Seeing the forest and the trees: Disentangling autism phenotypes in the age of DSM-5.

This paper, written in honor of Professor Ed Zigler, focuses on some of the themes in developmental disabilities research that were so central to his work. It has now been nearly 80 years since Leo Kanner first identified the prototypic form - early infantile autism - of what is now autism spectrum disorder. In this article we summarize the development of the concept and the important accumulation of knowledge over time that has now led us to the recognition of a broader autism phenotype just as, at the same time, the current official diagnostic system in the USA has narrowed the concept. We also address current controversies regarding autism as the diagnosis is impacted by age and developmental factors, gender, and cultural issues. In parallel to the work on intellectual deficiency and development pioneered by Zigler and his colleagues, we summarize some of the challenges for the years ahead.

The role of limited salience of speech in selective attention to faces in toddlers with autism spectrum disorders.

BACKGROUND: Impaired attention to faces of interactive partners is a marker for autism spectrum disorder (ASD) in early childhood. However, it is unclear whether children with ASD avoid faces or find them less salient and whether the phenomenon is linked with the presence of eye contact or speech. METHODS: We investigated the impacts of speech (SP) and direct gaze (DG) on attention to faces in 22-month-old toddlers with ASD (n = 50) and typically developing controls (TD, n = 47) using the Selective Social Attention 2.0 (SSA 2.0) task. The task consisted of four conditions where the presence (+) and absence (-) of DG and SP were systematically manipulated. The severity of autism symptoms, and verbal and nonverbal skills were characterized concurrently with eye tracking at 22.4 (SD = 3.2) months and prospectively at 39.8 (SD = 4.3) months. RESULTS: Toddlers with ASD looked less than TD toddlers at face and mouth regions only when the actress was speaking (direct gaze absence with speech, DG-SP+: d = 0.99, p < .001 for face, d = 0.98, p < .001 for mouth regions; direct gaze present with speech, DG+SP+, d = 1.47, p < .001 for face, d = 1.01, p < .001 for mouth regions). Toddlers with ASD looked less at the eye region only when both gaze and speech cues were present (d = 0.46, p = .03). Salience of the combined DG and SP cues was associated concurrently and prospectively with the severity of autism symptoms, and the association remained significant after controlling for verbal and nonverbal levels. CONCLUSIONS: The study links poor attention to faces with limited salience of audiovisual speech and provides no support for the face avoidance hypothesis in the early stages of ASD. These results are consequential for research on early discriminant and predictive biomarkers as well as identification of novel treatment targets.

Temperamental markers in toddlers with autism spectrum disorder.

BACKGROUND: Although temperament has been recognized as an important contributor to childhood psychopathology, its role in emergent autism spectrum phenotypes is not well understood. This study examined whether toddlers with autism spectrum disorder (ASD) display temperamental vulnerabilities compared to toddlers with other developmental challenges, whether these characteristics are distinct from core autism symptoms, if they are stable over time, and if they contribute to social outcomes in preschool. METHODS: Parents of 165 toddlers with ASD, 58 nonverbal ability- and chronological age- (CA) matched developmentally delayed (DD) toddlers, and 92 CA-matched typically developing (TD) toddlers completed the Toddler Behavior Assessment Questionnaire-Supplemental (TBAQ-S) at 26 months (SD = 6; Time 1). TBAQ-S data were also available for a subset of toddlers with ASD (n = 126) at 43 months (SD = 9; Time 2). RESULTS: Compared to the DD and TD groups, toddlers with ASD exhibited vulnerabilities within the Effortful Control domain as well as the Surgency domain. They also displayed greater Negative Emotionality compared to TD peers. In the ASD group, temperamental characteristics were not concurrently related to autism severity or developmental level and individual differences were highly stable over time. Changes in Perceptual Sensitivity, Inhibitory Control, and Low-Intensity Pleasure from age 2 to 3.5 uniquely predicted autism symptom severity and adaptive social skill level at Time 2. CONCLUSIONS: Temperamental vulnerabilities in toddlers with ASD are stable over time and involve attentional and behavioral control as well as affective reactivity. They contribute uniquely to social outcomes in preschool and are likely to signal risk for developing later maladaptive attentional, affective, and behavioral symptoms. Considering biologically based dimensions may shed light on noncore facets of the early ASD phenotype that are potentially relevant to the emergence of comorbid conditions later in childhood.

Diagnostic stability in young children at risk for autism spectrum disorder: a baby siblings research consortium study.

BACKGROUND: The diagnosis of autism spectrum disorder (ASD) made before age 3 has been found to be remarkably stable in clinic- and community-ascertained samples. The stability of an ASD diagnosis in prospectively ascertained samples of infants at risk for ASD due to familial factors has not yet been studied, however. The American Academy of Pediatrics recommends intensive surveillance and screening for this high-risk group, which may afford earlier identification. Therefore, it is critical to understand the stability of an ASD diagnosis made before age 3 in young children at familial risk. METHODS: Data were pooled across seven sites of the Baby Siblings Research Consortium. Evaluations of 418 later-born siblings of children with ASD were conducted at 18, 24, and 36 months of age and a clinical diagnosis of ASD or Not ASD was made at each age. RESULTS: The stability of an ASD diagnosis at 18 months was 93% and at 24 months was 82%. There were relatively few children diagnosed with ASD at 18 or 24 months whose diagnosis was not confirmed at 36 months. There were, however, many children with ASD outcomes at 36 months who had not yet been diagnosed at 18 months (63%) or 24 months (41%). CONCLUSIONS: The stability of an ASD diagnosis in this familial-risk sample was high at both 18 and 24 months of age and comparable with previous data from clinic- and community-ascertained samples. However, almost half of the children with ASD outcomes were not identified as being on the spectrum at 24 months and did not receive an ASD diagnosis until 36 months. Thus, longitudinal follow-up is critical for children with early signs of social-communication difficulties, even if they do not meet diagnostic criteria at initial assessment. A public health implication of these data is that screening for ASD may need to be repeated multiple times in the first years of life. These data also suggest that there is a period of early development in which ASD features unfold and emerge but have not yet reached levels supportive of a diagnosis.

Early executive functioning predicts externalizing problems in neurodiverse preschoolers.

Children with autism spectrum disorder (ASD) often exhibit externalizing problems, which have been linked with increased anxiety and depression, peer rejection, and parental stress. Identification of early predictors of externalizing behaviors in autism will facilitate identification of vulnerable children and implementation of early preventative interventions. There is ample evidence that executive functioning, social functioning, and temperament are predictive of later externalizing problems in general populations, but less is known about these relations in ASD and other neurodiverse populations, particularly in the early preschool years. To address this gap, we assessed the relations between executive functioning, social functioning, and temperament at age 3 and externalizing problems at age 5 in a sample of neurodiverse children with ASD and other neurodevelopmental disorders and delays. Analyses revealed that severity of early executive functioning impairment predicted increased externalizing problems. Severity of social autism symptoms moderated this relationship such that the effect of executive functioning on externalizing problems decreased as autism symptoms increased. These findings suggest that executive functioning is an important target for identifying and developing interventions for vulnerable children and underscore the necessity of considering severity of autism symptoms when researching the development of externalizing problems in children with neurodevelopmental disorders.

Attend Less, Fear More: Elevated Distress to Social Threat in Toddlers With Autism Spectrum Disorder.

Differential emotional reactivity to social and nonsocial stimuli has been hypothesized but rarely examined empirically in ASD despite its potential importance for development of social motivation, cognition, and comorbid psychopathology. This study examined emotional reactivity, regulation, and attention to social and nonsocial threat in toddlers with ASD (n = 42, Mage : 22 months) and typically developing (TD) toddlers (n = 22, Mage : 23 months), and their mutual associations with autism symptom severity. Participants were exposed to social (stranger), nonsocial (mechanical objects), and ambiguous (masks) threats, and their intensity of distress (iDistress), attention to threat (Attention), and presence of emotion regulation (ER) strategies were measured. Autism symptom severity was quantified using the Autism Diagnostic Observation Schedule-2. In response to social threat, toddlers with ASD exhibited elevated iDistress (P < 0.038) but lower Attention (P < 0.002) and a wider variety of ER strategies (P < 0.040) compared to TD controls, though their ER strategies were less likely to be social. However, nonsocial and ambiguous threat elicited lower iDistress in ASD than in TD toddlers (P = 0.012 and P = 0.034, respectively), but comparable Attention and ER strategy use. Autism severity was not associated with iDistress. The study demonstrates elevated emotional salience but diminished attentional salience of social threat in ASD. A failure to attend adequately to social threats may restrict opportunities to appraise their threat value and engender often observed in ASD negative emotional responses to novel social situations. Early atypical emotional reactivity may independently contribute to the shaping of complex autism phenotypes and may be linked with later emerging affective and behavioral symptoms. LAY SUMMARY: Compared to typically developing toddlers, toddlers with ASD show diminished attention yet enhanced distress in response to social threat. Poor attention to potential social threat may limit opportunities to assess its threat value and thus contribute to often observed negative emotional responses to novel social situations. Identifying the precursors of atypical emotional reactivity in infancy and its links with later psychopathology will inform about novel treatment targets and mechanisms of change in the early stages of ASD. Autism Res 2021, 14: 1025-1036. © 2020 International Society for Autism Research, Wiley Periodicals, LLC.

Promoting social attention in 3-year-olds with ASD through gaze-contingent eye tracking.

Young children with autism spectrum disorder (ASD) look less toward faces compared to their non-ASD peers, limiting access to social learning. Currently, no technologies directly target these core social attention difficulties. This study examines the feasibility of automated gaze modification training for improving attention to faces in 3-year-olds with ASD. Using free-viewing data from typically developing (TD) controls (n = 41), we implemented gaze-contingent adaptive cueing to redirect children with ASD toward normative looking patterns during viewing of videos of an actress. Children with ASD were randomly assigned to either (a) an adaptive Cue condition (Cue, n = 16) or (b) a No-Cue condition (No-Cue, n = 19). Performance was examined at baseline, during training, and post-training, and contrasted with TD controls (n = 23). Proportion of time looking at the screen (%Screen) and at actresses' faces (%Face) was analyzed. At Pre-Training, Cue and No-Cue groups did not differ in %Face (P > 0.1). At Post-Training, the Cue group had higher %Face than the No-Cue group (P = 0.015). In the No-Cue group %Face decreased Pre- to Post-Training; no decline was observed in the Cue group. These results suggest gaze-contingent training effectively mitigated decreases of attention toward the face of onscreen social characters in ASD. Additionally, larger training effects were observed in children with lower nonverbal ability, suggesting a gaze-contingent approach may be particularly relevant for children with greater cognitive impairment. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions. Autism Res 2020, 13: 61-73. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we leverage a new technology that combines eye tracking and automatic computer programs to help very young children with ASD look at social information in a more prototypical way. In a randomized controlled trial, we show that the use of this technology prevents the diminishing attention toward social information normally seen in children with ASD over the course of a single experimental session. This work represents development toward new social attention therapeutic systems that could augment current behavioral interventions.

Operationalizing atypical gaze in toddlers with autism spectrum disorders: a cohesion-based approach.

Background: Multiple eye-tracking studies have highlighted the "atypical" nature of social attention in autism. However, it is unclear how "atypical" or "typical" should be quantified. Methods: We developed a method for identifying moments when members of a group looked at similar places (High-Cohesion Time Frames; HCTFs). We defined typicality as the proximity of gaze points to typically developing (TD) gaze points during TD HCTFs. Comparing toddlers with ASD (n = 112) to developmentally delayed (DD, n = 36) and TD (n = 163) toddlers during a video with Dyadic Bid, Sandwich-Making, Joint Attention, and Animated Toys conditions, we examined (a) individual typicality scores, (b) the relationship between typicality and symptom severity, and (c) HCTF distributions associated with each diagnostic group. Results: The ASD group had lower gaze typicality scores compared to the TD and DD groups in the Dyadic Bid and Sandwich-Making conditions but not during Animated Toys. The DD and TD groups did not differ in any condition. Correlational analyses indicated that higher typicality scores were associated with increased looking at pre-planned locations of the scene indexed by each experimental condition. In the ASD group, lower gaze typicality was associated with more severe autism symptoms. Examining ASD HCTFs, the gaze of toddlers with ASD was least cohesive during Dyadic Bid and most cohesive during Animated Toys. Conclusion: In contrast to non-ASD groups, toddlers with ASD show high cohesion during salient nonsocial events, suggesting that consistency in looking strategies may depend more on perceptual features. These findings are consequential for understanding individual differences in visual attention in ASD and for the design of more sensitive biomarker tasks for stratification, between-group differentiation, and measuring response to treatment.

Do Parents and Clinicians Agree on Ratings of Autism-Related Behaviors at 12 Months of Age? A Study of Infants at High and Low Risk for ASD.

Given the emphasis on early screening for ASD, it is crucial to examine the concordance between parent report and clinician observation of autism-related behaviors. Similar items were compared from the First Year Inventory (Baranek et al. First-Year Inventory (FYI) 2.0. University of North Carolina, Chapel Hill, 2003), a parent screener for ASD, and the ADOS-2 Toddler Module (Lord et al. 2013), a standardized ASD diagnostic tool. Measures were administered concurrently to 12-month-olds at high and low risk for ASD. Results suggest that clinicians and parents rated behaviors similarly. In addition, both informants rated high-risk infants as more impaired in several social-communication behaviors. Furthermore, the format of questions impacted agreement across observers. These findings have implications for the development of a new generation of screening instruments for ASD.

Electrodermal and behavioral responses of children with autism spectrum disorders to sensory and repetitive stimuli.

Parents frequently report that their children with autism spectrum disorders (ASD) respond atypically to sensory stimuli. Repetitive behaviors are also part of the ASD behavioral profile. Abnormal physiological arousal may underlie both of these symptoms. Electrodermal activity (EDA) is an index of sympathetic nervous system arousal. The goals of this study were twofold: (1) to pilot methods for collecting EDA data in young children and (2) to examine hypothesized relationships among EDA, and sensory symptoms and repetitive behaviors in children with ASD as compared with children with typical development. EDA was recorded on 54 young children with ASD and on 33 children with typical development (TD) during a protocol that included baseline, exposure to sensory and repetitive stimuli, and play. Parents completed standardized questionnaires regarding their child's sensory symptoms and repetitive behaviors. Frequency and type of repetitive behavior during play was coded offline. Comparisons between EDA data for ASD and TD groups indicated no significant between-group differences in any measures. Parents of children with ASD reported more abnormal responses to sensory stimuli and more repetitive behaviors, but scores on these measures were not significantly correlated with EDA or with frequency of observed repetitive behaviors. Parent report of frequency and severity of sensory symptoms was significantly correlated with reports of repetitive behaviors in both groups. Although parents of children with ASD report high levels of sensory symptoms and repetitive behaviors, these differences are not related to measured EDA arousal or reactivity.

Predicting developmental status from 12 to 24 months in infants at risk for Autism Spectrum Disorder: a preliminary report.

The study examined whether performance profiles on individual items of the Toddler Module of the Autism Diagnostic Observation Schedule at 12 months are associated with developmental status at 24 months in infants at high and low risk for developing Autism Spectrum Disorder (ASD). A nonparametric decision-tree learning algorithm identified sets of 12-month predictors of developmental status at 24 months. Results suggest that identification of infants who are likely to exhibit symptoms of ASD at 24 months is complicated by variable patterns of symptom emergence. Fine-grained analyses linking specific profiles of strengths and deficits with specific patterns of symptom emergence will be necessary for further refinement of screening and diagnostic instruments for ASD in infancy.