays an important role in social behavior and emotion regulation. Therefore, visceral stimulation, which subsequently increases the vagal tone, possibly leads to the improvement of autistic social deficits through the enhancement of PFC-amygdala functional connectivity. Further investigations are needed to evaluate the function of the mentioned neural pathways during visceral stimulation in individuals with ASD.

Where do neurodevelopmental conditions fit in transdiagnostic psychiatric frameworks? Incorporating a new neurodevelopmental spectrum.

Features of autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disorders, intellectual disabilities, and communication and motor disorders usually emerge early in life and are associated with atypical neurodevelopment. These "neurodevelopmental conditions" are grouped together in the DSM-5 and ICD-11 to reflect their shared characteristics. Yet, reliance on categorical diagnoses poses significant challenges in both research and clinical settings (e.g., high co-occurrence, arbitrary diagnostic boundaries, high within-disorder heterogeneity). Taking a transdiagnostic dimensional approach provides a useful alternative for addressing these limitations, accounting for shared underpinnings across neurodevelopmental conditions, and characterizing their common co-occurrence and developmental continuity with other psychiatric conditions. Neurodevelopmental features have not been adequately considered in transdiagnostic psychiatric frameworks, although this would have fundamental implications for research and clinical practices. Growing evidence from studies on the structure of neurodevelopmental and other psychiatric conditions indicates that features of neurodevelopmental conditions cluster together, delineating a "neurodevelopmental spectrum" ranging from normative to impairing profiles. Studies on shared genetic underpinnings, overlapping cognitive and neural profiles, and similar developmental course and efficacy of support/treatment strategies indicate the validity of this neurodevelopmental spectrum. Further, characterizing this spectrum alongside other psychiatric dimensions has clinical utility, as it provides a fuller view of an individual's needs and strengths, and greater prognostic utility than diagnostic categories. Based on this compelling body of evidence, we argue that incorporating a new neurodevelopmental spectrum into transdiagnostic frameworks has considerable potential for transforming our understanding, classification, assessment, and clinical practices around neurodevelopmental and other psychiatric conditions.

Understanding anxiety‐related problems of children with ASD in school settings

AbstractThe primary purpose of this current study was to identify knowledge of special education and mental health professionals in anxiety‐related problems of children with autism spectrum disorder (ASD) in four Different Categories: Separation Anxiety (SA), Uncertainty (U), Performance Anxiety (PA), and anxiety Arousal (AA). Three hundred eighteen participants across the United States (199 special education teachers, 97 school counselors, and 22 school psychologists) participated. The finding indicated that special education teachers and school counselors have significantly less training and expertise to identify anxiety symptoms in typically developing children and children with ASD than school psychologists (p < .05). Moreover, school counselors have significantly limited knowledge in identifying and treating anxiety issues in children with ASD (p < .05). Findings showed that school counselors could not determine precisely whether symptoms of uncertainty events existed because of anxiety issues or ASD characteristics. School psychologists and special education teachers identified the uncertainty of children with ASD as characteristics of children with ASD, not anxiety symptoms. Implications were discussed.

Sharing Our World: Impact of Group Motor Skill Learning on Joint Attention in Children with Autism Spectrum Disorder.

Impaired joint attention is a common feature of autism spectrum disorder (ASD), affecting social interaction and communication. We explored if group basketball learning could enhance joint attention in autistic children, and how this relates to brain changes, particularly white matter development integrity. Forty-nine autistic children, aged 4-12 years, were recruited from special education centers. The experimental group underwent a 12-week basketball motor skill learning, while the control group received standard care. Eye-tracking and brain scans were conducted. The 12-week basketball motor skill learning improved joint attention in the experimental group, evidenced by better eye tracking metrics and enhanced white matter integrity. Moreover, reduced time to first fixation correlated positively with decreased mean diffusivity of the left superior corona radiata and left superior fronto-occipital fasciculus in the experimental group. Basketball-based motor skill intervention effectively improved joint attention in autistic children. Improved white matter fiber integrity related to sensory perception, spatial and early attention function may underlie this effect. These findings highlight the potential of group motor skill learning within clinical rehabilitation for treating ASD.

Addressing Sensory Challenges in Athletes with Autism Spectrum Disorder: A Clinical Commentary.

Athletes with autism spectrum disorder (ASD) experience lesser care for injuries and athletic trainers (ATs) report feeling unprepared to provide care competently for this population. Provision of sports-related care can be impacted by sensory differences associated with ASD such as hyper-reactivity to sensation or poor integration of sensory information. An in-depth review of the literature using the Strength of Recommendation Taxonomy (SORT) guidelines was used to identify articles that address the sensory features of autism for athletic trainers with the purpose of informing athletic trainers about the sensory features of ASD and to present the most current evidence-based recommendations for providing care to athletes with ASD and other neurodivergent individuals who present with sensory differences. Relevant articles were reviewed by four independent researchers and organized by theme. Key themes included use of sensory friendly or adapted environments, sensory kits, and informed communication strategies that acknowledge sensory differences. Providing individualized care for athletes with ASD and sensory features can improve the quality of and participation in sports for autistic persons.

Characterizing associations between emotion dysregulation, anxiety, and repetitive behaviors in autistic youth with intellectual disability.

There is a paucity of research that explores associations between emotion dysregulation and the expression and severity of core and co-occurring characteristics of autism spectrum disorder (ASD), especially in autistic youth with co-occurring intellectual disability (ID). This study explored the interplay between developmental characteristics and emotion dysregulation, anxiety, and specific subtypes of RRBs that are elevated in autistic youth with co-occurring ID. Generalized additive models demonstrated that age, sex, language level, dysregulation, and anxiety showed unique patterns of association with subtypes of RRBs in a sample of 150 autistic youth with co-occurring ID who are non-speaking or minimally verbal. More specifically, higher anxiety levels were significantly associated with elevations in repetitive sensory motor behaviors (RSMB), self-injurious behaviors (SIB), insistence on sameness (IS), and unusual interests (UI). While emotion dysregulation was a significant predictor of UI, it demonstrated positive, albeit not significant, associations with the intensity of SIB and RSMB. Language level was a significant predictor of RSMB, such that the intensity of RSMB was higher for individuals who were non-speaking relative to those who spoke in single words. These findings provide preliminary insights into patterns of associations between emotion dysregulation, anxiety, and specific subdomains of RRBs in autistic youth with ID.

Experimentally altering microRNA levels in embryos alters adult phenotypes

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, a low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally in mice with two of them, miR19a-3p and miR499a-5p by microinjecting into zygote pronuclei either the complementary sequence or an excess of the microRNA. Both resulted in low levels in the tissues and sperm of the targeted microRNAs and their pri and pre precursors. This method stably modify predetermined levels of miRNAs and identify miRNA alterations that cause changes in autistic behavior and predispose the individual to an inherited disease. Excess miRNA results in single-stranded miRNA variations in both free and DNA-bound RNA (R-loop) fractions in mouse models thus appearing to affect their own transcription. Analysis of miRNAs fractions in human patients blood samples confirm low level of six microRNAs also in R-loop fractions.

Delving into the Complexity of Valproate-Induced Autism Spectrum Disorder: The Use of Zebrafish Models.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition with several identified risk factors, both genetic and non-genetic. Among these, prenatal exposure to valproic acid (VPA) has been extensively associated with the development of the disorder. The zebrafish, a cost- and time-effective model, is useful for studying ASD features. Using validated VPA-induced ASD zebrafish models, we aimed to provide new insights into VPA exposure effects during embryonic development and to identify new potential biomarkers associated with ASD-like features. Dose-response analyses were performed in vivo to study larval phenotypes and mechanisms underlying neuroinflammation, mitochondrial dysfunction, oxidative stress, microglial cell status, and motor behaviour. Wild-type and transgenic Tg(mpeg1:EGFP) zebrafish were water-exposed to VPA doses (5 to 500 µM) from 6 to 120 h post-fertilisation (hpf). Embryos and larvae were monitored daily to assess survival and hatching rates, and numerous analyses and tests were conducted from 24 to 120 hpf. VPA doses higher than 50 µM worsened survival and hatching rates, while doses of 25 µM or more altered morphology, microglial status, and larval behaviours. VPA 50 µM also affected mRNA expression of inflammatory cytokines and neurogenesis-related genes, mitochondrial respiration, and reactive oxygen species accumulation. The study confirmed that VPA alters brain homeostasis, synaptic interconnections, and neurogenesis-related signalling pathways, contributing to ASD aetiopathogenesis. Further studies are essential to identify novel ASD biomarkers for developing new drug targets and tailored therapeutic interventions for ASD.

Picturing immediate echolalia within the context of autism: Examining its formats, actions and patterns under conversation analysis

ABSTRACT Echolalia, a prevalent feature of Autism Spectrum Disorders (ASD), has been extensively debated among behaviourists and developmental researchers for decades, long segmenting clinical work within the context of autism. This qualitative study aimed to explore the interactive underpinnings of immediate echolalia naturally occurring in dyadic conversation between autistic individuals and clinicians, employing turn-by-turn and sequence-by-sequence analysis within the framework of Conversation Analysis (CA). The results revealed that varying the complete-incomplete-transformed format, echolalia helped participants a) express their emotions, b) automatically associate conversation, c) organise their response, d) maintain conversational reciprocity, and e) assist with request initiation. Within the context of echolalia, the dynamics of conversation exhibited blocking, diverting, or affiliating patterns. The current study provides insights into the interactive traits of immediate echolalia and underscores the potential utility for clinical therapists to employ the echoic sources in clinical intervention.