"On-Time Autism Intervention": A Diagnostic Practice Framework to Accelerate Access.

It is well-documented that autism can be reliably diagnosed by age two and that early signs emerge most often between 18 and 24 months. However, despite the increased awareness and focus on early diagnosis, the average age of diagnosis is over 4 years old; even later for Black children and those who are Medicaid-eligible. In this paper, we will propose a framework for accurate and accelerated autism diagnosis for children before age three. The proposed framework emphasizes a collaborative diagnostic process, which relies heavily on Birth to Three provider knowledge and expertise. Considerations for next steps are presented. This approach could increase access to diagnosis of young children soon after first signs of autism emerge.

The effect of early autism intervention on parental sense of efficacy in a randomized trial depends on the initial level of parent stress.

LAY ABSTRACT: This is a study of the secondary effects of interventions for young children with autism on their parents. Specifically, we were interested in the impact on parent's sense of efficacy, or how confident and competent a parent feels about themselves as a parent. We tested three ideas: (1) that the style of the intervention, whether it was more or less structured and whether the parent had a more or less formal role, would impact a parent's sense of efficacy; (2) that the intensity of the intervention, how many hours per week the intervention was delivered, would impact parental efficacy; and (3) that the parent's level of stress prior to intervention would impact how intensity and style effected efficacy. We randomly assigned 87 children with autism, age 13-30 months, into one of four conditions: 15 versus 25 intervention hours crossed with two different styles of intervention. We used statistical tests to examine these ideas. We found that parental efficacy was related to intervention intensity but not style. Parents with higher stress at the beginning of a 1-year, home-based, comprehensive intervention program had a higher sense of parenting efficacy if their child received lower intensity intervention; parents with lower stress at baseline had a higher sense of efficacy if their child received higher intensity intervention. If a parent can emerge from the process of diagnosis and early intervention with an increased sense that they can make a difference in their child's life (i.e. increased sense of efficacy), it may set the stage for meeting the long-term demands of parenting a child with autism.

A Multisite Randomized Controlled Trial Comparing the Effects of Intervention Intensity and Intervention Style on Outcomes for Young Children With Autism.

OBJECTIVE: This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability. METHOD: A total of 87 children with ASD, mean age 23.4 months, were assigned to 1 of 2 intervention styles (naturalistic developmental/behavioral or discrete trial teaching), each delivered for either 15 or 25 hours per week of 1:1 intervention for 12 months by trained research staff. All caregivers received coaching twice monthly. Children were assessed at 4 timepoints. Examiners and coders were naive to treatment assignment. RESULTS: Neither style nor intensity had main effects on the 4 outcome variables. In terms of moderating the effects of initial severity of developmental delay and of autism symptom severity, neither moderated the effects of treatment style on progress in any of the 4 domains. In terms of treatment intensity, initial severity moderated effect of treatment intensity on only 1 domain, namely, change in autism symptom severity; in a secondary analysis, this effect was found in only 1 site. CONCLUSION: Neither treatment style nor intensity had overall effects on child outcomes in the 4 domains examined. Initial severity did not predict better response to 1 intervention style than to another. We found very limited evidence that initial severity predicted better response to 25 vs 15 hours per week of intervention in the domains studied. CLINICAL TRIAL REGISTRATION INFORMATION: Intervention Effects of Intensity and Delivery Style for Toddlers With Autism: https://clinicaltrials.gov/; NCT02272192.

Sleep Problems and Trajectories of Restricted and Repetitive Behaviors in Children with Neurodevelopmental Disabilities.

Sleep problems are prevalent in children with neurodevelopmental disabilities and are associated with the expression of restricted and repetitive behaviors (RRBs). Children (n = 57) with autism spectrum disorder (ASD, n = 38) or developmental delay (DD, n = 19) participated in multiple assessments of intellectual ability, ASD symptoms, and RRBs (3 timepoints for ASD, 2 for DD). Sleep problems assessed at age 4 via parent report were associated with trajectories of higher-order RRBs (sameness/ritualistic/compulsive behaviors) from age 2-6 in the ASD group, and from age 2-4 in the DD group, even after controlling for intellectual ability, social-affective symptoms, and anxiety. Trajectories of stereotyped/restricted behaviors were unrelated to sleep problems. Sleep problems were associated with trajectories of higher-order (but not lower-order) RRBs in a transdiagnostic sample.

A Multisite Randomized Controlled Two-Phase Trial of the Early Start Denver Model Compared to Treatment as Usual.

OBJECTIVE: This single-blind, randomized, multisite, intent-to-treat study was designed to replicate and extend Dawson et al.'s (Pediatrics. 2010;125: e17-e23) randomized controlled trial testing the effects of the Early Start Denver Model (ESDM), an intensive play- and routines-based intervention delivered in natural settings. METHOD: A randomized controlled trial was conducted at 3 universities. One hundred eighteen children 14 to 24 months old with autism spectrum disorder were enrolled and randomly assigned to ESDM or community interventions for 27 months. Eighty-one children completed the full treatment course and all assessments; data from all 118 children were used in analyses. Children assigned to the ESDM intervention received 3 months of weekly parent coaching followed by 24 months of 15 hour per week (on average) 1:1 treatment weekly on average in homes or daycare settings from supervised therapy assistants while parents received coaching 4 hours monthly from a certified ESDM therapist. RESULTS: For the primary analyses, there were time-by-group and time-by-group-by-site interactions for language outcome. In the significant 3-way interaction involving site, 2 sites showed a significant ESDM advantage and the third site showed no significant group differences. In the planned 2-way analysis that pooled data across all 3 sites, there was a significant advantage found for the ESDM group. For the secondary analyses, there were no significant differences between the ESDM and community groups involving developmental quotient, autism severity, or adaptive behavior. The treatment effect of group on language outcomes was not moderated by baseline developmental quotient, autism severity, or language. CONCLUSION: Results of the primary analysis provide a partial replication of Dawson et al.'s 2010 language findings. CLINICAL TRIAL REGISTRATION INFORMATION: Intensive Intervention for Toddlers with Autism; https://clinicaltrials.gov/; NCT00698997.

An exploratory longitudinal study of social and language outcomes in children with autism in bilingual home environments.

Little is known about outcomes of early intervention for children with autism spectrum disorder reared in bilingual homes. There are concerns that social communication deficits among children with autism spectrum disorder may reduce the developmental benefits of early intervention for children with autism spectrum disorder raised in bilingual environments. We conducted an exploratory analysis of cross-sectional and longitudinal data from a larger study to explore associations between home language environment and language ability and social skills in response to early autism spectrum disorder intervention. Participants, aged 12-26 months when recruited, were a subset of a larger 2-year, randomized intervention trial (ClinicalTrials.gov identifier: NCT00698997). Children from bilingual homes ( n = 13) began intervention with lower gesture use but otherwise demonstrated equal baseline language and social abilities as compared with age and nonverbal IQ-matched children from monolingual homes ( n = 24). Significant language growth was exhibited by children from both language groups and there was no moderating effect of home language environment. The bilingual home group demonstrated increased gesture use over the course of intervention as compared with the monolingual home group. Preliminary data revealed no basis for concerns regarding negative impact of a bilingual home environment on language or social development in young children with autism spectrum disorder.

Altered Dynamics of the fMRI Response to Faces in Individuals with Autism.

Abnormal fMRI habituation in autism spectrum disorders (ASDs) has been proposed as a critical component in social impairment. This study investigated habituation to fearful faces and houses in ASD and whether fMRI measures of brain activity discriminate between ASD and typically developing (TD) controls. Two identical fMRI runs presenting masked fearful faces, houses, and scrambled images were collected. We found significantly slower fMRI responses to fearful faces but not houses in ASD. In addition, the pattern of slow to emerge amygdala activation to faces had robust discriminability [ASD vs. TD; area under the curve (AUC) = .852, p < .001]. In contrast, habituation to houses had no predictive value (AUC = .573, p = .365). Amygdala habituation to emotional faces may be useful for quantifying risk in ASD.

Long-Term Outcomes of Early Intervention in 6-Year-Old Children With Autism Spectrum Disorder.

OBJECTIVE: We prospectively examined evidence for the sustained effects of early intervention based on a follow-up study of 39 children with ASD who began participation in a randomized clinical trial testing the effectiveness of the Early Start Denver Model (ESDM) at age 18 to 30 months. The intervention, conducted at a high level of intensity in-home for 2 years, showed evidence of efficacy immediately posttreatment. METHOD: This group of children was assessed at age 6 years, 2 years after the intervention ended, across multiple domains of functioning by clinicians naive to previous intervention group status. RESULTS: The ESDM group, on average, maintained gains made in early intervention during the 2-year follow-up period in overall intellectual ability, adaptive behavior, symptom severity, and challenging behavior. No group differences in core autism symptoms were found immediately posttreatment; however, 2 years later, the ESDM group demonstrated improved core autism symptoms and adaptive behavior as compared with the community-intervention-as-usual (COM) group. The 2 groups were not significantly different in terms of intellectual functioning at age 6 years. Both groups received equivalent intervention hours during the original study, but the ESDM group received fewer hours during the follow-up period. CONCLUSION: These results provide evidence that gains from early intensive intervention are maintained 2 years later. Notably, core autism symptoms improved in the ESDM group over the follow-up period relative to the COM group. This improvement occurred at the same time that the ESDM group received significantly fewer services. This is the first study to examine the role of early ESDM behavioral intervention initiated at less than 30 months of age in altering the longer-term developmental course of autism.

The impact of parent-delivered intervention on parents of very young children with autism.

This study investigated the impact of a parent-coaching intervention based on the Early Start Denver Model (P-ESDM) on parenting-related stress and sense of competence. This was part of a multisite, randomized trial comparing P-ESDM (n = 49) with community intervention (n = 49) for children aged 12 and 24 months. The P-ESDM group reported no increase in parenting stress, whereas the Community group experienced an increase over the same 3-month period. Parental sense of competence did not differ. Number of negative life events was a significant predictor of parenting stress and sense of competence across both groups. This suggests that a parent-coaching intervention may help maintain parental adjustment directly after a child is diagnosed with ASD.

A novel method for assessing the development of speech motor function in toddlers with autism spectrum disorders.

There is increasing evidence to show that indicators other than socio-cognitive abilities might predict communicative function in Autism Spectrum Disorders (ASD). A potential area of research is the development of speech motor function in toddlers. Utilizing a novel measure called "articulatory features," we assess the abilities of toddlers to produce sounds at different timescales as a metric of their speech motor skills. In the current study, we examined (1) whether speech motor function differed between toddlers with ASD, developmental delay (DD), and typical development (TD); and (2) whether differences in speech motor function are correlated with standard measures of language in toddlers with ASD. Our results revealed significant differences between a subgroup of the ASD population with poor verbal skills, and the other groups, for the articulatory features associated with the shortest-timescale, namely place of articulation (POA), (p < 0.05). We also found significant correlations between articulatory features and language and motor ability as assessed by the Mullen and the Vineland scales for the ASD group. Our findings suggest that articulatory features may be an additional measure of speech motor function that could potentially be useful as an early risk indicator of ASD.

Parenting-related stress and psychological distress in mothers of toddlers with autism spectrum disorders.

BACKGROUND: Parents of children with autism spectrum disorders (ASDs) are at risk for higher stress levels than parents of children with other developmental disabilities and typical development. Recent advances in early diagnosis have resulted in younger children being diagnosed with ASDs but factors associated with parent stress in this age group are not well understood. AIMS: The present study examined parenting-related stress and psychological distress in mothers of toddlers with ASD, developmental delay without ASD (DD), and typical development. The impact of child problem behavior and daily living skills on parenting-stress and psychological distress were further investigated. METHODS: Participants were part of a larger research study on early ASD intervention. RESULTS: Parent self-report of parenting-related stress and psychological distress was utilized. Parents of toddlers with ASD demonstrated increased parenting-related stress compared with parents of toddlers with DD and typical development. However, psychological distress did not differ significantly between the groups. Child behavior problems, but not daily living skills emerged as a significant predictor of parenting-related stress and psychological distress. This was true for both mothers of children with ASD and DD. CONCLUSIONS: These finding suggest that parents' abilities to manage and reduce behavior problems is a critical target for interventions for young children with ASD and DD in order to improve child functioning and decrease parenting-related stress.

Early behavioral intervention is associated with normalized brain activity in young children with autism.

OBJECTIVE: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. METHOD: Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years. After the intervention (age 48 to 77 months), EEG activity (event-related potentials and spectral power) was measured during the presentation of faces versus objects. Age-matched typical children were also assessed. RESULTS: The ESDM group exhibited greater improvements in autism symptoms, IQ, language, and adaptive and social behaviors than the community intervention group. The ESDM group and typical children showed a shorter Nc latency and increased cortical activation (decreased α power and increased θ power) when viewing faces, whereas the community intervention group showed the opposite pattern (shorter latency event-related potential [ERP] and greater cortical activation when viewing objects). Greater cortical activation while viewing faces was associated with improved social behavior. CONCLUSIONS: This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity, which is associated with improvements in social behavior, in young children with autism spectrum disorder.

Developmental change in the ERP responses to familiar faces in toddlers with autism spectrum disorders versus typical development.

Individuals with autism spectrum disorder (ASD) show differences in face processing abilities from early in development. To examine whether these differences reflect an atypical versus delayed developmental trajectory, neural responses to familiar and unfamiliar faces in twenty-four 18- to 47-month-old children with ASD were compared with responses of thirty-two 12- to 30-month-old typically developing children. Results of 2 experiments revealed that neural responses to faces in children with ASD resembled those observed in younger typically developing children, suggesting delayed development. Electrophysiological responses to faces were also related to parent report of adaptive social behaviors for both children with ASD and typical development. Slower development of the face processing system in ASD may be related to reduced self-directed "expected" experience with faces in early development.

fMRI evidence of neural abnormalities in the subcortical face processing system in ASD.

Recent evidence suggests that a rapid, automatic face detection system is supported by subcortical structures including the amygdala, pulvinar, and superior colliculus. Early-emerging abnormalities in these structures may be related to reduced social orienting in children with autism, and subsequently, to aberrant development of cortical circuits involved in face processing. Our objective was to determine whether functional abnormalities in the subcortical face processing system are present in adults with autism spectrum disorders (ASD) during supraliminal fearful face processing. Participants included twenty-eight individuals with ASD and 25 controls group-matched on age, IQ, and behavioral performance. The ASD group met diagnostic criteria on the ADI-R, ADOS-G, and DSM-IV. Both the ASD and control groups showed significant activation in bilateral fusiform gyri. The control group exhibited additional significant responses in the right amygdala, right pulvinar, and bilateral superior colliculi. In the direct group comparison, the controls showed significantly greater activation in the left amygdala, bilateral fusiform gyrus, right pulvinar, and bilateral superior colliculi. No brain region showed significantly greater activation in the ASD group compared to the controls. Thus, basic rapid face identification mechanisms appear to be functional in ASD. However, individuals with ASD failed to engage the subcortical brain regions involved in face detection and automatic emotional face processing, suggesting a core mechanism for impaired socioemotional processing in ASD. Neural abnormalities in this system may contribute to early-emerging deficits in social orienting and attention, the putative precursors to abnormalities in social cognition and cortical face processing specialization.

Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders.

Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD.

Response to familiar faces, newly familiar faces, and novel faces as assessed by ERPs is intact in adults with autism spectrum disorders.

Individuals with autism spectrum disorders (ASD) have pervasive impairments in social functioning, which may include problems with processing and remembering faces. In this study, we examined whether posterior ERP components associated with identity processing (P2, N250 and face-N400) and components associated with early-stage face processing (P1 and N170) are atypical in ASD. We collected ERP responses to a familiar repeated face (Familiar), an unfamiliar repeated face (Other) and novel faces (Novels) in 29 high-functioning adults with ASD and matched controls. For both groups, the P2 and N250 were sensitive to repetition (Other vs. Novels) and personal familiarity (Familiar vs. Other), and the face-N400 was sensitive to repetition. Adults with ASD did not show significantly atypical processing of facial familiarity and repetition in an ERP paradigm, despite showing significantly poorer performance than controls on a behavioral test of face memory. This study found no evidence that early-stage facial identity processing is a primary contributor to the face recognition deficit in high-functioning ASD.

Toddlers with elevated autism symptoms show slowed habituation to faces.

We explored social information processing and its relation to social and communicative symptoms in toddlers with Autism Spectrum Disorder (ASD) and their siblings. Toddlers with more severe symptoms of autism showed slower habituation to faces than comparison groups; slower face learning correlated with poorer social skills and lower verbal ability. Unaffected toddlers who were siblings of children with ASD also showed slower habituation to faces compared with toddlers without siblings with ASD. We conclude that slower rates of face learning may be an endophenotype of ASD and is associated with more severe symptoms among affected individuals.

Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model.

OBJECTIVE: To conduct a randomized, controlled trial to evaluate the efficacy of the Early Start Denver Model (ESDM), a comprehensive developmental behavioral intervention, for improving outcomes of toddlers diagnosed with autism spectrum disorder (ASD). METHODS: Forty-eight children diagnosed with ASD between 18 and 30 months of age were randomly assigned to 1 of 2 groups: (1) ESDM intervention, which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years; or (2) referral to community providers for intervention commonly available in the community. RESULTS: Compared with children who received community-intervention, children who received ESDM showed significant improvements in IQ, adaptive behavior, and autism diagnosis. Two years after entering intervention, the ESDM group on average improved 17.6 standard score points (1 SD: 15 points) compared with 7.0 points in the comparison group relative to baseline scores. The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children. In contrast, over the 2-year span, the comparison group showed greater delays in adaptive behavior. Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder, not otherwise specified, than the comparison group. CONCLUSIONS: This is the first randomized, controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis. Results of this study underscore the importance of early detection of and intervention in autism.

Reduced neural habituation in the amygdala and social impairments in autism spectrum disorders.

OBJECTIVE: Amygdala dysfunction has been proposed as a critical component in social impairment in autism spectrum disorders. This study was designed to investigate whether abnormal habituation characterizes amygdala dysfunction in autism spectrum disorders and whether the rate of amygdala habituation is related to social impairment. METHOD: Using functional MRI, the authors measured change over time in activation of the amygdala and fusiform gyrus to neutral facial stimuli in adults with autism spectrum disorders and healthy comparison adults. RESULTS: The comparison group evidenced significantly greater amygdala habituation bilaterally than the autism spectrum group. There were no group differences in overall fusiform habituation. For the autism spectrum group, lower levels of habituation of the amygdala to the face stimuli were associated with more severe social impairment. CONCLUSIONS: These results suggest amygdala hyperarousal in autism spectrum disorders in response to socially relevant stimuli. Further, sustained amygdala arousal may contribute to the social deficits observed in autism spectrum disorders.

Abnormal functional connectivity in autism spectrum disorders during face processing.

Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning adults with ASD and 21 age-and IQ-matched control adults. Activation during identification of previously viewed faces and houses using a one-back paradigm was compared. The fusiform face area (FFA) was individually localized in each participant and used as the seed point for functional connectivity analyses. The degree of correlation between FFA and the extended neural circuitry involved in face identification was tested. A whole brain analysis was also conducted in order to determine whether connectivity from the FFA to aberrant brain locations was present in the ASD group. Measures of clinical severity (ADOS social score and ADI-R social score) were included as independent variables into the functional connectivity analyses. Significant FFA-amygdala and FFA-superior temporal sulcus functional connectivity was found in both the ASD and control participants. However, the control group had significantly increased connectivity to the left amygdala and the posterior cingulate compared to ASD. Post hoc analyses additionally found increased connectivity to the thalamus in the controls. A significant relationship between abnormal functional connectivity and clinical severity in the ASD group was observed. Specifically, greater social impairment was associated with reduced FFA-amygdala connectivity and increased FFA-right inferior frontal connectivity. These results suggest that abnormal neural connections within the limbic system may contribute to the social impairments observed in ASD.