ABSTRACT

The potential etiological and diagnostic values of the gut microbiota in children with neurodevelopmental disorders are encouraging but controversial. In particular, the composition and characteristics of the gut microbiota in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) remain largely unidentified. Herein, we analyzed stool samples from 113 participants with a clinical diagnosis of ASD, 43 with ADHD, 8 with both ASD and ADHD, and 120 healthy controls between 2 and 11 years of age using 16S rRNA sequencing. We observed that clinical diagnosis, age, comorbidities, food sensitivities, and antibiotic use significantly affected the gut microbiota. The enriched genera in the control group were relatively common and dominant human gut bacteria, such as Bacteroides, Faecalibacterium, and Roseburia. The genera present in children with neurodevelopmental disorders showed greater heterogeneity, and the abundance of Bifidobacterium was consistently increased. We found 4899 deregulated microbial metabolic functions and revealed the formation of a divergent genus-level network in patients. This analysis demonstrated that the gut microbial signatures efficiently discriminated patients from healthy participants in both the discovery (area under the curve [AUC]: 0.95–0.98) and validation (AUC: 0.69–0.74) sets. Importantly, although ASD and ADHD share several gut microbial characteristics, specific bacteria that contribute to the disease pathogenesis may have different metabolic functions.

ABSTRACT

In an effort to reduce the “waitlist crisis,” researchers have developed training programs to educate community-based clinicians in best-practice autism diagnostic assessments. This systematic review aims to synthesize the effectiveness and implementation outcomes of such trainings. The following databases were searched from inception until August 2023: PubMed, Web of Science, APA PsycINFO, CINAHL, ERIC, and a select number from Google Scholar. Ten studies were included in the present review because they met the following criteria: development and/or evaluation of a training for practicing community-based clinicians to diagnose autism, published full-text in English, and original research. Risk of bias was assessed through an adapted NIH quality assessment tool. Only seven distinct training programs in autism diagnosis for practicing community-based clinicians were identified. Trainings demonstrated preliminary efficacy in the improvement of clinician knowledge, self-efficacy, practice behavior, and diagnostic accuracy. Many of the trainings had a reported positive impact on the community and were feasible to participate in; however, systems-level factors (e.g., time and reimbursement) remain as barriers to community-based diagnosis. Findings from the present review position clinician training as a promising strategy to increase families' timely access to an autism diagnosis. More research on training models is needed due to both the limited number of trainings and the limited reported effectiveness and implementation outcomes. Future implementation studies are also needed to reduce systems-level barriers and to aid in the determination of what trainings best fit the needs of different contexts.

ABSTRACT

The aim of this study was to investigate differences in mu-wave modulation in individuals diagnosed with autism spectrum disorder (ASD) without intellectual disabilities compared to a group of neurotypical controls (NT). Thirty autistic individuals and 30 NT underwent an EEG recording while watching short videos depicting goal-oriented action filmed from a fixed position, zooming in on the scene, and approaching the scene by means of a steadycam. Then, participants underwent a rating task to evaluate their subjective viewing experience. We found that steadycam videos elicited enhanced event-related desynchronization (ERD), suggestive of enhanced neural activity, in the NT group, and a reduced ERD in the autistic group, compared to the other filming conditions. Autistic participants also showed difficulties in returning to baseline mu-power levels after watching videos filmed from a fixed position. Finally, NT reported feeling more comfortable watching videos with movement, whereas autistic participants did not exhibit differences between conditions. We speculated that static, less naturalistic stimuli might impose higher and prolonged cognitive demands on autistic individuals. Understanding these differences might help develop tailored interventions to support perceptual, cognitive, and social processes of autistic people.

ABSTRACT

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder characterized by atypical brain development. Previous whole-brain BrainAGE studies have unveiled the presence of accelerated or delayed brain function developmental patterns in individuals with ASD. However, it remains unclear whether these patterns manifest at a global level throughout the entire brain or are specific to certain functional sub-networks. The study included resting-state functional magnetic resonance imaging (fMRI) data from 127 individuals with ASD and 135 healthy controls (aged between 5 and 40 years). ALFF maps were measured for each participant. Then, sub-network-level BrainAGE analyses were conducted across 10 sub-networks using the Individual-weighted Multilayer Perceptron Network (ILWMLP) regression method. The BrainAGE analyses revealed atypical developmental trajectories in sensorimotor-related sub-networks, encompassing auditory, motor, and sensorimotor sub-networks. In individuals with ASD, delayed brain function development was observed in the auditory and sensorimotor networks, with a more pronounced delay observed in older individuals. Conversely, the motor network exhibited accelerated development in younger individuals but delayed development in older individuals. Our findings unveiled aberrant developmental patterns in sensorimotor-related sub-networks among individuals with ASD, exhibiting distinct atypical profiles across different sub-networks. These results might contribute to a deeper understanding of the deviant brain development observed in ASD.

ABSTRACT

This study explored waiting times and the factors influencing them in child and adult populations undergoing assessment for autism, ADHD, and other neurodevelopmental differences. The analysis focused on a retrospective review of 408 cases with assessments completed between October 2021 and May 2022, conducted by 30 diagnosing teams in Scotland. Data included age, final diagnosis, demographics, medical and developmental history, contact frequency, and assessment service adherence to best-practice standards. Waiting times were calculated, and relationships were analyzed using linear regression. Median waiting times were 525 days (IQR 329–857) for children/adolescents and 252 days (IQR 106–611) for adults. Only 20% of children's and 47% of adult assessments met the proposed 252-day diagnostic time target. Autism and ADHD were the most common diagnoses. Receiving > 1 neurodevelopmental diagnosis on completion was uncommon. Demographic factors did not significantly affect waiting times. Children/adolescents with more complex developmental and medical histories experienced longer waits (100.3 weeks vs. 67.7 weeks; p < 0.001), while adults with similar histories had shorter waits (32.7 weeks vs. 57.4 weeks; p = 0.016). Adults with ADHD experienced longer waits than autistic adults (63.4 weeks vs. 38.6 weeks, p = 0.002). Adherence to best-practice quality standards was associated with shorter waits for children (β = 0.27, p = 0.002), but the relationship between standard adherence at different stages and for adults was less clear. More frequent appointments correlated with shorter adult waits (33.7 weeks vs. 59.2 weeks, p = 0.015). Gender distribution was balanced among adults, but children's services included more boys. The study highlights long waits and the need for improvement in processes.

ABSTRACT

To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)—an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male–male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social–emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior. These findings advance our mechanistic understanding of the social difficulties characterizing autism.

ABSTRACT

We assessed parent stress and competence outcomes from participation in a randomized controlled trial of a modular behavioral intervention (Modular Approach for Young Autistic Children; MAYAC) compared to a treatment-as-usual comprehensive behavioral intervention (CBI). Throughout their participation, parents of military families were included in their child's treatment (e.g., identifying goals, learning strategies to support their child) and reported on their feelings of stress using the Parenting Stress Index—4, Short Form (PSI-4), as well as their feelings of satisfaction and efficacy as a parent on the Parenting Sense of Competence (PSOC) scale. A linear mixed model evaluated the differences in stress and competence from baseline to each assessment period through follow-up. There were no significant differences between groups in stress or competence ratings; however, there were within-group changes in both treatment arms over the course of the trial. In both groups, parent stress decreased, and competence increased over time, continuing to suggest that behavioral analytic intervention for young children with autism can promote positive parent outcomes.

Trial Registration: ClinicalTrial.gov identifier: NCT04078061

ABSTRACT

Autism spectrum disorder (ASD) is a complex neuro developmental condition characterized by significant genetic and phenotypic variability, making diagnosis and treatment challenging. The heterogeneity of ASD-associated genetic variants and the absence of clear causal factors in many cases complicate personalized care. Traditional models, such as postmortem brain tissue and animal studies, have provided valuable insights but are limited in capturing the dynamic processes and human-specific aspects of ASD pathology. Recent advances in human induced pluripotent stem cell (iPSC) technology have transformed ASD research by enabling the generation of patient-derived neural cells in both two-dimensional cultures and three-dimensional brain organoid models. These models retain the donor's genetic background, allowing researchers to investigate disease-specific cellular and molecular mechanisms while identifying potential therapeutic targets tailored to individual patients. This commentary highlights how stem cell-based approaches are advancing our understanding of ASD and paving the way for more personalized diagnostic and therapeutic strategies.

ABSTRACT

Figurative language, including metaphors and similes, is a crucial component of communication; yet, it presents significant challenges for individuals with autism spectrum disorder (ASD). A critical gap in existing research is the impact of bilingualism on the ability of children with ASD to understand and produce non-literal speech. This study addresses this gap by examining the comprehension and production of metaphors and similes in monolingual and bilingual Greek-speaking children with high-functioning ASD. To the best of our knowledge, this is the first study to investigate these abilities in bilingual children with ASD. Thirty-three monolingual and 18 bilingual children participated in tasks designed to assess comprehension, production, and error patterns for metaphors and similes. The study has also investigated the roles of non-verbal intelligence, language skills (expressive vocabulary), and executive functions (working memory) in the children's performance in the metaphor and simile tasks. Results showed that the two groups did not differ in metaphor comprehension; however, bilingual autistic children with higher non-verbal intelligence appeared to have superior performance in metaphor comprehension compared to their bilingual peers with lower non-verbal intelligence. The bilingual autistic children outperformed their monolingual peers in metaphor production, likely due to their higher non-verbal intelligence ability, despite the fact that the bilingual group had lower expressive vocabulary scores than the monolingual children. Simile comprehension, on the other hand, favored monolingual children, while no significant group differences were observed in simile production. Regarding errors, both groups exhibited similar error patterns, with literal interpretations being the dominant error type across both groups, suggesting that pragmatic language difficulty is a hallmark feature in ASD. The findings challenge the misconception that bilingualism hinders language development in children with ASD and highlight its potential to provide benefits in the realm of non-literal language processing.

ABSTRACT

Gastrointestinal (GI) difficulties are common in children diagnosed with autism spectrum disorder (ASD). However, these difficulties can frequently remain unrecognized. Therefore, we aimed to translate a newly developed instrument, The Autism Spectrum Disorder Gastrointestinal and Related Behaviors Inventory in Children (ASD-GIRBI), to assess its reliability and to explore the frequency of various gastrointestinal difficulties and related behaviors, as well as to explore the association of GI difficulties with the measures of social functioning and emotional and behavioral difficulties in children with ASD. A total of 98 children and adolescents (aged 4–18 [M ^age = 10.67 ± 3.705], 82.7% male), previously diagnosed with ASD at the Institute of Mental Health in Belgrade, Serbia, took part in this research. Their parents filled out the following questionnaires: ASD-GIRBI (an assessment of gastrointestinal and related symptoms), Stanford Social Dimensions Scale (SSDS) (a measure of social functioning) and Strengths and Difficulties Questionnaire (SDQ) (a measure of emotional and behavioral problems). Our results indicate that the ASD-GIRBI is a reliable instrument for GI difficulties assessment (Cronbach's α = 0.841) with the total score successfully discriminating between the participants with and without a GI disorder diagnosis (p = 0.040). Any gastrointestinal symptom was present in 54.1% of the participants, most commonly flatulence, diarrhea, and constipation. The severity of gastrointestinal difficulties correlated to emotional problems (r = 0.261, p < 0.01), conduct problems (r = 0.219, p < 0.05), hyperactivity (r = 0.381, p < 0.01), peer problems (r = 0.266, p < 0.01), total difficulties (r = 0.454, p < 0.01) and total difficulties impact (r = 0.321, p < 0.01). Our data emphasize the potential importance of GI difficulties for various areas of functioning of individuals with ASD.

ABSTRACT

The Psychopathy Checklist Short Version (PCL:SV) is a brief measure of psychopathy. This study aimed to assess the reliability and validity of the PCL:SV with autistic adults detained in inpatient psychiatric care. Data were collected from 282 autistic adults at two time points separated by 12-months. Reliability and validity were investigated using omega, regression, receiver operating characteristic curves, and correlational analysis. PCL:SV Total, Factor 1, and Factor 2 had satisfactory to high reliability and construct validity. Higher PCL:SV scores were associated with poorer treatment progress, a longer length of stay, and previous criminal offending. Factor 1 was associated with a forensic history, detention under Part III of the Mental Health Act, and a personality disorder diagnosis, while Factor 2 was also associated with the absence of a forensic history, detention under Part II of the Mental Health Act, but not a personality disorder diagnosis. It was thought that Factor 2 most likely captured data associated with autism and/or intellectual disabilities (e.g., behaviors that challenge). Those with intellectual disabilities were less likely to have convictions, a history of violent offending, or a forensic history. They were also more likely to be detained under Part II of the Mental Health Act, and were more likely to have had a positive transfer 12-months later to a ward with lesser security. The PCL-SV correlated as expected with the HCR-20 and the START. This study provides preliminary evidence to support the use of the PCL:SV with autistic adults, including those with intellectual disabilities, within inpatient psychiatric hospitals.

ABSTRACT

Sensorimotor impairments are common in autism spectrum disorder (ASD) and evident in unaffected first-degree relatives, suggesting that they may serve as endophenotypes associated with inherited autism likelihood. We tested the familiality of sensorimotor impairments in autism across multiple motor behaviors and effector systems and in relation to parental broader autism phenotypic (BAP) characteristics. Fifty-seven autistic individuals (probands), 109 parents, and 89 neurotypical control participants completed tests of manual motor and oculomotor control. Sensorimotor tests varied in their involvement of rapid, feedforward control and sustained, sensory feedback control processes. Subgroup analyses compared families with at least one parent showing BAP traits (BAP+) and those in which neither parent showed BAP traits (BAP−). Results show that probands with BAP− parents (BAP− probands) showed atypical control of rapid oculomotor behaviors, while BAP+ probands showed impairments of sustained manual motor and oculomotor behaviors compared to controls. BAP− parents showed impaired rapid oculomotor and sustained manual motor abilities relative to BAP+ parents and controls. Rapid oculomotor behaviors were highly intercorrelated among probands and their biological parents. These findings indicate that rapid oculomotor behaviors are selectively impacted in BAP− probands and their parents and may reflect a familial likelihood for autism independent of parental autistic traits. In contrast, sustained sensorimotor behaviors were affected in BAP+ probands and BAP− parents, suggesting separate familial pathways associated with autism. Finally, atypical saccade dynamics may serve as strong endophenotypes for autism. These findings provide new evidence that rapid and sustained sensorimotor alterations represent strong but separate familial pathways of inherited likelihood for autism.

ABSTRACT

Previous research indicates that difficulties with expressing remorse may contribute to the longer sentences autistic individuals receive within the criminal justice system. These differences in remorse expression may stem from their reduced ability to perceive emotions in others. This study investigated the association between an individual's level of autistic traits and their remorse perception ability. We also examined the influence of Affective Theory of Mind (ToM), the ability to understand others' emotional experiences, in remorse perception. We thought that the more autistic traits with which a person presented, the poorer their ability to perceive remorse would be, with overall ToM and affective ToM serving as mediating factors. Forty-five autistic and 47 non-autistic individuals assessed a series of facial expressions to determine the perceived level of remorse in each face. Results revealed that neither the combination of autistic traits nor any individual trait was significantly correlated with remorse perception ability. Additionally, autistic traits did not indirectly impact the perception of remorse through either overall ToM or affective ToM. These findings imply that individuals with high autistic traits, regardless of their perspective-taking abilities, exhibit similar capacities for perceiving remorseful expressions to those with less autistic traits—at least when the stimuli are static. Future research should investigate the differences between autistic and non-autistic individuals in perceiving remorse through different modalities of emotional expression, including behavioral and verbal cues.

Autism Research, Volume 18, Issue 2, Page 231-235, February 2025.

ABSTRACT

Research and clinical work demonstrate that adults with intellectual and developmental disabilities (IDDs; including autistic adults and adults with other IDDs) struggle with key outcomes in adult life, including social relationships, employment, autonomy, and life satisfaction. However, few validated measures exist to measure these outcomes in adults with IDDs. The Relationships, Employment, Autonomy, and Life Satisfaction (REALS) Measures were created using methods developed by the Patient-Reported Outcomes Measurement Information System (PROMIS) to assess these outcomes. Large item pools were generated for the four domains, and, in field testing, 875 adults with IDDs (90% autistic; 18.4% with intellectual disability or a non-autism IDD) and 911 proxy reporters (caregivers; 79% autistic; 48.3% with intellectual disability or a non-autism IDD) completed 108 and 74 items, respectively, using response options capturing frequency, level of support needed, and satisfaction. The structure and item content of the REALS Measures were determined through an iterative process using both classical test theory and item response theory analyses. The final versions include 19 self-report and 14 proxy-report measures, with a range of 3 to 14 items each. The measures have excellent psychometric properties, high precision, and acceptable respondent burden. Thus, they are applicable for service provision, clinical, and research arenas for autistic adults and adults with other IDDs, though additional testing in IDD is warranted and evidence supporting self-report use in IDD is more limited.

ABSTRACT

Parents of autistic children are at a higher risk for mental health problems, including anxiety, depression, and stress. Cognitive behavior therapy (CBT) that targets children's emotion regulation may have an indirect influence on parent outcomes, especially if they play a supporting role in their child's intervention. However, most CBT interventions have been carried out in highly controlled research settings and there are a few studies that examined parental outcomes after participating in autistic child-focused CBT within a community setting. The current study examined parent outcomes (i.e., mental health problems, mindful parenting, and parenting practices) following a community-based CBT program with concurrent parent involvement for autistic children, as well as associations between changes in parent and child outcomes (i.e., autism symptoms and emotion dysregulation). Participants included 77 parent–child dyads across seven community organizations in Ontario, Canada. Parents reported improved mindful parenting and positive parenting practices post-intervention, and no significant changes in their mental health. Multiple mediation analyses revealed that positive changes in parent outcomes (i.e., mindful parenting and parenting practices) were associated with positive changes in child emotion regulation. These positive changes in parenting practices mediated the relationship between mindful parenting and child emotion regulation. Results suggest that participating in community-based CBT is mutually beneficial for autistic children and their parents, particularly in improving parenting behaviors.

ABSTRACT

Central sensitivity syndromes (CSSs) are a group of health conditions thought to include an underlying sensitisation of the central nervous system. Evidence suggests autistic adults experience poorer physical health than the general population and are more likely to have a CSS. This study examined CSS diagnoses and symptoms in autistic and non-autistic adults, to determine whether CSS symptoms were related to autistic traits, mental health, sensory sensitivity, age or gender. Participants included 534 adults with clinical diagnoses of autism, CSS, both diagnoses or neither (i.e., comparison group), who were recruited through social media, support groups and institutional affiliations. Participants completed online self-report validated questionnaires, including the Autism Spectrum Quotient (AQ), Central Sensitization Inventory (CSI), Sensory Perception Quotient (SPQ), and the PHQ-9 and GAD-7. Autistic people without a diagnosed CSS reported significantly more CSS symptoms than the comparison group, with a mean score above the clinical cut-off. Non-autistic participants with a CSS had significantly more autistic traits than the comparison group. Autistic people with a CSS reported the most sensory sensitivity, with autism only and CSS only groups reporting similar levels of sensory sensitivity and all diagnostic groups reporting more sensory sensitivity than the comparison group. Sensory sensitivity, anxiety, autistic traits, age and gender were all significant predictors of CSS symptoms. The overlap in symptoms between autistic individuals and those with CSS suggests diagnostic overshadowing and possible under-diagnosis or misdiagnosis. Furthermore, these symptoms may exacerbate or mask one another. Notwithstanding potential limitations of representativeness and selection bias, increased awareness of the association between autistic traits and CSS symptoms is important for clinicians to improve diagnostic accuracy and treatment.

ABSTRACT

Although autism is a childhood-onset neurodevelopmental disorder, its features change across the life course due to a combination of individual and contextual influences. However, the influence of contextual factors on development during childhood and beyond is less frequently studied than individual factors such as genetic variants that increase autism risk, IQ, language, and autistic features. Potentially important contexts include the family environment and socioeconomic status, social networks, school, work, services, neighborhood characteristics, environmental events, and sociocultural factors. Here, we articulate the benefit of studying contextual factors, and we offer selected examples of published longitudinal autism studies that have focused on how individuals develop within context. Expanding the autism research agenda to include the broader context in which autism emerges and changes across the life course can enhance understanding of how contexts influence the heterogeneity of autism, support strengths and resilience, or amplify disabilities. We describe challenges and opportunities for future research on contextual influences and provide a list of digital resources that can be integrated into autism data sets. It is important to conceptualize contextual influences on autism development as main exposures, not only as descriptive variables or factors needing statistical control.

ABSTRACT

A growing body of literature suggests that youth with autism spectrum disorders (ASD), herein, autistic youth, face an increased risk of being exposed to adverse childhood experiences (ACEs). However, trauma-informed approaches to care among autistic youth remain limited. In a large cross-sectional survey of ASD providers (N = 670) recruited from five U.S. locations, we examined the association between neighborhood resources using the Child Opportunity Index (i.e., educational, health/environmental, and social/economic opportunities) and the frequency at which providers engaged in trauma-informed care (i.e., inquire about, screen for, treat, and provide referrals for trauma diagnosis and treatment) and the types of adverse childhood experiences (ACEs) they screen for (i.e., maltreatment/neglect and household dysfunction). The latent model revealed that providers in neighborhoods with fewer resources engaged in more trauma-informed care and were more likely to screen for ACEs related to household dysfunction. Follow-up exploratory analyses indicated that providers in the lowest 20% of opportunity neighborhoods made the greatest efforts in trauma screening for maltreatment and household dysfunction, followed closely by those in the lowest 40%, compared to higher-opportunity areas. Sensitivity analyses, controlling for potential nesting effects, confirmed similar results. These findings may suggest a concerted effort to ensure that autistic youth in highly disadvantaged areas receive adequate trauma screening. However, lower screening rates in higher-resourced neighborhoods may mean trauma-exposed autistic youth in these areas are overlooked. Expanding provider training to emphasize trauma inquiry across all neighborhoods could help address this gap. Limitations, implications for policy and practice, and future directions are discussed.

ABSTRACT

The present study aimed to evaluate the reliability and validity of the Childhood Autism Rating Scale: Second Edition (CARS2) in diagnosing individuals with autism in Iran. A mixed-method approach was used and 313 participants were recruited, with an age range of 2–32 years, for CARS2-Standard Form (ST) and 218 individuals aged 6–25 years for CARS2-High Functioning (HF). The participants were recruited from daycare centers, schools, and clinics with different developmental trajectories: autism, intellectual disabilities, and neurotypical development. All participants with autism and intellectual disabilities had been clinically diagnosed previously. In addition, the CARS2-Questionnaire of Parent Concerns (QPC) was used to gather qualitative data on 30 randomly selected parents and the perspectives of the 20 test administrators were also collected. The CARS2 had high internal consistency, inter-rater reliability, and test–retest reliability. Factor analyses revealed a one-factor structure for CARS2-ST and a three-factor structure for CARS2-HF. When adjustments were made to the cut-off points, the discriminant analyses indicated that CARS2 effectively differentiated between those with autism and typical development but less so with persons who had intellectual disabilities. The qualitative data analysis and the extracted themes suggest that the CARS2-QPC is a valid tool for collecting autism-related information from parents. Our findings suggest that the CARS2 is broadly a reliable and valid instrument for diagnosing autism spectrum in Iran in the absence of more extensive assessments.

ABSTRACT

Despite substantial evidence linking insomnia with increased suicidality in non-autistic populations, its role in autism remains under-explored. Poor sleep, most commonly insomnia symptoms (hereafter insomnia), is a significant issue in autism, affecting up to 80% of autistic children and adults, compared with 30%–50% of children and about 45% of adults in the general population. Sleep, along with quality of life, anxiety, depression, and social well-being, is a top mental health research priority for autistic adults. These factors are all significantly associated with insomnia in both autistic and non-autistic individuals. Current findings highlight the association between depression, psychosocial factors, and suicidality in autistic individuals. Key factors in suicidality for autistic people include increased autistic traits, loneliness, lack of social support, and experiences such as camouflaging and burnout. What is under-explored is the role of sleep in suicidality and mental health in autism. Effective psychological interventions for insomnia in autistic individuals are lacking, and there is limited understanding of whether treating insomnia can reduce suicidality. Only two pilot studies have investigated insomnia treatments for autistic adults. In this commentary, we argue that, given the high rate of suicidality in autism and the potential role of insomnia, it is crucial to investigate whether insomnia contributes to suicidality in autistic people and if addressing sleep through prevention strategies, supports, and interventions improves outcomes. Collaboration with the autistic community is essential for addressing this knowledge gap and developing effective interventions.

ABSTRACT

Among autistic individuals, a subphenotype of disproportionate megalencephaly (ASD-DM) seen at three years of age is associated with co-occurring intellectual disability and poorer prognoses later in life. However, many of the genes contributing to ASD-DM have yet to be delineated. In this study, we identified additional ASD-DM candidate genes with the aim to better define the genetic etiology of this subphenotype of autism. We expanded the previously studied sample size of ASD-DM individuals ten fold by including probands from the Autism Phenome Project and Simons Simplex Collection, totaling 766 autistic individuals meeting the criteria for megalencephaly or macrocephaly and revealing 154 candidate ASD-DM genes harboring de novo protein-impacting variants. Our findings include 14 high confidence autism genes and seven genes previously associated with DM. Five impacted genes have previously been associated with both autism and DM, including CHD8 and PTEN. By performing functional network analysis, we expanded to additional candidate genes, including one previously implicated in ASD-DM (PIK3CA) as well as 184 additional genes connected with ASD or DM alone. Using zebrafish, we modeled a de novo tandem duplication impacting YTHDF2, encoding an N6-methyladenosine (m⁶A)-mRNA reader, in an ASD-DM proband. Testing zebrafish CRISPR knockdown led to reduced head/brain size, while overexpressing YTHDF2 resulted in increased head/brain size matching that of the proband. Single-cell transcriptomes of YTHDF2 gain-of-function larvae point to reduced expression of Fragile-X-syndrome-associated FMRP-target genes globally and in the developing brain, providing insight into the mechanism underlying autistic phenotypes. We additionally discovered a variant impacting a different gene encoding an m⁶A reader, YTHDC1, in our ASD-DM cohort. Though we highlight only two cases to date, our study provides support for the m⁶A-RNA modification pathway as potentially contributing to this severe form of autism.

ABSTRACT

Of the 1 in 36 individuals in the United States who are diagnosed with autism spectrum disorder, nearly 40% also have intellectual disability (ID). The cortex has been widely implicated in neural processes underlying autistic behaviors as well as intellectual ability. Thus, neuroimaging features such as cortical thickness are of particular interest as a possible biomarkers of the condition. However, neuroimaging studies often fail to include autistic individuals with ID. As a result, there are few studies of cortical thickness in autistic individuals across the entire range of intellectual abilities. This study used MRI to evaluate cortical thickness in young autistic children (n = 88, mean age 5.37 years) with a large range of intellectual ability (IQ 19–133) as well as nonautistic, nondevelopmentally delayed (referred to here as typically developing [TD]) peers (n = 53, mean age 5.29 years). We first investigated associations between full scale IQ and cortical thickness in both autistic and TD children. Autistic children had significant negative associations (i.e., thinner cortex, higher IQ) in bilateral entorhinal cortex, right fusiform gyrus, superior, middle and inferior temporal gyri, and right temporal pole that were not present in TD children. Significantly thicker cortex was also observed in these regions for autistic children with ID (i.e., IQ ≤ 70) compared with those without. Last, given the reported correspondence between the severity of autism symptoms and intellectual ability, we compared cortical thickness associations with both IQ and ADOS Calibrated Severity Scores and found these patterns overlapped to a significant degree across the cortex.

Autism Research, Volume 18, Issue 1, Page 9-16, January 2025.

Autism Research, Volume 18, Issue 1, Page 1-6, January 2025.

Autism Research, Volume 18, Issue 2, Page 236-237, February 2025.

ABSTRACT

Catatonia is a highly morbid psychomotor and affective disorder, which can affect autistic individuals with and without intellectual disability. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments in autistic individuals has not been described. We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024. Data investigating pharmacologic interventions, and clinical measures including the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), Kanner Catatonia Examination (KCE), and Clinical Global Impression—Improvement (CGI-I) were collected. Forty-five autistic patients with co-morbid catatonia were treated during the study period. The mean age was 15.6 (SD = 7.9) years [Mdn = 16.0, range 6.0–31.0]. Forty-one patients (91.1%) met criteria for autism with co-occurring intellectual disability. All patients received pharmacotherapy. Forty-four (97.8%) were treated with benzodiazepines with a mean maximal daily dose of 17.4 mg (SD = 15.8) lorazepam equivalents. Thirty-five patients (77.8%) required more than one medication class for treatment. Sixteen (35.6%) patients received electroconvulsive therapy. Fourteen patients (31.1%) attempted to taper off benzodiazepines after achieving clinical improvement during the study period; of these, 5 patients (11.1%) were successfully tapered off, and the remaining 9 (17.8%) discontinued the taper due to a return of catatonic symptoms. Statistically significant improvement was observed across all clinical domains except the KCS. However, the majority remained at least partially symptomatic over the study period. Three patients (6.7%) died over the study period. Despite clinical improvements while receiving the gold standard for psychopharmacologic management of catatonia, chronic symptoms remained for the majority of catatonia patients over the study period, and few were able to taper and discontinue benzodiazepine treatment. Notably, the open label design of this study is a limiting factor when interpreting the results.

Autism Research, Volume 18, Issue 1, Page 7-8, January 2025.

ABSTRACT

This study explored gross motor development (GMD) trajectories among 6359 children, with and without autism, from the Growing Up in New Zealand longitudinal cohort study. By the age of 8, 173 children had either an autism diagnosis (n = 108) or parent-reported autism concerns (n = 65). Gross motor milestones were reported by mothers when children were 9, 24, and 54 months of age. We found that irrespective of autism diagnosis, GMD delays at 24 months of age were more likely among girls, children born preterm, and those whose mothers identified as European. A mixed-effect logistic regression model, controlling for antenatal maternal and child covariates, revealed that the proportion of children with GMD delay (relative to their peers) increased significantly from 9 to 54 months for all three groups, but the increase was greater for those with autism concerns (OR = 1.28, 95% CI = 1.08–1.52) or an autism diagnosis (OR = 1.26, 95% CI = 1.10–1.43) compared to the no autism group (OR = 1.06, 95% CI = 1.02–1.10). Differences in the changes in GMD performance among children with an autism diagnosis compared to those without autism occurred between 9 and 24 months (OR = 2.16, 95% CI = 1.13–4.13). No significant GMD delay differences were found at any time between children with an autism diagnosis versus those with autism concerns. Children with a GMD delay should be screened for autism at 24 m. Early identification is the first step toward knowledge-based, effective intervention of developmental difficulties.

ABSTRACT

Neurodevelopmental disorders (NDDs) encompass a group of conditions that impact brain development and function, exhibiting significant genetic and clinical heterogeneity. NAA15, the auxiliary subunit of the N-terminal acetyltransferase complex, has garnered attention due to its association with NDDs. However, the precise role of NAA15 in cortical development and its contribution to NDDs remain elusive. By employing targeted sequencing on a large Chinese cohort affected by ASD and conducting an extensive literature review, we have compiled 64 distinct variants in the NAA15 gene identified among individuals with neurodevelopmental disorders. Our research demonstrates that loss of NAA15 leads to a substantial increase in neuronal count, potentially resulting in aberrant brain development and triggering repetitive as well as anxious behaviors in mice models. Furthermore, disorder-associated variants within NAA15 impair axon and synapse formation processes crucial for neural connectivity establishment. These findings shed light on the consequences of NAA15 deficiency along with its de novo mutations on brain development while unraveling the cellular mechanisms underlying NDDs.

ABSTRACT

Prevalence of autism diagnosis has historically differed by demographic factors. Using data from 8224 participants drawn from the Environmental influences on Child Health Outcomes (ECHO) Program, we examined relationships between demographic factors and parent-reported autism-related traits as captured by the Social Responsiveness Scale (SRS; T score > 65) and compared these to relations with parent-reported clinician diagnosis of ASD, in generalized linear mixed effects regression analyses. Results suggested lower odds of autism diagnosis, but not of SRS T > 65, for non-Hispanic Black children (adjusted odds ratio [OR] = 0.76, 95% CI 0.55, 1.06) relative to non-Hispanic White children. Higher maternal education was associated with reduced odds of both outcomes (OR = 0.73, 95% CI 0.51, 1.05 for ASD autism diagnosis and 0.4, 95% CI 0.29, 0.55 for SRS score). In addition, results suggested a lower likelihood of autism diagnosis but a higher likelihood of an SRS score > 65 in Black girls. Findings suggest lower diagnostic recognition of autism in non-Hispanic Black children, despite a similar degree of SRS-assessed autism-related traits falling in the clinically elevated range. Further work is needed to address this disparity.

ABSTRACT

Echolalia, the immediate or delayed repetition of speech, is a core diagnostic criterion for autism spectrum disorder. It has been studied for over 50 years and is well-described; however, no consensus on prevalence estimates exists for echolalia's occurrence in autistic youth. The current study sought to (1) describe endorsement of echolalia-related items using parent-, teacher-, and clinician-reports in a well-validated sample of autistic youth and (2) characterize relations between echolalia and other key factors, including age, language ability, and repetitive behaviors. Participants (n = 2555, 4–17 years, 13% female, 78% White) from the Simon Simplex Collection provided data from multi-informant ratings of echolalia and related behaviors. Nine parent-, clinician-, and teacher-report items were extracted from five measures to broadly capture echolalia through a composite score. Results indicated that as many as 90% of autistic individuals express echolalia at some point in their development. Hierarchical linear regression was conducted to evaluate relations between echolalia, verbal ability, and repetitive behaviors, controlling for age, sex, and autism severity. Results indicated the main effects of verbal ability and repetitive behaviors. A significant interaction qualified this main effect wherein age was negatively associated with echolalia for children with higher verbal ability, but not those with lower verbal ability, suggesting that adolescents with less generative speech may leverage echolalia as a communicative strategy. Echolalia was positively associated with repetitive behaviors across development. These associations support a dualistic interpretation of echolalia as functional communication and as a form of repetitive behavior. Future research is needed to understand the developmental trajectories of echolalia and develop affirming support for this autistic behavior.

Abstract

Children with autism spectrum disorder (ASD) display a variety of core and co-occurring difficulties in social, communication, everyday functioning, cognitive, motor, and language domains. Receiving a combination of services to accommodate needs of autistic individuals is essential for improving their future outcomes. During the COVID-19 pandemic, reduced service access negatively impacted autistic children's outcomes. This study aimed to examine the relationship between service receipt and parental perceived outcomes in autistic children while accounting for various demographic, child, and parental factors. We utilized parental COVID-19 impact survey data from the SPARK study (N = 6067). Ordinal logistic regression analyses were used to predict perceived child outcomes. Demographic, child, and parental factors were included in the prediction models. Service receipt of SLT, ABA, PT/OT, MED, and MH were associated with perceived child outcomes. PT/OT and ABA predicted improvements in domains of social interaction, everyday activity, and overall autism severity; SLT and ABA contributed to improved perceived communication outcomes. Receiving MH and MED services was associated with worsening of perceived outcomes on all domains. Younger age, males, higher family income, lower autism severity, lower motor, function, and cognitive delay, greater language delay, and the absence of parental mental health issues were associated with greater improvements in various perceived outcomes. Overall, PT/OT and ABA services are associated with improved perceived social and functional outcomes whereas SLT and ABA services are associated with improved perceived communication outcomes. We also provide a wholistic view of factors affecting relationships between service receipt and perceived child outcomes during the pandemic.

Abstract

The cerebellum plays a crucial role in functions, including sensory-motor coordination, cognition, and emotional processing. Compared to the neocortex, the human cerebellum exhibits a protracted developmental trajectory. This delayed developmental timeline may lead to increased sensitivity of the cerebellum to external influences, potentially extending the vulnerability period for neurological disorders. Abnormal cerebellar development in individuals with autism has been confirmed, and these atypical cerebellar changes may affect the development of the neocortex. However, due to the heterogeneity of autism spectrum disorder (ASD), the regional changes in the cerebellum and cerebellocerebral structural relationship remain unknown. To address these issues, we utilized imaging methods optimized for the cerebellum and cerebrum on 817 individuals aged 5–18 years in the ABIDE II dataset. After FDR correction, significant differences between groups were found in the right crus II/VIIB and vermis VI-VII. Structural covariance analysis revealed enhanced structural covariance in individuals with autism between the cerebellum and parahippocampal gyrus, pars opercularis, and transverse temporal gyrus in the right hemisphere after FDR correction. Furthermore, the structural covariance between the cerebellum and some regions of the cerebrum varied across sexes. A significant increase in structural covariance between the cerebellum and specific subcortical structures was also observed in individuals with ASD. Our study found atypical patterns in the structural covariance between the cerebellum and cerebrum in individuals with autism, which suggested that the underlying pathological processes of ASD might concurrently affect these brain regions. This study provided insight into the potential of cerebellocerebral pathways as therapeutic targets for ASD.

ABSTRACT

Autistic children are frequently said to speak with accents that markedly differ from those of their linguistic communities. To date, these anecdotal reports have never been tested or explained. We ran two perception studies using short audio recordings of autistic and typically developing children from the Campania region in Italy. The variety of Italian to which children are exposed in this region markedly differs from those spoken in the rest of Italy. Participant responses about the children's geographical origin show: (a) That autistic children's accent is devoid of the regional features of their community; (b) resembles the standard variety used in cartoons and child television programs. The judgments about children's accents are, furthermore, independent of the overall perception of speech atypicality. This paper shows that the accent of autistic children may diverge from that of their caregivers and peers because of the lasting influence of non-interactional, screen sources on their speech.

ABSTRACT

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder and its underlying neuroanatomical mechanisms still remain unclear. The scaled subprofile model of principal component analysis (SSM-PCA) is a data-driven multivariate technique for capturing stable disease-related spatial covariance pattern. Here, SSM-PCA is innovatively applied to obtain robust ASD-related gray matter volume pattern associated with clinical symptoms. We utilized T1-weighted structural MRI images (sMRI) of 576 subjects (288 ASDs and 288 typically developing (TD) controls) aged 7–29 years from the Autism Brain Imaging Data Exchange II (ABIDE II) dataset. These images were analyzed with SSM-PCA to identify the ASD-related spatial covariance pattern. Subsequently, we investigated the relationship between the pattern and clinical symptoms and verified its robustness. Then, the applicability of the pattern under different age stages were further explored. The results revealed that the ASD-related pattern primarily involves the thalamus, putamen, parahippocampus, orbitofrontal cortex, and cerebellum. The expression of this pattern correlated with Social Response Scale and Social Communication Questionnaire scores. Moreover, the ASD-related pattern was robust for the ABIDE I dataset. Regarding the applicability of the pattern for different age stages, the effect sizes of its expression in ASD were medium in the children and adults, while small in adolescents. This study identified a robust ASD-related pattern based on gray matter volume that is associated with social deficits. Our findings provide new insights into the neuroanatomical mechanisms of ASD and may facilitate its future intervention.