Validation of the Electronic Modified Checklist for Autism in Toddlers, Revised with Follow-Up: A Nonrandomized Controlled Trial.

OBJECTIVE: To examine the classification rates and screening properties, including sensitivity and specificity, of the web-based Modified Checklist for Autism in Toddler, Revised with Follow-Up (M-CHAT-R/F) compared with paper-phone administration, and to determine the extent to which electronic M-CHAT-R/F streamlines screening, increases screening fidelity, increases diagnostic evaluation participation, and decreases waiting time from screening to evaluation compared with paper-phone modality. STUDY DESIGN: Primary-care practices in urban and suburban settings administered either the web-based or paper-phone M-CHAT-R/F using a prospective nonrandomized control design. Toddlers (n = 17 900) were screened between 2009 and 2016 at routine well-child check-ups. Toddlers who screened at risk on the M-CHAT-R/F were invited to complete diagnostic evaluations; 176 children were diagnosed with autism. The χ2, Fisher exact, and t-tests, as well as regression and screening properties, were used to compare outcome distributions, screening properties, and implementation by modality. RESULTS: Classification rates of the initial M-CHAT-R into low, medium, and high risk were significantly different across modalities with very small effect sizes. Sensitivity and specificity were high across both modalities. For children in the medium-risk range, the web-based modality had a greater rate of predicting risk for autism after Follow-Up compared with the paper-phone modality, and the web eliminated delay between initial screen and Follow-Up. The web-based modality showed increased screening fidelity, no data loss, and similar rates of evaluation attendance and time to evaluation from Follow-Up administration. CONCLUSIONS: The web-based M-CHAT-R/F is a valid tool for universal autism screening. Systems-level decisions should balance the increased feasibility of the electronic administration with the increase in Follow-Up accuracy provided by skilled clinician interview.

Expert consensus regarding indicators of a traumatic reaction in autistic youth: a Delphi survey.

OBJECTIVE: It has been suggested that the sequelae of trauma are under-recognized in youth on the autism spectrum. We aimed to generate expert consensus regarding important trauma indicators, including but not limited to traumatic stress symptoms, in autistic youth. METHODS: We recruited 72 experts in autism and/or childhood trauma. Via a 2-round Delphi survey, experts commented on and rated the importance of 48 potential indicators, drawn from PTSD criteria and a broader literature on traumatic sequelae in autism. A revised list of 51 indicators, 18 clinical guidelines developed from expert comments, and summaries of expert qualifications and ratings from Round 1 were submitted to a second round (n = 66; 92% retention) of expert review and rating. RESULTS: Twenty-two indicators reached consensus (>75% round 2 endorsement). Many, but not all, reflected PTSD criteria, including intrusions (e.g., trauma re-enactments in perseverative play/speech), avoidance of trauma-reminders, and negative alterations in mood/cognition (e.g., diminished interest in activities) and in arousal/reactivity (e.g., exaggerated startle). Experts also identified increased reliance on others, adaptive and language regressions, self-injurious behavior, and non-suicidal self-injury as important indicators. Consensus guidelines emphasized the need for tailored measures, developmentally informed criteria, and multiple informants to increase diagnostic accuracy. CONCLUSIONS: Expert consensus emphasizes and informs a need for tailored diagnostic guidelines and measures to more sensitively assess traumatic reactions in autistic youth.

White matter pathways associated with empathy in females: A DTI investigation.

Empathy is a component of social cognition that allows us to understand, perceive, experience, and respond to the emotional state of others. In this study, we seek to build on previous research that suggests that sex and hormone levels may impact white matter microstructure. These white matter microstructural differences may influence social cognition. We examine the fractional anisotropy (FA) of white matter pathways associated with the complex human process of empathy in healthy young adult females during the self-reported luteal phase of their menstrual cycle. We used tract-based spatial statistics to perform statistical comparisons of FA and conducted multiple linear regression analysis to examine the strength of association between white matter FA and scores on the Empathy Quotient (EQ), a self-report questionnaire in which individuals report how much they agree or disagree with 60 statements pertaining to their empathic tendencies. Results identified a significant negative relationship between EQ scores and FA within five clusters of white matter: in the left forceps minor/body of the corpus callosum, left corticospinal tract, intraparietal sulcus/primary somatosensory cortex, superior longitudinal fasciculus, and right inferior fronto-occipital fasciculus/forceps minor. These consistent findings across clusters suggest that lower self-reported empathy is related to higher FA across healthy young females in specific white matter regions during the menstrual luteal phase. Future research should seek to examine if self-reported empathy varies across the menstrual cycle, using blood samples to confirm cycle phase and hormone levels.

Early and Repeated Screening Detects Autism Spectrum Disorder.

OBJECTIVE: To evaluate timing and accuracy of early and repeated screening for autism spectrum disorder (ASD) during well-child visits. STUDY DESIGN: Using a longitudinal study design, toddlers (n = 5784) were initially screened at 12 (n = 1504), 15 (n = 1228), or 18 (n = 3052) months during well-child visits, and rescreened at 18, 24, and 36 months. Of those screened, 368 toddlers attended an ASD evaluation after a positive screen and/or a provider concern for ASD at any visit. RESULTS: Screens initiated at 12 months yielded an ASD diagnosis significantly earlier than at 15 months (P = .003, d = 0.99) and 18 months (P < .001, d = 0.97). Cross-group overall sensitivity of the initial screen was .715 and specificity was .959. Repeat screening improves sensitivity (82.1%), without notably decreasing specificity (all >93.5%). Screening at 18 months resulted in significantly higher positive predictive value than at 12 months (X2 (1, n = 221) = 9.87, P = .002, OR = 2.60) and 15 months (X2 (1, n = 208) = 14.57, P < .001, OR = 3.67). With repeat screening, positive predictive value increased for all screen groups, but the increase was not significant. CONCLUSIONS: Screening as early as 12 months effectively identifies many children at risk for ASD. Children screened at 12 months receive a diagnosis of ASD significantly earlier than peers who are first screened at later ages, facilitating earlier intervention. However, as the sensitivity is lower for a single screen, screening needs to be repeated.

A novel social attribution paradigm: The Dynamic Interacting Shape Clips (DISC).

The Dynamic Interacting Shape Clips (DISC) is a novel stimulus set designed to examine mentalizing, specifically social attribution, suitable for use with diverse methodologies including fMRI. The DISC offer some advantages compared to other social attribution stimuli including a large number of stimuli, subsets of stimuli depicting different kinds of social interactions (i.e., friendly approach, aggression, and avoidance), and two control tasks-one that contrasts interpretations of socially contingent movement versus random, inanimate movement, and the other that examines the impact of attentional shifts on mentalizing using the same visual stimuli with a different cue. This study describes both behavioral and fMRI findings from a sample of 22 typically developing adults (mage = 21.7 years, SD = 1.72). Behavioral data supports participants anthropomorphized the stimuli and the social intent of the clips were perceived as intended. Neuroimaging findings demonstrate that brain areas associated with processing animacy and mental state attribution were activated when participants were shown clips featuring social interactions compared to random movement, and when attention was cued to social versus physical aspects of the same stimuli. Results lend empirical support for the use of the DISC in future studies of social cognition.

An Expanded View of Joint Attention: Skill, Engagement, and Language in Typical Development and Autism.

This study provides an expanded view of joint attention and its relation to expressive language development. A total of 144 toddlers (40 typically developing, 58 with autism spectrum disorder [ASD], 46 with developmental delay [DD]) participated at 24 and 31 months. Toddlers who screened positive for ASD risk, especially those subsequently diagnosed with ASD, had poorer joint attention skills, joint engagement during parent-toddler interaction, and expressive language. Findings highlight the dynamic relation between joint attention and language development. In the ASD and DD groups, joint engagement predicted later expressive vocabulary, significantly more than predictions based on joint attention skills. Joint engagement was most severely impacted when toddlers did not talk initially and improved markedly if they subsequently began to speak.

Risk Assessment for Parents Who Suspect Their Child Has Autism Spectrum Disorder: Machine Learning Approach.

BACKGROUND: Parents are likely to seek Web-based communities to verify their suspicions of autism spectrum disorder markers in their child. Automated tools support human decisions in many domains and could therefore potentially support concerned parents. OBJECTIVE: The objective of this study was to test the feasibility of assessing autism spectrum disorder risk in parental concerns from Web-based sources, using automated text analysis tools and minimal standard questioning. METHODS: Participants were 115 parents with concerns regarding their child's social-communication development. Children were 16- to 30-months old, and 57.4% (66/115) had a family history of autism spectrum disorder. Parents reported their concerns online, and completed an autism spectrum disorder-specific screener, the Modified Checklist for Autism in Toddlers-Revised, with Follow-up (M-CHAT-R/F), and a broad developmental screener, the Ages and Stages Questionnaire (ASQ). An algorithm predicted autism spectrum disorder risk using a combination of the parent's text and a single screening question, selected by the algorithm to enhance prediction accuracy. RESULTS: Screening measures identified 58% (67/115) to 88% (101/115) of children at risk for autism spectrum disorder. Children with a family history of autism spectrum disorder were 3 times more likely to show autism spectrum disorder risk on screening measures. The prediction of a child's risk on the ASQ or M-CHAT-R was significantly more accurate when predicted from text combined with an M-CHAT-R question selected (automatically) than from the text alone. The frequently automatically selected M-CHAT-R questions that predicted risk were: following a point, make-believe play, and concern about deafness. CONCLUSIONS: The internet can be harnessed to prescreen for autism spectrum disorder using parental concerns by administering a few standardized screening questions to augment this process.

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin.

Associations between autistic traits and fractional anisotropy values in white matter tracts in a nonclinical sample of young adults.

Whereas a number of studies have examined relationships among brain activity, social cognitive skills, and autistic traits, fewer studies have evaluated whether structural connections among brain regions relate to these traits and skills. Uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF) are white matter tracts that may underpin the behavioral expression of these skills because they connect regions within or provide sensory information to brain areas implicated in social cognition, and structural differences in these tracts have been associated with autistic traits. We examined relationships among self-reported autistic traits, mentalizing, and water diffusivity in UF and ILF in a nonclinical sample of 24 young adults (mean age = 21.92 years, SD = 4.72 years; 15 women). We measured autistic traits using the Autism-Spectrum Quotient, and we measured mentalizing using the Dynamic Interactive Shapes Clips task. We used Tract-Based Spatial Statistics and randomize to examine relationships among fractional anisotropy (FA) values in bilateral ILF and UF, age, cognitive abilities, autistic traits, and mentalizing. Autistic traits were positively related to FA values in left ILF. No other relationships between FA values and other variables were significant. Results suggest that left ILF may be involved in the expression of autistic traits in individuals without clinical diagnoses.

Adding sound to theory of mind: Comparing children's development of mental-state understanding in the auditory and visual realms.

Theory of mind (ToM) gradually develops during the preschool years. Measures of ToM usually target visual experience, but auditory experiences also provide valuable social information. Given differences between the visual and auditory modalities (e.g., sights persist, sounds fade) and the important role environmental input plays in social-cognitive development, we asked whether modality might influence the progression of ToM development. The current study expands Wellman and Liu's ToM scale (2004) by testing 66 preschoolers using five standard visual ToM tasks and five newly crafted auditory ToM tasks. Age and gender effects were found, with 4- and 5-year-olds demonstrating greater ToM abilities than 3-year-olds and girls passing more tasks than boys; there was no significant effect of modality. Both visual and auditory tasks formed a scalable set. These results indicate that there is considerable consistency in when children are able to use visual and auditory inputs to reason about various aspects of others' mental states.

Autism research capacity building in Northern Mexico: Preliminary evaluation of an ongoing process.

LAY ABSTRACT: To inform improvement of care and public policy, quality research is required. Conducting research projects requires skills and infrastructure. Research capacity building is the process by which individuals and organizations develop greater ability to conduct useful research. However, in the scientific community, research quality and productivity measures are often focused on long-term products, such as publications or grants awarded. Those measures are not helpful when measuring initial stages of research, a common situation in low- and middle-income countries. We used a six-principle framework designed by J. Cooke to assess the progress of an autism research collaborative in northern Mexico. We established 64 criteria across the six principles, and rated them as Not Started, In Progress, or Achieved, based on narratives and process documentation collected for this purpose. Ratings were established for the Years 2018, 2020, and 2022. The principles with the highest Achieved rates were "Linkages, collaborations, and partnerships" (90%), and "Infrastructure" (Principle 6, 70%). Cooke's research capacity building framework is a useful way to monitor progress of research capacity building and contribute to harmonious development of relevant principles at different levels.

Categorizing and identifying preferred interests in autistic toddlers.

Preferred interests are characteristic of autism spectrum disorder and are reported by parents starting at an early age. However, limited research has explored the presentation of preferred interests in toddlerhood. Previous literature suggests that both the intensity and type of preferred interests held by autistic individuals differ from those held by peers with developmental delay and no diagnosis and that autistic interests are more unusual in nature. While preferred interests are seen in typical child development, previous research suggests that the presence of preferred interests in children with no diagnosis declines with age. Literature also indicates that the sex and cognitive ability of autistic children influences preferred interests. Identification of early preferred interests commonly held by autistic toddlers could serve as a useful clinical indicator of future diagnosis. This article explored whether diagnostic group, age, sex, and cognitive ability predict the likelihood that parents reported preferred interests in children aged 12-36 months with diagnoses of autism, developmental delay, and those with no diagnosis. Additionally, we explored potential diagnostic group differences in interest type. Results suggest that diagnostic group, but not age, sex, or cognitive ability, predicts the likelihood that parents report preferred interests. No differences in the type of interests among diagnostic groups were identified. These results support the use of preferred interests as an early sign of autism but suggest that interest type may not be a helpful clinical indicator of autism in toddlerhood.

Role of Primary Care Clinician Concern During Screening for Early Identification of Autism.

OBJECTIVE: The aim of this study was to evaluate the added value of primary care clinician (PCC)-indicated concern during primary care universal standardized screening in early identification of autism. METHODS: Toddlers were screened for autism during primary care checkups (n = 7,039, aged 14.24-22.43 months) in 2 studies. Parents completed the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up. For each participant, PCCs indicated whether they had autism concerns (optional in 1 study-before or after viewing screening results, required before viewing screen results in the other). Children at high likelihood for autism from screen result and/or PCC concern (n = 615) were invited for a diagnostic evaluation; 283 children attended the evaluation. RESULTS: Rates of PCC-indicated autism concerns were similar whether PCCs were required or encouraged to indicate concerns. High likelihood of autism indication on both screen and PCC concern resulted in the highest positive predictive value for autism and positive predictive value for any developmental disorder, as well as the highest evaluation attendance, with no significant difference between the positive screen-only and PCC concern-only groups. Although the frequency of PCC-indicated autism concern did not differ significantly based on the child's cognitive level, PCCs were more likely to identify children with more obvious autism characteristics compared with more subtle autism characteristics as having autism. CONCLUSION: The findings support the recommendation of the American Academy of Pediatrics that both screening and surveillance for autism be incorporated into well-child visits. High likelihood of autism on either screen or PCC concern should trigger a referral for an evaluation.

Development of a school-age extension of the Modified Checklist for Autism in Toddlers through expert consensus and stakeholder input.

LAY ABSTRACT: The American Academy of Pediatrics recommends universal screening to identify children at higher likelihood for autism at 18- and 24-month well-child visits. There are many children, however, that are missed during this toddler age who do not get diagnosed until much later in development, delaying access to autism-specific interventions. Currently, brief measures for universal autism screening for school-age children, however, are lacking. In this project, we adapted a commonly used autism screener for toddlers, the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up (M-CHAT-R/F), to be used for school-age children. This measure, called the M-CHAT-School (M-CHAT-S), is a parent- and teacher-report questionnaire to be used to screen for autism in school-age children aged 4 to 8 years of age. M-CHAT-S was developed through feedback from autism experts, as well as interviews with parents and teachers to provide input on the items. Two versions of M-CHAT-S were developed, one for verbally fluent and one for minimally verbal school-age children. M-CHAT-S is a brief measure, with updated items to reflect changes in the way experts think and talk about autism, making it a useful measure to use for autism screening in elementary aged children. The next steps include further testing to ensure that M-CHAT-S performs well in identifying children with increased likelihood of autism, after which it will be made available to parents, educators, and other professionals.

Accuracy of initial diagnostic impressions of autism in toddlers and behaviors that inform these impressions.

Clinicians form initial impressions about a child's diagnosis based on behavioral features, but research has not yet identified specific behaviors to guide initial diagnostic impressions. Participants were toddlers (N = 55, mean age 22.9 months) from a multi-site early detection study, referred for concern for ASD due to screening or parent/provider concern. Within 5 min of meeting a child, clinicians noted ASD or non-ASD impression, confidence in impression, and behaviors that informed their impression. These clinicians also determined final diagnoses for each child. When a child's final diagnosis was ASD (n = 35), senior clinicians formed an initial impression of ASD in 22 cases (63%) but missed 13 cases (37%). When final diagnosis was non-ASD (n = 20), senior clinicians made an initial impression of non-ASD in all cases (100%). Results were similar among junior clinicians. Senior and junior clinicians used the same behaviors to form accurate impressions of ASD and non-ASD: social reciprocity, nonverbal communication, and eye contact. Senior clinicians additionally used focus of attention when forming accurate impressions of ASD and non-ASD; junior clinicians used this behavior only when forming accurate non-ASD impressions. Clinicians' initial impressions of ASD are very likely to be consistent with final diagnoses, but initial impressions of non-ASD need follow-up. Toddlers who show all four atypical behaviors (social reciprocity, nonverbal communication, eye contact, and focus of attention) might receive expedited ASD diagnoses. However, presence of apparently typical behaviors should not rule out ASD; for some children a longer evaluation is necessary to allow for more opportunities to observe subtle social behavior.

Undifferentiated facial electromyography responses to dynamic, audio-visual emotion displays in individuals with autism spectrum disorders.

We examined facial electromyography (fEMG) activity to dynamic, audio-visual emotional displays in individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals. Participants viewed clips of happy, angry, and fearful displays that contained both facial expression and affective prosody while surface electrodes measured corrugator supercilli and zygomaticus major facial muscle activity. Across measures of average and peak activity, the TD group demonstrated emotion-selective fEMG responding, with greater relative activation of the zygomatic to happy stimuli and greater relative activation of the corrugator to fearful stimuli. In contrast, the ASD group largely showed no significant differences between zygomatic and corrugator activity across these emotions. There were no group differences in the magnitude and timing of fEMG response in the muscle congruent to the stimuli. This evidence that fEMG responses in ASD are undifferentiated with respect to the valence of the stimulus is discussed in light of potential underlying neurobiological mechanisms.

Autistic children who create imaginary companions: Evidence of social benefits.

LAY ABSTRACT: Research on neurotypical children with imaginary friends has found that those with imaginary friends have better social skills and are more able to think about how other people's minds work compared to children without imaginary friends. Research shows that some autistic children also create imaginary friends. This article is the first to look at whether or not autistic children with imaginary friends have stronger social skills and an improved ability to think about others' minds than those without imaginary friends. We asked parents to report about their children aged 5 to 12. Finding almost half reported their child had an imaginary friend, a much larger number than previous research with younger children. Our findings also suggested that autistic children with imaginary friends were better able to understand others' minds and had stronger social skills than their peers without imaginary friends. The children's language ability did not influence this. The findings of this study add to the evidence that with respect to the creation imaginary friends and their potential benefits, the play profiles of autistic children are similar to the general population. It also provides more evidence that the understanding of others' minds is not all or nothing in autism and gives reason for researchers to investigate whether the causes of these differences are the same or different for autistic children.

Sensitivity and Specificity of the Modified Checklist for Autism in Toddlers (Original and Revised): A Systematic Review and Meta-analysis.

Importance: The Modified Checklist for Autism in Toddlers (M-CHAT) and the M-CHAT, Revised With Follow-up (M-CHAT-R/F)-henceforth referred to as M-CHAT(-R/F)-are the most commonly used toddler screeners for autism spectrum disorder (ASD). Their use often differs from that in the original validation studies, resulting in a range of estimates of sensitivity and specificity. Also, given the variability in reports of the clinical utility of the M-CHAT(-R/F), researchers and practitioners lack guidance to inform autism screening protocols. Objective: To synthesize variability in sensitivity and specificity of M-CHAT(-R/F) across multiple factors, including procedures for identifying missed cases, likelihood level, screening age, and single compared with repeated screenings. Data Sources: A literature search was conducted with PubMed, Web of Science, and Scopus to identify studies published between January 1, 2001, and August 31, 2022. Study Selection: Articles were included if the studies used the M-CHAT(-R/F) (ie, original or revised version) to identify new ASD cases, were published in English-language peer-reviewed journals, included at least 10 ASD cases, reported procedures for false-negative case identification, screened children by 48 months, and included information (or had information provided by authors when contacted) needed to conduct the meta-analysis. Data Extraction and Synthesis: The systematic review and meta-analysis was conducted within the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The Quality Assessment of Diagnostic Accuracy Studies-2 tool evaluated bias in sample selection. Data extraction and quality assessment were performed by 2 authors independently. The overall diagnostic accuracy of the M-CHAT(-R/F) was assessed with the hierarchic summary receiver operating characteristic (HSROC) model. Main Outcomes and Measures: Sensitivity, specificity, diagnostic odds ratios, and HSROC curves of M-CHAT(-R/F). Results: The review included 50 studies with 51 samples. The pooled sensitivity of M-CHAT(-R/F) was 0.83 (95% CI, 0.77-0.88), and the pooled specificity was 0.94 (95% CI, 0.89-0.97). Heterogeneity analyses revealed greater diagnostic accuracy for low- vs high-likelihood samples, a concurrent vs prospective case confirmation strategy, a large vs small sample size, use of M-CHAT(-R/F) Follow-up, and non-English vs English only. Conclusions and Relevance: Overall, results of this study suggest the utility of the M-CHAT(-R/F) as an ASD screener. The wide variability in psychometric properties of M-CHAT(-R/F) highlights differences in screener use that should be considered in research and practice.

Does Treatment Fidelity of the Early Start Denver Model Impact Skill Acquisition in Young Children with Autism?

There is increasing evidence supporting the effectiveness of the Early Start Denver Model (ESDM) for children on the autism spectrum. However, substantial variability in response to the ESDM has been reported across participants. We examined the plausible yet untested hypothesis that variations in the fidelity level of therapists delivering the intervention contribute to variability in children's response to the ESDM. Videotaped sessions (n = 40) of toddlers on the autism spectrum who received the ESDM from trained therapists were coded to obtain measures of therapist fidelity and children's learning in response to the therapists' instruction. Variations in overall fidelity, along with variations in most items included in the ESDM fidelity checklist, contributed to the children's learning response during the sessions.