Predictors of Suicidal Thoughts in Children with Autism Spectrum Disorder and Anxiety or Obsessive-Compulsive Disorder: The Unique Contribution of Externalizing Behaviors

Children with autism spectrum disorder (ASD) are at elevated risk of suicidal ideation, particularly those with comorbid anxiety disorders and/or obsessive-compulsive disorder (OCD). We investigated the risk factors associated with suicidal ideation in 166 children with ASD and comorbid anxiety disorders/OCD, and the unique contribution of externalizing behaviors. Suicidal ideation was reported in the child sample by 13% of parents. Controlling for child age, sex, and IQ, perceived loneliness positively predicted the likelihood of suicidal ideation. In addition, externalizing behaviors positively predicted suicidal ideation, controlling for all other factors. Reliance on parental report to detect suicidal ideation in youth with ASD is a limitation of this study. Nonetheless, these findings highlight the importance of assessing and addressing suicidal ideation in children with ASD and comorbid anxiety disorders/OCD, and more importantly in those with elevated externalizing behaviors and perceptions of loneliness.

Keywords: ASD; Anxiety; Externalizing behaviors; OCD; Suicidal thoughts.

Participation in research can provide direct and indirect benefit to individuals with autism spectrum disorder (ASD), their caregivers, families, and society at large. Unfortunately, individuals with high support needs, including those with intellectual disability, cognitive disability or minimal verbal ability, are often systematically excluded from research on ASD. This limits the ability to generalize discoveries to all people with ASD, and results in a disparity in who benefits from research. This piece outlines the importance and extent of the problem, which is part of a broader lack of inclusivity in ASD research. It also provides examples of studies that have directly addressed issues that arise when conducting inclusive research and makes recommendations for researchers to reduce disparities in research participation.

Keywords: Inclusion; Intellectual Disability; Participation; Research.

Autistic individuals who are also people of color or from lower socioeconomic strata are historically underrepresented in research. Lack of representation in autism research has contributed to health and healthcare disparities. Reducing these disparities will require culturally competent research that is relevant to under-resourced communities as well as collecting large nationally representative samples, or samples in which traditionally disenfranchised groups are over-represented. To achieve these goals, a diverse group of culturally competent researchers must partner with and gain the trust of communities to identify and eliminate barriers to participating in research. We suggest community-academic partnerships as one promising approach that results in high-quality research built on cultural competency, respect, and shared decision making.

Keywords: Autism; Engagement; Ethnicity; Participation; Race; Socioeconomic status

Awareness of autism has grown monumentally over the past 20 years. Yet, this increased awareness has not been accompanied by improvements in services to support autistic individuals and their families. Many fundamental questions remain about the care of people with autism—including which interventions are effective, for whom, when, and at what intensity. The Lancet Commission on the future of care and clinical research in autism aims to answer the question of what can be done in the next 5 years to address the current needs of autistic individuals and families worldwide

Background: Early identification of autism spectrum disorder (ASD) provides an opportunity for early intervention and improved developmental outcomes. The use of electroencephalography (EEG) in infancy has shown promise in predicting later ASD diagnoses and in identifying neural mechanisms underlying the disorder. Given the high co-morbidity with language impairment, we and others have speculated that infants who are later diagnosed with ASD have altered language learning, including phoneme discrimination. Phoneme learning occurs rapidly in infancy, so altered neural substrates during the first year of life may serve as early, accurate indicators of later autism diagnosis.

Methods: Using EEG data collected at two different ages during a passive phoneme task in infants with high familial risk for ASD, we compared the predictive accuracy of a combination of feature selection and machine learning models at 6 months (during native phoneme learning) and 12 months (after native phoneme learning), and we identified a single model with strong predictive accuracy (100%) for both ages. Samples at both ages were matched in size and diagnoses (n = 14 with later ASD; n = 40 without ASD). Features included a combination of power and nonlinear measures across the 10‑20 montage electrodes and 6 frequency bands. Predictive features at each age were compared both by feature characteristics and EEG scalp location. Additional prediction analyses were performed on all EEGs collected at 12 months; this larger sample included 67 HR infants (27 HR-ASD, 40 HR-noASD).

Results: Using a combination of Pearson correlation feature selection and support vector machine classifier, 100% predictive diagnostic accuracy was observed at both 6 and 12 months. Predictive features differed between the models trained on 6- versus 12-month data. At 6 months, predictive features were biased to measures from central electrodes, power measures, and frequencies in the alpha range. At 12 months, predictive features were more distributed between power and nonlinear measures, and biased toward frequencies in the beta range. However, diagnosis prediction accuracy substantially decreased in the larger, more behaviorally heterogeneous 12-month sample.

Conclusions: These results demonstrate that speech processing EEG measures can facilitate earlier identification of ASD but emphasize the need for age-specific predictive models with large sample sizes to develop clinically relevant classification algorithms.

Keywords: Autism; EEG; Infant; Language development; Machine learning; Sensitive period.

In this study we investigated the impact of parental language input on language development and associated neuroscillatory patterns in toddlers at risk of Autism Spectrum Disorder (ASD). Forty-six mother-toddler dyads at either high (n = 22) or low (n = 24) familial risk of ASD completed a longitudinal, prospective study including free-play, resting electroencephalography, and standardized language assessments. Input quantity/quality at 18 months positively predicted expressive language at 24 months, and relationships were stronger for high-risk toddlers. Moderated mediations revealed that input-language relationships were explained by 24-month frontal and temporal gamma power (30-50 Hz) for high-risk toddlers who would later develop ASD. Results suggest that high-risk toddlers may be cognitively and neurally more sensitive to their language environments, which has implications for early intervention.

Keywords: Autism; EEG; Early experience; Language development; Language input.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.

Background

Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection.

Methods

Data from the Infant Brain Imaging Study (n=94, 68 male) were used to examine 6-month cerebellar functional connectivity (fcMRI) in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning-based predictive tests examined cerebellar-frontoparietal (FPN; subserves error signaling in support of EBL) and cerebellar-default mode (DMN; broadly implicated in ASD) network connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven fcMRI enrichment examined brain-wide behavioral associations, with post-hoc tests of cerebellar connections.

Results

Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. fcMRI enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post-hoc tests did not suggest a role for cerebellar connections.

Conclusions

We failed to identify cerebellar functional connectivity-based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.

Keywords

Autismfunctional connectivitycerebelluminfancyerror-based learningdevelopment

Although studies of PAF in individuals with autism spectrum disorder (ASD) report group differences and associations with non-verbal cognitive ability, it is not known how PAF relates to familial risk for ASD, and whether similar associations with cognition in are present in infancy. Using a large multi-site prospective longitudinal dataset of infants with low and high familial risk for ASD, metrics of PAF at 12 months were extracted and growth curves estimated for cognitive development between 12-36 months. Analyses tested whether PAF 1) differs between low and high risk infants, 2) is associated with concurrent non-verbal/verbal cognitive ability and 3) predicts developmental change in non-verbal/verbal ability. Moderation of associations between PAF and cognitive ability by familial risk status was also tested. No differences in 12-month PAF were found between low and high risk infants. PAF was associated with concurrent non-verbal cognitive ability, but did not predict change in non-verbal cognitive over development. No associations were found between PAF and verbal ability, along with no evidence of moderation. PAF is not related to familial risk for ASD, and is a neural marker of concurrent non-verbal cognitive ability, but not verbal ability, in young infants at low and high risk for ASD.

Keywords: Autism spectrum disorder; Cognitive development; EEG; Infant siblings; Peak alpha frequency.

Objective: To examine the emergence and trajectory of feeding difficulties in young children who are later diagnosed with autism spectrum disorder (ASD).

Methods: The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was administered to a sample of 93 toddlers with an older sibling with ASD-the high-risk group-and 62 toddlers with no known familial ASD-the low-risk group-as part of a larger infant sibling study. The BPFAS was completed by parents at 15, 18, 24, and 36 months of age. At 36 months, participants underwent a diagnostic assessment and were classified into 1 of the following 4 outcome groups: ASD, nontypical development, high-risk typically developing, and low-risk typically developing. The BPFAS was scored for total frequency of feeding difficulties and autism-specific factor scores previously described in the literature.

Results: The frequency of feeding difficulties increased significantly more rapidly in the ASD group between 15 and 36 months of age, and by 36 months, they exhibited a significantly higher total frequency score than all other groups. Analysis of the factor scores revealed a similar pattern for the food acceptance and mealtime behavior domains but no significant differences in the medical/oral motor domain.

Conclusion: Feeding difficulties develop significantly more rapidly in children with ASD, with longitudinal monitoring revealing the steeper trajectory earlier than can be detected with cross-sectional analysis. Children with ASD are at risk of health and social consequences of poor feeding behavior that may potentially be minimized if addressed early and appropriately.

Background: Recent large-scale initiatives have led to systematically collected phenotypic data for several rare genetic conditions implicated in autism spectrum disorder (ASD). The onset of developmentally expected skills (e.g. walking, talking) serve as readily quantifiable aspects of the behavioral phenotype. This study’s aims were: (a) describe the distribution of ages of attainment of gross motor and expressive language milestones in several rare genetic conditions, and (b) characterize the likelihood of delays in these conditions compared with idiopathic ASD.

Methods: Participants aged 3 years and older were drawn from two Simons Foundation Autism Research Initiative registries that employed consistent phenotyping protocols. Inclusion criteria were a confirmed genetic diagnosis of one of 16 genetic conditions (Simons Searchlight) or absence of known pathogenic genetic findings in individuals with ASD (SPARK). Parent-reported age of acquisition of three gross motor and two expressive language milestones was described and categorized as on-time or delayed, relative to normative expectations.

Results: Developmental milestone profiles of probands with genetic conditions were marked by extensive delays (including nonattainment), with highest severity in single gene conditions and more delays than idiopathic ASD in motor skills. Compared with idiopathic ASD, the median odds of delay among the genetic groups were higher by 8.3 times (IQR 5.8-16.3) for sitting, 12.4 times (IQR 5.3-19.5) for crawling, 26.8 times (IQR 7.7-41.1) for walking, 2.7 times (IQR 1.7-5.5) for single words, and 5.7 times (IQR 2.7-18.3) for combined words.

Conclusions: Delays in developmental milestones, particularly in gross motor skills, are frequent and may be among the earliest indicators of differentially affected developmental processes in specific genetically defined conditions associated with ASD, as compared with those with clinical diagnoses of idiopathic ASD. The possibility of different developmental pathways leading to ASD-associated phenotypes should be considered when deciding how to employ specific genetic conditions as models for ASD.

Keywords: copy number variant; developmental phenotype; intellectual disability.

Environmental health, toxic chemicals, autism, environment