Severe Autism Research Articles

Characterization and Outcomes of Profoundly and Non-profoundly Autistic Individuals Admitted to a Specialized Psychiatric Inpatient Unit.

The prevalence of autism spectrum disorder (ASD) is currently estimated to be 1 in 36 children. While much is known about the impact of ASD on family and community functioning as well as treatment outcomes, less is known about a relatively new categorization of ASD, called "profound autism." The current study evaluated 14 consecutively admitted patients meeting criteria for profound autism to a specialized psychiatric inpatient and partial hospitalization program. We then selected 15 non-profoundly autistic youth admitted immediately before or after each profoundly autistic youth to serve as a comparison. Patient caregivers completed measures about parental stress and the severity and frequency of patient problem behavior, and patients participated in functional analyses of problem behavior and function-based treatment programs during their admission. Results showed profoundly autistic youth spent an average of 14 more days admitted to the psychiatric unit, and they engaged in higher parent-reported severity and frequency of self-injurious and stereotypic behavior. Functional analysis results for profoundly autistic youth showed a higher occurrence of automatically reinforced problem behavior but otherwise similar results. As well, profoundly autistic youth showed a lower percentage reduction in problem behavior at the end of the psychiatric hospitalization than their non-profoundly autistic peers. Profoundly autistic youth seem to require a high level of behavioral support, even after psychiatric hospitalization. Insurance companies and therapists need to recognize these challenges and invest sufficient resources to meet their treatment needs.

Expression of key molecules of the classical inflammation activation pathway in blood leukocytes of autistic children

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders, whose causes are currently not fully understood. Research suggests that inflammation and changes in immune functions may play an important role in the development of autism. Increased levels of proinflammatory cytokines in the brains of autistic children lead to negative regulation of synaptic plasticity, as well as impaired proliferation and differentiation of neurons through activation of the nuclear factor kappa B (NF-κB) signaling pathway. The purpose of the work is to analyze the levels of mRNA: TLR2, TLR4, MyD88, IκBα, NF-κB p50, NF-κB p65 in peripheral blood leukocytes of children in comparison with the severity of autism spectrum disorders. The study included 126 children aged from 3 to 13 years (the ratio of boys to girls was 4:1): 45 children with typical neurodevelopment, and 81 children with a clinically confirmed diagnosis of autism. According to the Childhood Autism Rating Scale, 51 children had mild to moderate ASD (CARS score: 29-36), and 30 children had severe autism (CARS score: 36-60). The expression of inflammatory signal transduction pathway molecules was determined in peripheral blood leukocytes using real-time polymerase chain reaction with SYBRGreen. To compare the samples, one-way ANOVA and Tukey’s test were used. It was found that in leukocytes of children with severe ASD, the expression of the adapter protein MyD88 and the p65 subunit of the nuclear transcription factor NF-κB was significantly reduced, and the expression of the NF-κB inhibitor, IκBα, was significantly increased, compared to the control group. In leukocytes of children with mild ASD, a decrease in NF-κB p65 expression was found at a trend level. When comparing groups of children with different severity of autism symptoms (mild/severe), no significant differences were found in the levels of mRNA of key signaling molecules of the classical inflammation activation pathway in blood leukocytes. Thus, in the blood leukocytes of children with severe ASD, suppression of the expression of key molecules of the classical inflammation activation pathway (NF-κB) is observed, which leads to a decrease in the expression of pro-inflammatory cytokines: IL-1β, IL-18 and IL-2, against the background of increased expression of key cytokine of Th1 cells – IFNγ.

Stratification of Gut Microbiota Profiling Based on Autism Neuropsychological Assessments

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

Validation of the Sinhala version of the Autism Treatment Evaluation Checklist (ATEC)

Background: Autism Spectrum Disorder is a neuro developmental disorder which has a trend in its increasing prevalence globally. Measuring the outcome of intervention will have a great value for parents and clinicians. At present, there are no tools validated in the Sri Lankan setting to assess treatment outcomes in Autism Spectrum Disorder. Autism Treatment Evaluation Checklist (ATEC) is a self-administered questionnaire in Sinhala for parents/caregivers that is a feasible method of evaluating outcome in a busy clinic.Aims: This study was conducted to translate and culturally adapt the ATEC to the Sinhala language and to establish the validity and reliability of the translation to the local setting.Methods: Permission was sought from the developers of the ATEC questionnaire and ethical approval was obtained for the study. Study was conducted in two stages. In the first stage, ATEC was translated using the translation-back translation method. An expert panel produced a pre-final questionnaire which was pre-tested prior to formulating the final Sinhala version of ATEC. The second stage of the study was conducted to establish validity and reliability of Sinhala ATEC questionnaire in the Sri Lankan popu-lation. Content validity was assured in each step of the translation by the expert committee. Construct validity of the Sinhala ATEC questionnaire was assessed by comparing the sample of 119 parent/caregiver filled final version of the Sinhala ATEC score against the Consultant Child and Adolescent Psychiatrist assessment of the same children conducted independently and recorded according to DSM-5 (level 1, 2 or 3). Test-retest reliability was determined by the same parent/caregiver filling the Sinhala ATEC one week later, in a sample of 14 children. Intra-rater reliability was taken by com-paring 18 pairs of parents/caregivers Sinhala ATEC scores for the same child.Results: Sinhala ATEC showed high validity and reliability. Its concurrent validity has a strong positive Pearson correlation of 0.856 with the Consultant Psychiatrist assessment. Correlation was higher in total score and as well as in subscale II- Sociability score of the Sinhala ATEC. Internal consistency was revealed by Cronbach’s alpha 0.778. Cut off points to distinguish mild autism spectrum disorder from the rest taken as “48 or less” with sensitivity 82%, specificity 94% and area under the curve 0.968. Cut off to separate severe autism spectrum disorder from the rest were taken as “76 or more” with sensitivity 84%, specificity 90%and area under the curve 0.971. Reliability tests, intra class correlation was 0.98 and 0.96 for test-retest and intra rater reliability showed high reliability of Sinhala ATEC. For developing burnout in this study population.Conclusions: Translated version of Sinhala ATEC is suitable for the use in the Sri Lankan population as it shows high validity and reliability. However, further studies are recommended in other areas of the country to assess its usefulness across diverse subcultures and clinical settings.

Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism

BackgroundWhole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex.MethodsTo address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family.ResultsWe observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females.ConclusionsOur findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism’s genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Beyond the Spectrum: Subtype-Specific Molecular Insights into Autism Spectrum Disorder Via Multimodal Data Integration.

Some toddlers with autism spectrum disorder (ASD) have mild social symptoms and developmental improvement in skills, but for others, symptoms and abilities are moderately or even severely affected. Those with profound autism have the most severe social, language, and cognitive symptoms and are at the greatest risk of having a poor developmental outcome. The little that is known about the underlying biology of this important profound autism subtype, points clearly to embryonic dysregulation of proliferation, differentiation and neurogenesis. Because it is essential to gain foundational knowledge of the molecular biology associated with profound, moderate, and mild autism clinical subtypes, we used well-validated, data-driven patient subtyping methods to integrate clinical and molecular data at 1 to 3 years of age in a cohort of 363 ASD and controls representative of the general pediatric population in San Diego County. Clinical data were diagnostic, language, cognitive and adaptive ability scores. Molecular measures were 50 MSigDB Hallmark gene pathway activity scores derived from RNAseq gene expression. Subtyping identified four ASD, typical and mixed diagnostic clusters. 93% of subjects in one cluster were profound autism and 93% in a different cluster were control toddlers; a third cluster was 76% moderate ability ASD; and the last cluster was a mix of mild ASD and control toddlers. Among the four clusters, the profound autism subtype had the most severe social symptoms, language, cognitive, adaptive, social attention eye tracking, social fMRI activation, and age-related decline in abilities, while mild autism toddlers mixed within typical and delayed clusters had mild social symptoms, and neurotypical language, cognitive and adaptive scores that improved with age compared with profound and moderate autism toddlers in other clusters. In profound autism, 7 subtype-specific dysregulated gene pathways were found; they control embryonic proliferation, differentiation, neurogenesis, and DNA repair. To find subtype-common dysregulated pathways, we compared all ASD vs TD and found 17 ASD subtype-common dysregulated pathways. These common pathways showed a severity gradient with the greatest dysregulation in profound and least in mild. Collectively, results raise the new hypothesis that the continuum of ASD heterogeneity is moderated by subtype-common pathways and the distinctive nature of profound autism is driven by the differentially added profound subtype-specific embryonic pathways.

Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations

A major driver of neuronal hyperexcitability is dysfunction of K+ channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders. However, the impact of these variants on the molecular mechanisms underlying KCNQ3 channel function remains poorly understood and existing treatments have significant side effects. Here, we use voltage clamp fluorometry, molecular dynamic simulations, and electrophysiology to investigate NDD-associated variants in KCNQ3 channels. We identified two distinctive mechanisms by which loss– and gain–of function NDD-associated mutations in KCNQ3 affect channel gating: one directly affects S4 movement while the other changes S4-to-pore coupling. MD simulations and electrophysiology revealed that polyunsaturated fatty acids (PUFAs) primarily target the voltage-sensing domain in its activated conformation and form a weaker interaction with the channel’s pore. Consistently, two such compounds yielded partial and complete functional restoration in R227Q- and R236C-containing channels, respectively. Our results reveal the potential of PUFAs to be developed into therapies for diverse KCNQ3-based channelopathies.

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism with and without Profound Impairment: An Observational Study.

Catatonia is a highly morbid psychomotor and affective disorder which can affect autistic individuals with and without profound impairment. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments 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 1st, 2021 to May 31st, 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 patients were identified with 39 (86.7%) meeting criteria for profound autism. All patients received pharmacotherapy. 44 (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. Fourteen patients (31.1%) attempted to taper off benzodiazepines 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 symptomatic 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.

Oral health status and dental treatment needs in children with autism spectrum disorder

ObjectiveTo evaluate oral health care practices, health status, and dental treatment needs in children with Autism Spectrum Disorder (ASD). MethodsThis cross-sectional study included 96 children diagnosed with ASD per the DSM-V criteria and 96 typically developing healthy children. The WHO form assessed oral health status and dental treatment needs. ResultsOver 50 % of ASD children had mild/moderate autism, 35.4 % had severe autism, and 13.5 % had autistic traits. ASD children experienced more toothbrushing difficulties compared to non-ASD children. Based on Nyvad's criteria and decayed/filled teeth (dft) index, non-ASD children had higher caries prevalence than ASD children, indicating less need for restorative treatments in the ASD group. However, ASD children had poorer plaque scores than non-ASD children. A significantly higher percentage of ASD children exhibited harmful oral behaviors, including mouth breathing, lip biting, bruxism, nail biting, object biting, and self-injury (p < 0.001). ASD children also showed increased traumatic dental injuries compared to non-ASD children. ConclusionCompared to non-ASD peers, children with ASD have lower dental caries prevalence and less need for restorations, yet poorer plaque control. They also demonstrate more frequent oral self-injuries. ASD status appears related to toothbrushing difficulties. These findings highlight the need for tailored oral health interventions for children with ASD.

Changing smiles and minds-a community-based trial on parental knowledge impact on early childhood caries.

This study was carried out in New York City over a period of twelve months for each child. 1207 children from 977 families, with clinically diagnosed ECC, were recruited. Inclusion criteria included children that had at least one filled or decayed primary tooth surface and were aged between 2 years to 6 years. Exclusion criteria included children that may have conditions that would have prevented the provision of oral hygiene habits or moderation of diet, for example children with severe autism. Families were recruited from local specialist residency programmes within the city or by direct referral from local CHWs. Evaluation of the parental education was established through use of electronic surveys at baseline level and follow up following CHWs' intervention. The data was collected between 2015 and 2017 and required follow up appointments that were completed via telephone and other remote methods. Data collection separated caries risk factors into six domains with 26 factions across the pre- and post-intervention period. These addressed both parental knowledge of the aetiology of caries and factors that can contribute to this. Domains included titles such as saliva factors, hygiene, diet, severity/susceptibility, and outcome expectations. Parents were asked to note their agreement with the statements using a four-point scale (Strongly Agree, Agree, Disagree and Strongly Disagree). The survey was made up of statements including themes of caries risk factors, and behavioural science that can contribute to caries development. Examples include 'drinking juice can cause tooth decay' and 'all kids get tooth decay'. Correct answers would be given as part of the targeted advice and education given by the CHWs at subsequent visits. Data was collected from a total of 669 parents of 977 taking part in the study. Analysis focussed on the trend of changing knowledge of parents from baseline to follow up. The analysis also assessed features of the participants including the parents' first language, education level, country of birth, average age of the children and their insurance status - this was then assessed to see if this influenced the parents' beliefs and associations. Results found there was an improvement in the parental knowledge of salivary risks for caries, hygiene input and dietary effect post intervention. The only differing result was the statement that 'tooth decay is very common' - this showed a reduced change. The study concluded that the MySmileBuddy programme did improve parental education on Early Childhood Caries and factors influencing the risk of this, though acknowledges that there should be further exploration in the clinical impact that this education would have on the patients' caries status from the CHW input.

Self-Injurios Behaviour in an Adult with Autism Spectrum Desorder

Self-injurious conduct is a highly maladaptive behaviour that is often associated with severe mental retardation and autism. Research has highlighted the complexity and multifactorial nature of the aetiology of the disorder. In this paper we present, after careful analysis, the treatment of an adult subject with autism spectrum disorder to reduce self-injurious behaviour and teach him more effective and less disabling ‘coping strategies’. The experimental design used is of the criterion-variant type. The analysis of the data showed that the goals set were achieved. In the post-treatment sessions, we achieved extinction of the target behaviour.

A Comparison of Parent-Reported Severe Autism With Mild/Moderate Autism Among US Children.

An expert commission has proposed the term "profound" autism for children on the spectrum who are minimally verbal or nonverbal and have intellectual disability (ID), behavioral challenges, and co-occurring conditions. It is unknown whether parents' rating of "severe" autism aligns with the definition of "profound" autism. Using the National Survey of Children's Health, we sought to (1) estimate the prevalence of parent-reported severe autism, (2) identify child characteristics that are associated with severe autism, (3) compare health care utilization, and (4) compare caregiver stress and resilience between families of children with severe versus mild/moderate autism. Parent responses on the 2018 to 2019 NSCH were used to compare school-age children with parent-reported severe autism and those with mild/moderate autism. Descriptive statistics, χ 2 tests, and logistic regression were used for statistical analysis. Among parents of 1,368 US children with autism, 10.1% characterized their child's autism as severe, a prevalence of 1 in 333. Parents of children with severe autism were more likely to report ID (45% vs 12.1%, p < 0.001), language delay (88% vs 58.7%, p < 0.001), and difficulties in dressing and bathing (67% vs 19.2%, p < 0.001). Children with severe autism had more behavioral problems and co-occurring conditions but were no more likely to see specialists or receive autism-specific behavioral therapy. Their caregivers reported more stress and less resilience. The characteristics of "profound" autism and parent-reported "severe" autism significantly overlap, allowing the use of the NSCH for studies of this vulnerable population. Children with profound/severe autism could benefit from more behavioral therapy, specialty care, and family support.

Autism Severity, Adverse Childhood Experiences, and Oral Health: A Comparative Study of Adolescents in the United States.

Dental health significantly influences overall child physical well-being, academic success, and psychosocial development. This paper explores the intersection of a range of Autism Spectrum Disorder (ASD) functionality, multiple types of Adverse Childhood Experiences (ACEs), and dental health in adolescents. The purpose is to investigate the independent and interactive effects of ASD severity and ACEs on dental outcomes. Data from the 2018 and 2019 National Surveys of Children's Health were analyzed, focusing on 28,263 adolescents (ages 11-17). Logistic regressions assessed associations between ASD severity (mild, moderate, severe), cumulative number of ACEs, and dental outcomes (teeth condition, cavities or bleeding gums, check-ups, cleanings). Covariates included demographic and socioeconomic factors. Controlling for covariates, severe autism independently increased the odds of poor teeth (odds ratio = 6.17), cavities or bleeding gums (OR = 3.76), no previous year check-up(OR = 2.94), and no previous year cleaning (OR = 4.20). Higher ACE scores also independently increased the odds of all dental outcomes. Interactions revealed a cumulative effect of multiple ACEs on poor dental outcomes only for adolescents with severe levels of autism. This study illuminates the heightened vulnerability of adolescents with severe autism and a history of ACEs, emphasizing the need for targeted interventions. Multidisciplinary strategies integrating dental care and mental health support within tailored interventions are crucial for improving dental health and access for older youth with low functioning autism. While these findings provide valuable insights, the cross-sectional design and reliance on parental reports necessitate cautious interpretation.

Effect of Infra Low Frequency (ILF) neurofeedback training on EEG in children with autism spectrum disorders.

To investigate whether Infra-low frequency Neurofeedback (ILF-NFB) training can improve brain electrical activity in children with autism spectrum disorders ASD. This single arm pre and post intervention study was carried out at IBMS (Institute of Basic Medical Sciences), Khyber Medical University, Peshawar and Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad from January 2021 to December 2022. A purposive sampling technique was used. Thirty-five ASD children (male=24; female=11; 7-17 years) were provided with 30 sessions of infra low frequency (ILF) neurofeedback training for 15-20 minutes, during 10 weeks. Childhood Autism Rating Scale (CARS) scoring was done and electroencephalogram (EEG) activity was compared before and after ILF-NF training sessions. Around 62.9% participants had mild-moderate autism and 37.1% had severe autism. Wilcoxon Signed rank test revealed a significant decline in delta (Pre-test=47.31±19.22, Post-test=22.07±6.83; p=<0.001), theta (Pre-test=24.75±16.62, Post-test=12.37±3.59; p=<0.001) and alpha (Pre-test=12.01±9.81, Post-test=4.03±1.61; p=< 0.001) waves. Mann Whitney U test exhibited no significant gender differences in EEG pattern before and after neurofeedback except in theta waves (p=0.03) before the intervention. Decline in delta, theta, beta and alpha waves propose that ILF-NF training can be effective in improving the EEG activity. ILF-NFB can be perceived as a valuable non-invasive, non-pharmacological intervention for improving EEG pattern via reintegration of brain activity resulting in increased the attention and focus, enhanced mental stability and cognitive engagement.

Toward a functional classification for autism in adulthood.

Autism spectrum disorder (ASD) is a heterogeneous condition that affects development and functioning from infancy through adulthood. Efforts to parse the heterogeneity of the autism spectrum through subgroups such as Asperger's and Profound Autism have been controversial, and have consistently struggled with issues of reliability, validity, and interpretability. Nonetheless, methods for successfully identifying clinically meaningful subgroups within autism are needed to ensure that research, interventions, and services address the range of needs experienced by autistic individuals. The purpose of this study was to generate and test whether a simple set of questions, organized in a flowchart, could be used in clinical practice and research to differentiate meaningful subgroups based on individuals' level of functioning. Once generated, subgroups could also be compared to the recently proposed administrative category of Profound Autism and to groupings based on standardized adaptive measures. Ninety-seven adults with autism or related neurodevelopmental disorders participating in a longstanding longitudinal study, or their caregivers if they could not answer for themselves, completed phone interviews when the participants were ~30 years old. Information from these phone interviews was used to generate vignettes summarizing characteristics and aspects of the daily lives of each participant (e.g., language level, vocational activities, and social relationships). Three expert clinicians then used these vignettes to classify each participant based on their level of support needs. Meaningfully distinct subgroups within the sample were identified which could be reliably distinguished from one another. Implications of such categorizations and future directions are discussed.

"There is No Help:" Caregiver Perspectives on Service Needs for Adolescents and Adults with Profound Autism.

The underrepresentation of individuals with profound autism (who require 24/7 access to care) in autism research has resulted in limited knowledge about their service needs and a lack of evidence-based practices tailored to those needs. This study explored caregiver perspectives on service needs, barriers to accessing care, and treatment priorities to guide treatment development and improvement of service delivery. A sequential mixed-methods design integrated quantitative survey data (n = 423; Mage = 18.89years; 26.7% female) with qualitative interviews (n = 20) with caregivers of adolescents and adults with profound autism. Quantitative findings indicated regular socialization opportunities were the most frequently endorsed unmet service need (60.3% of caregivers), followed by primary health care with autism-trained staff (59.3%), social skills instruction (55.8%), life skills instruction (51.3%), and behavioral support (47.3%). Higher likelihood of needing social activity groups was associated with elevated emotional reactivity, higher language level, minoritized ethnicity, and lower household income. Greater need for specialized primary health care was associated with lower income, while the need for social and life skills instruction was associated with increased age and elevated dysphoria. Qualitative analysis identified 10 themes that converged and expanded quantitative findings by highlighting a pervasive shortage of individualized, goal-oriented services, common barriers to care, and the priority of developing centralized treatment settings that coordinate care throughout adulthood. This study identified pressing service needs for adolescents and adults with profound autism in the United States. These insights are crucial for improving the accessibility and quality of clinical care.

Transanal proximal rectosigmoidectomy: a single-center experience in surgically treated severe medically refractory idiopathic constipation.

To present the functional results after a transanal proximal rectosigmoidectomy in patients with severe idiopathic constipation in which medical treatment has failed. Patients with severe idiopathic constipation who underwent transanal proximal rectosigmoidectomy (TPRS) at Children's Hospital Colorado between June 2019 and March 2024 were included in the study. We compared multiple pre- and post-operative outcome measures and the patient's bowel regimen before and after resection. Fourteen patients underwent TPRS, 10 of whom were male. The average age at the time of surgery was 10.1years (range 5-19). Seven patients have moderate to severe autism. Constipation-related clinic visits, family calls, procedural intervention, emergency room visits, and hospitalizations notably decreased frequency after TPRS. Laxative dosages and enema volume requirements were also reduced after surgery. Before surgery, all the patients suffered from daily fecal accidents, while post-operatively, all were completely free of stool accidents. In our experience, for patients who suffer from severe medically refractory idiopathic constipation, TPRS has provided improvement in their symptoms and decreased the complications inherent to this chronic disease. Parents and patients attest to a profound positive transformation in their quality of life after surgery.

The Role of Adverse Childhood Experience in the Relationship Between Autism Severity and Early Intervention and Special Education Plan.

The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the impact of adverse childhood experiences (ACEs) on this association. This study used the 2020-2021 National Survey of Children's Health (NSCH) and included 2,537 children aged 3-17 years old who currently have ASD. Multivariable logistic regression, controlling for demographic and family characteristics and health status, was used to explore the association between autism severity and having an early intervention plan. The analysis was stratified by the number of ACEs to explore their role in the association. Children with moderate or severe ASD were more likely to have a special education or early intervention plan than those with mild ASD in the crude and adjusted models. This association continued to be true for children who experienced 1 ACE (aOR: 2.28, 95%CI: 1.09-4.77) but not true for those who experienced no ACEs (aOR: 1.16, 95%CI: 0.70-1.94) and 2 or more ACEs (aOR: 1.84, 95%CI: 0.92-3.69). Results demonstrate that children with moderate or severe autism were more likely to receive early intervention or special education. This association changed depending on the number of ACEs experiences.

Corrigendum: Understanding profound autism: implications for stigma and supports

Corrigendum: Understanding profound autism: implications for stigma and supports

Carvedilol increases seizure resistance in a mouse model of SCN8A-derived epilepsy.

Patients with mutations that alter the function of the sodium channel SCN8A present with a range of clinical features, including mild to severe seizures, developmental delay, intellectual disability, autism, feeding dysfunction, motor impairment, and hypotonia. In an effort to identify compounds that could be potentially beneficial in SCN8A-associated epilepsy, Atkin et al. conducted an in vitro screen which resulted in the identification of 90 compounds that effectively reduced sodium influx into the cells expressing the human SCN8A R1872Q mutation. The top compounds that emerged from this screen included amitriptyline, carvedilol, and nilvadipine. In the current study, we evaluated the ability of these three compounds to increase resistance to 6Hz or pentylenetetrazole (PTZ)-induced seizures in wild-type CF1 mice and in a mouse line expressing the human SCN8A R1620L mutation. We also evaluated the effects of fenfluramine administration, which was recently associated with a 60%-90% decrease in seizure frequency in three patients with SCN8A-associated epilepsy. While amitriptyline, carvedilol, and fenfluramine provided robust protection against induced seizures in CF1 mice, only carvedilol was able to significantly increase resistance to 6Hz- and PTZ-induced seizures in RL/+ mutants. These results provide support for further evaluation of carvedilol as a potential treatment for patients with SCN8A mutations.