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

OBJECTIVE: 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. METHODS: 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, χ2 tests, and logistic regression were used for statistical analysis. RESULTS: 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. CONCLUSION: 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.

A culturally grounded autism parent training program with Black parents.

LAY ABSTRACT: Parent training programs have been well-studied in Autism Spectrum Disorders and shown to increase a parent's feeling of empowerment, advocacy skills, and treatment enrollment for their child. The majority of parent training interventions have been developed without considering the unique needs of under-represented communities, such as the Black community. Black children with autism are not only misdiagnosed or not diagnosed at all, but are not accessing services equally compared to their White peers. There is an urgent need for culturally adapted interventions in order to decrease the disparity gap. The Color of Autism Foundation developed and ran a parent training program for Black parents of children with autism. The program was grounded in two key features: (1) creating a circle of support for parents to connect and heal from ongoing and historical racial trauma and (2) using parents of Black children with autism as the main facilitators. We believe this increased parent's ability to engage in the educational aspects of the training. Overall, parents reported high levels of satisfaction with the training were highly engaged (attended an average of five of six sessions) and reported high levels of empowerment. Parents also reported continued mistrust in the medical and research community and a need for more Black providers. Further work should examine the relationship of the parent and provider in autism treatment and study the impact of circles of healing for Black families.

Sex differences in age of diagnosis of autism spectrum disorder: Preliminary evidence from Uganda.

This study was performed to determine (a) the age at which autism spectrum disorder (ASD) is first diagnosed in Ugandan children receiving mental health services, (b) whether age at diagnosis varies by sex and clinical presentation, and (c) the average age of ASD diagnosis in children manifesting comorbid conditions. A retrospective chart review was performed and demographic as well as clinical data were collected from children with ASD diagnoses who attended two mental health clinics in Uganda between 2014 and 2019. Descriptive statistics such as percentages, means, and standard deviations were used to summarize the data. Independent t-test was also performed to determine differences in the mean age of diagnosis between males and females. Two hundred and thirty-seven (156 males, 81 females) children with ASD were identified. The average age of ASD diagnosis was (6.9 ± 4.0) years. A statistically significant difference in age of ASD diagnosis was found between males and females (t = -2.106, p = 0.036), such that on average females received a diagnosis at least 1 year later than males. Of the 237 participants, 53.6% were identified with ASD only, 16.0% had ASD and ADHD, 10.5% were diagnosed with ASD and epilepsy, and 7.2% had a diagnosis of complex ASD. The results confirm delays in access to ASD diagnosis and suggest that females are more likely to receive a ASD diagnosis later than males within the Ugandan context. ASD awareness should be intensified to improve public or professional knowledge about ASD to enhance early identification in Uganda.

Caregivers' estimate of early childhood developmental status in rural Uganda: a cross-sectional study.

OBJECTIVE: To characterise developmental milestones among young children living in rural communities in Uganda. DESIGN: Cross-sectional study. SETTING: Iganga-Mayuge Health and Demographic Surveillance Site in rural eastern Uganda. PARTICIPANTS: A total of 720 caregivers of children aged 3-4 years old from a health and demographic surveillance site in rural eastern Uganda were recruited into this study. Caregivers reported on their child's developmental skills and behaviours using the 10-item Early Childhood Development Index (ECDI) developed by UNICEF. Childhood development was characterised based on the ECDI's four domains: literacy-numeracy, learning/cognition, physical and socioemotional development. As an exploratory analysis, we implemented a hierarchical agglomerative cluster analysis to identify homogenous subgroups of children based on the features assessed. The cluster analysis was performed to identify potential subgroups of children who may be at risk of developmental problems. RESULTS: Between November 2017 and June 2018, 720 caregivers of children aged 3-4 years completed the ECDI. The proportions of children at risk of delay in each domain were as follows: literacy-numeracy: 75% (n=538); socioemotional development: 22% (n=157); physical: 3% (n=22); and cognitive: 4% (n=32). The cluster analysis revealed a three-cluster solution that included 93% of children assigned to a low-risk group, 4% assigned to a moderate-risk group and 3% assigned to a high-risk group characterised by low scores in almost all domains. CONCLUSION: The findings suggest that a high proportion of children in rural eastern Uganda demonstrate poor literacy-numeracy skills. These results underscore the need to improve population-based screening and intervention efforts to improve early childhood developmental outcomes, particularly in literacy and socioemotional domains, in low-income and middle-income countries such as Uganda.

Cognitive Development One Year After Infantile Critical Pertussis.

OBJECTIVES: Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with critical pertussis 1 year after PICU discharge. DESIGN: Prospective cohort study. SETTING: Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States. PATIENTS: Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours. INTERVENTIONS: The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview. MEASUREMENTS AND MAIN RESULTS: Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p < 0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p < 0.003) and Hispanic ethnicity (p < 0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not. CONCLUSIONS: Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.

Prevalence of Autism Spectrum Disorders in Guanajuato, Mexico: The Leon survey.

There are no epidemiological data on autism for Mexico. This study was conducted to generate a first estimate of ASD prevalence in Mexico. We surveyed children age eight in Leon (Guanajuato). The sample was stratified in two strata: (1) children having special education and medical records (SEMR; N = 432) and (2) children attending regular schools (GSS; N = 11,684). GSS children were screened with the SRS and those with the highest scores were invited to a diagnostic evaluation. The final sample comprised 36 children (80.6 % male) who had confirmed ASD. A third had intellectual disability, 25 % were non-verbal, 69 % had co-occurring behavioral problems. The prevalence overall was 0.87 % (95 % CI 0.62, 1.1 %). This survey provides an estimate for ASD prevalence in Mexico that is consistent with recent studies.

Identifying autism in a brief observation.

BACKGROUND: Pediatricians, neurologists, and geneticists are important sources for autism surveillance, screening, and referrals, but practical time constraints limit the clinical utility of behavioral observations. We analyzed behaviors under favorable conditions (ie, video of autism evaluations reviewed by experts) to determine what is optimally observable within 10-minute samples, asked for referral impressions, and compared these to formal screening and developmental testing results. METHODS: Participants (n = 42, aged 15 to 33 months) were typically developing controls and children who screened positive during universal autism screening within a large community pediatric practice. Diagnostic evaluations were performed after screening to determine group status (autism, language delay, or typical). Licensed psychologists with toddler and autism expertise, unaware of diagnostic status, analyzed two 10-minute video samples of participants' autism evaluations, measuring 5 behaviors: Responding, Initiating, Vocalizing, Play, and Response to Name. Raters were asked for autism referral impressions based solely on individual 10-minute observations. RESULTS: Children who had autism showed more typical behavior (89% of the time) than atypical behavior (11%) overall. Expert raters missed 39% of cases in the autism group as needing autism referrals based on brief but highly focused observations. Significant differences in cognitive and adaptive development existed among groups, with receptive language skills differentiating the 3 groups. CONCLUSIONS: Brief clinical observations may not provide enough information about atypical behaviors to reliably detect autism risk. High prevalence of typical behaviors in brief samples may distort clinical impressions of atypical behaviors. Formal screening tools and general developmental testing provide critical data for accurate referrals.

Atypical laterality of resting gamma oscillations in autism spectrum disorders.

Abnormal brain oscillatory activity has been found in autism spectrum disorders (ASD) and proposed as a potential biomarker. While several studies have investigated gamma oscillations in ASD, none have examined resting gamma power across multiple brain regions. This study investigated resting gamma power using EEG in 15 boys with ASD and 18 age and intelligence quotient matched typically developing controls. We found a decrease in resting gamma power at right lateral electrodes in ASD. We further explored associations between gamma and ASD severity as measured by the Social Responsiveness Scale (SRS) and found a negative correlation between SRS and gamma power. We believe that our findings give further support of gamma oscillations as a potential biomarker for ASD.

The each child study: systematic screening for autism spectrum disorders in a pediatric setting.

OBJECTIVE: The goal of this study was to investigate the feasibility and outcome of a systematic autism screening process for all toddlers (aged 14-30 months) in a large, community-based pediatric practice. METHODS: All toddlers who presented to the clinic during the 6-month screening period were eligible. We used 2 screening questionnaires and allowed physicians to refer directly to capture as many children as possible. Receptionists and medical assistants distributed and collected screening questionnaires; research staff did all scoring and follow-up, either by telephone or in person when indicated. RESULTS: We obtained a high rate of screening (80% of eligible children). Of the 796 children screened, 3 had already been diagnosed with an autism spectrum disorder (ASD); an additional 10 children who showed signs of early ASD that warranted further evaluation or intervention were identified. Formal screening measures identified more children with ASD than did clinical judgment or caregiver concerns; however, no single method (ie, questionnaire, caregiver concerns, provider concerns) identified all children with signs of early ASD. We had excellent participation from racially and ethnically diverse families, including Spanish-speaking families. Thirty-two percent of the children who were screened did not present for a well-child visit during the study period and were screened at a sick visit, follow-up visit, or injection appointment. CONCLUSIONS: A partnership between pediatricians and autism specialists resulted in effective, systematic autism screening. Future studies should examine how to create effective systems of care.

Genome-wide linkage analyses of two repetitive behavior phenotypes in Utah pedigrees with autism spectrum disorders.

BACKGROUND: It has been suggested that efforts to identify genetic risk markers of autism spectrum disorder (ASD) would benefit from the analysis of more narrowly defined ASD phenotypes. Previous research indicates that 'insistence on sameness' (IS) and 'repetitive sensory-motor actions' (RSMA) are two factors within the ASD 'repetitive and stereotyped behavior' domain. The primary aim of this study was to identify genetic risk markers of both factors to allow comparison of those markers with one another and with markers found in the same set of pedigrees using ASD diagnosis as the phenotype. Thus, we empirically addresses the possibilities that more narrowly defined phenotypes improve linkage analysis signals and that different narrowly defined phenotypes are associated with different loci. Secondary aims were to examine the correlates of IS and RSMA and to assess the heritability of both scales. METHODS: A genome-wide linkage analysis was conducted with a sample of 70 multiplex ASD pedigrees using IS and RSMA as phenotypes. Genotyping services were provided by the Center for Inherited Disease Research using the 6 K single nucleotide polymorphism linkage panel. Analysis was done using the multipoint linkage software program MCLINK, a Markov chain Monte Carlo (MCMC) method that allows for multilocus linkage analysis on large extended pedigrees. RESULTS: Genome-wide significance was observed for IS at 2q37.1-q37.3 (dominant model heterogeneity lod score (hlod) 3.42) and for RSMA at 15q13.1-q14 (recessive model hlod 3.93). We found some linkage signals that overlapped and others that were not observed in our previous linkage analysis of the ASD phenotype in the same pedigrees, and regions varied in the range of phenotypes with which they were linked. A new finding with respect to IS was that it is positively associated with IQ if the IS-RSMA correlation is statistically controlled. CONCLUSIONS: The finding that IS and RSMA are linked to different regions that only partially overlap regions previously identified with ASD as the phenotype supports the value of including multiple, narrowly defined phenotypes in ASD genetic research. Further, we replicated previous reports indicating that RSMA is more strongly associated than IS with measures of ASD severity.

Genome-wide linkage using the Social Responsiveness Scale in Utah autism pedigrees.

BACKGROUND: Autism Spectrum Disorders (ASD) are phenotypically heterogeneous, characterized by impairments in the development of communication and social behaviour and the presence of repetitive behaviour and restricted interests. Dissecting the genetic complexity of ASD may require phenotypic data reflecting more detail than is offered by a categorical clinical diagnosis. Such data are available from the Social Responsiveness Scale (SRS) which is a continuous, quantitative measure of social ability giving scores that range from significant impairment to above average ability. METHODS: We present genome-wide results for 64 multiplex and extended families ranging from two to nine generations. SRS scores were available from 518 genotyped pedigree subjects, including affected and unaffected relatives. Genotypes from the Illumina 6 k single nucleotide polymorphism panel were provided by the Center for Inherited Disease Research. Quantitative and qualitative analyses were done using MCLINK, a software package that uses Markov chain Monte Carlo (MCMC) methods to perform multilocus linkage analysis on large extended pedigrees. RESULTS: When analysed as a qualitative trait, linkage occurred in the same locations as in our previous affected-only genome scan of these families, with findings on chromosomes 7q31.1-q32.3 [heterogeneity logarithm of the odds (HLOD) = 2.91], 15q13.3 (HLOD = 3.64), and 13q12.3 (HLOD = 2.23). Additional positive qualitative results were seen on chromosomes 6 and 10 in regions that may be of interest for other neuropsychiatric disorders. When analysed as a quantitative trait, results replicated a peak found in an independent sample using quantitative SRS scores on chromosome 11p15.1-p15.4 (HLOD = 2.77). Additional positive quantitative results were seen on chromosomes 7, 9, and 19. CONCLUSIONS: The SRS linkage peaks reported here substantially overlap with peaks found in our previous affected-only genome scan of clinical diagnosis. In addition, we replicated a previous SRS peak in an independent sample. These results suggest the SRS is a robust and useful phenotype measure for genetic linkage studies of ASD. Finally, analyses of SRS scores revealed linkage peaks overlapping with evidence from other studies of neuropsychiatric diseases. The information available from the SRS itself may, therefore, reveal locations for autism susceptibility genes that would not otherwise be detected.

Partially enhanced thalamocortical functional connectivity in autism.

Based on evidence for thalamic abnormalities in autism, impairments of thalamocortical pathways have been suspected. We examined the functional connectivity between thalamus and cerebral cortex in terms of blood oxygen level dependent (BOLD) signal cross-correlation in 8 male participants with high-functioning autism and matched normal controls, using functional MRI during simple visuomotor coordination. Both groups exhibited widespread connectivity, consistent with known extensive thalamocortical connectivity. In a direct group comparison, overall more extensive connectivity was observed in the autism group, especially in the left insula and in right postcentral and middle frontal regions. Our findings are inconsistent with the hypothesis of general underconnectivity in autism and instead suggest that subcortico-cortical connectivity may be hyperfunctional, potentially compensating for reduced cortico-cortical connectivity.

Activity and functional connectivity of inferior frontal cortex associated with response conflict.

The traditional Stroop test of cognitive interference requires overt speech responses. One alternative, the counting Stroop, generates cognitive interference similar to the traditional Stroop test but allows button press responses. Previous counting Stroop studies have used concrete words in the control condition, which may have masked inferior frontal activation. We studied 7 healthy young adults using fMRI on a counting Stroop condition, with a nonlinguistic control condition (geometric shapes). As expected, we found activation in bilateral inferior frontal gyri, as well as in lateral and medial prefrontal, inferior parietal, and extrastriate cortices. Additional functional connectivity analyses using inferior frontal activation clusters (right area 44, left area 47) as seed volumes showed connectivity with superior frontal area 8 and anterior cingulate gyrus, suggesting that the role of inferior frontal cortex was related to response conflict and inhibition. Connectivity with left perisylvian language areas was not observed, which further underscores the nonlinguistic nature of inferior frontal activity. We conclude that bilateral inferior frontal cortex is involved in response suppression associated with interference in the counting Stroop task.

Reduced functional connectivity between V1 and inferior frontal cortex associated with visuomotor performance in autism.

Some recent evidence has suggested abnormalities of the dorsal stream and possibly the mirror neuron system in autism, which may be responsible for impairments of joint attention, imitation, and secondarily for language delays. The current study investigates functional connectivity along the dorsal stream in autism, examining interregional blood oxygenation level dependent (BOLD) signal cross-correlation during visuomotor coordination. Eight high-functioning autistic men and eight handedness and age-matched controls were included. Visually prompted button presses were performed with the preferred hand. For each subject, functional connectivity was computed in terms of BOLD signal correlation with the mean time series in bilateral visual area 17. Our hypothesis of reduced dorsal stream connectivity in autism was only in part confirmed. Functional connectivity with superior parietal areas was not significantly reduced. However, the autism group showed significantly reduced connectivity with bilateral inferior frontal area 44, which is compatible with the hypothesis of mirror neuron defects in autism. More generally, our findings suggest that dorsal stream connectivity in autism may not be fully functional.