Quantifying latent social motivation and its associations with joint attention and language in infants at high and low likelihood for autism spectrum disorder.

Social motivation-the psychobiological predisposition for social orienting, seeking social contact, and maintaining social interaction-manifests in early infancy and is hypothesized to be foundational for social communication development in typical and atypical populations. However, the lack of infant social-motivation measures has hindered delineation of associations between infant social motivation, other early-arising social abilities such as joint attention, and language outcomes. To investigate how infant social motivation contributes to joint attention and language, this study utilizes a mixed longitudinal sample of 741 infants at high (HL = 515) and low (LL = 226) likelihood for ASD. Using moderated nonlinear factor analysis (MNLFA), we incorporated items from parent-report measures to establish a novel latent factor model of infant social motivation that exhibits measurement invariance by age, sex, and familial ASD likelihood. We then examined developmental associations between 6- and 12-month social motivation, joint attention at 12-15 months, and language at 24 months of age. On average, greater social-motivation growth from 6-12 months was associated with greater initiating joint attention (IJA) and trend-level increases in sophistication of responding to joint attention (RJA). IJA and RJA were both positively associated with 24-month language abilities. There were no additional associations between social motivation and future language in our path model. These findings substantiate a novel, theoretically driven approach to modeling social motivation and suggest a developmental cascade through which social motivation impacts other foundational skills. These findings have implications for the timing and nature of intervention targets to support social communication development in infancy. HIGHLIGHTS: We describe a novel, theoretically based model of infant social motivation wherein multiple parent-reported indicators contribute to a unitary latent social-motivation factor. Analyses revealed social-motivation factor scores exhibited measurement invariance for a longitudinal sample of infants at high and low familial ASD likelihood. Social-motivation growth from ages 6-12 months is associated with better 12-15-month joint attention abilities, which in turn are associated with greater 24-month language skills. Findings inform timing and targets of potential interventions to support healthy social communication in the first year of life.

Toddlers at Elevated Likelihood for Autism: Exploring Sensory and Language Treatment Predictors.

Baseline child characteristics may predict treatment outcomes in children with or at elevated likelihood of developing autism (EL-ASD). Little is known about the role of child sensory and language features on treatment outcome. Participants were randomly assigned to a parent-mediated intervention or control condition. Analyses explored the relationship between baseline child sensory and language characteristics and changes in ASD symptoms over approximately 9 months. Higher baseline sensory hyporeactivity was significantly related to less improvement in social communication (SC) for the treatment group only. More baseline atypical vocalizations were significantly related to less improvement on SC across treatment and control groups. This work provides an initial framework to encourage the tailoring of interventions for EL-ASD children, suggesting sensory reactivity and atypical vocalizations may be useful behaviors to consider in treatment planning.

Risk factors and clinical correlates of sensory dysfunction in preschool children with and without autism spectrum disorder.

Sensory dysfunction is a common feature of autism spectrum disorder (ASD). The objectives of this analysis were to examine risk factors and clinical correlates of sensory dysfunction in preschool children with and without ASD. Children aged 2-5 years were enrolled in a multi-site case-control study. Data were collected in eight areas across the United States in three phases. Caregivers completed an interview with questions on assisted delivery, maternal alcohol use, maternal anxiety during pregnancy, pregnancy weight gain, neonatal jaundice, preterm birth, and child sensory diagnosis given by a healthcare provider. Caregivers also completed an interview and questionnaires on sensory symptoms and clinical correlates of sensory dysfunction in their child. There were 2059 children classified as ASD, 3139 as other developmental delay or disability (DD), and 3249 as population comparison (POP). Caregivers reported significantly more sensory diagnoses and sensory symptoms in children classified as ASD than DD or POP (23.7%, 8.6%, and 0.8%, respectively, for a sensory diagnosis and up to 78.7% [ASD] vs. 49.6% [DD] for sensory symptoms). Maternal anxiety during pregnancy and neonatal jaundice were significantly associated with a sensory diagnosis and certain sensory symptoms in children with ASD and DD. Children's anxiety, attention deficits/hyperactivity, and sleep problems were significantly albeit subtly correlated with both a sensory diagnosis and sensory symptoms in children with ASD and DD. These findings support sensory dysfunction as a distinguishing symptom of ASD in preschool children and identify risk factors and clinical correlates to inform screening and treatment efforts in those with atypical development.

Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome.

BACKGROUND: Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants. METHODS: The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls. RESULTS: Infants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD. CONCLUSIONS: Our results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.

Sex Differences in the Developmental Trajectories of Autism Spectrum Disorder.

Purpose of Review: Females and males are disproportionately diagnosed with autism, a sex difference that has historically represented this neurodevelopmental condition. The current review examines lifespan developmental trajectories of autism based on sex to elucidate behavioral phenotypic differences that may contribute to differential rates of diagnosis. Recent Findings: We review sex differences in diagnostic criteria: social communication and restricted interests/repetitive behaviors (RRBs). Results suggest RRBs are more indicative of a diagnosis in males, whereas social differences are more indicative of a diagnosis in females. Factors contributing to a later diagnosis in females include social strengths (camouflaging) and diagnostic overshadowing. Summary: Sex differences in diagnostic criteria may contribute to differential rates of identification in males and females. Sex differences are most pronounced when assessing naturalistic social communication instead of reliance on standardized measure. Numerous future directions are identified including increasing samples of sub-threshold autistic females and evaluating longitudinal sex differences.

Examining Treatment Outcomes Across Contexts: How Do Child Baseline Characteristics Impact Measurement of Treatment Response?

The evaluation of the overlap between the ADOS BOSCC and Standard BOSCC as well as the exploration of child characteristics that may predict change are important steps in consolidating data-driven definitions of "improvement". Participants were seen between 2 and 5 times with Standard BOSCC and ADOS BOSCC observations over the course of early intervention trials (Grzadzinski et al. in J Autism Dev Disord 46:2464, 2016; Kim et al. in Autism 23:5, 2019). Results showed consistency between the Standard BOSCC and ADOS BOSCC, highlighting the utility of both as metrics of change and treatment outcome across contexts. Baseline characteristics may play a role in the tailoring of early intervention to maximize treatment outcome and may offer guidance when determining which outcome measures to use.

Sensory Profiles in Relation to Later Adaptive Functioning Among Toddlers at High-Familial Likelihood for Autism.

This study investigated the extent to which sensory responsivity in infancy contributes to adaptive behavior development among toddlers at high-familial likelihood for autism. Prospective, longitudinal data were analyzed for 218 children, 58 of whom received an autism diagnosis. Results indicated that sensory profiles at age one year (hyperresponsivity, sensory seeking) were negatively associated with later adaptive behavior, particularly for socialization, at age 3 years regardless of diagnostic status. These results suggest that early differences in sensory responsivity may have downstream developmental consequences related to social development among young children with high-familial likelihood for autism.

Association of Sex With Neurobehavioral Markers of Executive Function in 2-Year-Olds at High and Low Likelihood of Autism.

Importance: Children with autism and their siblings exhibit executive function (EF) deficits early in development, but associations between EF and biological sex or early brain alterations in this population are largely unexplored. Objective: To investigate the interaction of sex, autism likelihood group, and structural magnetic resonance imaging alterations on EF in 2-year-old children at high familial likelihood (HL) and low familial likelihood (LL) of autism, based on having an older sibling with autism or no family history of autism in first-degree relatives. Design, Setting, and Participants: This prospective cohort study assessed 165 toddlers at HL (n = 110) and LL (n = 55) of autism at 4 university-based research centers. Data were collected from January 1, 2007, to December 31, 2013, and analyzed between August 2021 and June 2022 as part of the Infant Brain Imaging Study. Main Outcomes and Measures: Direct assessments of EF and acquired structural magnetic resonance imaging were performed to determine frontal lobe, parietal lobe, and total cerebral brain volume. Results: A total of 165 toddlers (mean [SD] age, 24.61 [0.95] months; 90 [54%] male, 137 [83%] White) at HL for autism (n = 110; 17 diagnosed with ASD) and LL for autism (n = 55) were studied. The toddlers at HL for autism scored lower than the toddlers at LL for autism on EF tests regardless of sex (mean [SE] B = -8.77 [4.21]; 95% CI, -17.09 to -0.45; η2p = 0.03). With the exclusion of toddlers with autism, no group (HL vs LL) difference in EF was found in boys (mean [SE] difference, -7.18 [4.26]; 95% CI, 1.24-15.59), but EF was lower in HL girls than LL girls (mean [SE] difference, -9.75 [4.34]; 95% CI, -18.32 to -1.18). Brain-behavior associations were examined, controlling for overall cerebral volume and developmental level. Sex differences in EF-frontal (B [SE] = 16.51 [7.43]; 95% CI, 1.36-31.67; η2p = 0.14) and EF-parietal (B [SE] = 17.68 [6.99]; 95% CI, 3.43-31.94; η2p = 0.17) associations were found in the LL group but not the HL group (EF-frontal: B [SE] = -1.36 [3.87]; 95% CI, -9.07 to 6.35; η2p = 0.00; EF-parietal: B [SE] = -2.81 [4.09]; 95% CI, -10.96 to 5.34; η2p = 0.01). Autism likelihood group differences in EF-frontal (B [SE] = -9.93 [4.88]; 95% CI, -19.73 to -0.12; η2p = 0.08) and EF-parietal (B [SE] = -15.44 [5.18]; 95% CI, -25.86 to -5.02; η2p = 0.16) associations were found in girls not boys (EF-frontal: B [SE] = 6.51 [5.88]; 95% CI, -5.26 to 18.27; η2p = 0.02; EF-parietal: B [SE] = 4.18 [5.48]; 95% CI, -6.78 to 15.15; η2p = 0.01). Conclusions and Relevance: This cohort study of toddlers at HL and LL of autism suggests that there is an association between sex and EF and that brain-behavior associations in EF may be altered in children at HL of autism. Furthermore, EF deficits may aggregate in families, particularly in girls.

Caregiver responsiveness as a mechanism to improve social communication in toddlers: Secondary analysis of a randomized controlled trial.

Early intensive behavioral interventions (EIBI) for children at elevated likelihood for a later diagnosis of autism spectrum disorder (EL-ASD), are often delivered through parent-mediated models. An area of current exploration is whether changes in caregiver behaviors are a mechanism through which to improve and track child behaviors in these interventions. Toddlers and their caregivers participated in an intervention trial (randomized controlled trial) and were randomized to either a parent-mediated intervention (adapted responsive teaching; ART) or a control condition (referral to early intervention and monitoring; REIM). Changes in toddler social communication (SC) behaviors and characteristics of caregiver responsiveness (CR) were quantified over 8 months. Analyses were conducted to assess whether changes in CR mediated the relation between group (ART vs. REIM) and changes in child SC. Results of the current study indicated that caregivers who participated in a parent-mediated intervention improved in three domains of CR (contingent verbal sensitivity, responsivity, affect). CR was also found to be a mechanism through which children's SC skills improved. This work provides evidence that qualities of CR serve as mechanisms through which to improve and monitor child behaviors over the course of EIBIs. These results may lead to novel intervention targets, methods for tracking change, and tailored treatment planning for toddlers with EL-ASD. The data used in this study comes from a clinical trial that was prospectively registered with the Registry of Efficacy and Effectiveness Studies (Registry ID: 316.1v1). LAY SUMMARY: Interventions for toddlers with high likelihood for a later diagnosis of autism often include the caregiver as an active participant in the intervention. In this study, we aimed to understand qualities of caregiver responsiveness (CR) that facilitate improvements in child behaviors during intervention. Results show that increasing verbal CR and affect are ways to improve child social skills over the course of intervention.

Extending the Usefulness of the Brief Observation of Social Communication Change (BOSCC): Validating the Phrase Speech and Young Fluent Version.

The current study investigated the utility of the Brief Observation of Social Communication Change-Phrase Speech Young Fluent (BOSCC-PSYF) as an outcome measure of treatment response by analyzing the measure's psychometric properties and initial validity. The BOSCC coding scheme was applied to 345 administrations from 160 participants diagnosed with autism. Participants included individuals of any age with phrase speech, or individuals under the age of 8 years with complex sentences. All were receiving behavioral intervention throughout the study. Test-retest and inter-rater reliability were good for the Early Communication and Social Reciprocity/Language domains, and fair for the Restricted and Repetitive Behavior domain. Significant changes occurred over time in the Early Communication and Social Reciprocity/Language domains, and Core Total scores. The BOSCC-PSYF may provide a low-cost, flexible, and user-friendly outcome measure that reliably measures changes in broad social communicative behaviors in a short period of time.

A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder-Associated Impairment in Early Childhood.

BACKGROUND: Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD. METHODS: We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total nobservations = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; nobservations = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership. RESULTS: We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group. CONCLUSIONS: This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence.

Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy.

Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.

Parent responsiveness mediates the association between hyporeactivity at age 1 year and communication at age 2 years in children at elevated likelihood of ASD.

Studies suggest that higher parent responsiveness is associated with higher child language abilities. Infants and toddlers later diagnosed with autism spectrum disorder (ASD) often display hyporeactivity to sensory stimuli, which has also been associated with lower child communication abilities and lower parent responsiveness. Yet, whether parent responsiveness mediates the relationship between child hyporeactivity and later communication outcomes remains unexplored. This study is a secondary data analysis which includes children (n = 83; 56 males) identified as at elevated likelihood of later ASD. Children completed an observational measure of sensory reactivity and a standard developmental assessment at 14 (Time 1) and 23 months old (Time 2). At each time point, parents reported on the child's adaptive communication behaviors and sensory behaviors, and Parent Verbal Responsiveness (AvgPVR) was coded from parent-child free-play videos. Results indicated that the association between child sensory hyporeactivity at Time 1 (observed and parent-reported) and communication at Time 2 (observed and parent reported) was significantly mediated by AvgPVR. Although child hyporeactivity predicts poorer communication outcomes, increased parent verbal responsiveness may attenuate this negative impact. Parent responsiveness, a focus of many parent-mediated interventions, may be an important mechanism of treatment response that should be directly tested in future research. LAY SUMMARY: Toddlers at elevated likelihood of autism spectrum disorder (ASD) are often under-reactive (hyporeactive) to sensory stimuli. This hyporeactivity slows learning of communication skills and provides parents with fewer opportunities to respond to their children. In this study, children with hyporeactivity at 14 months generally had poorer communication at 23 months; however, the more responsive their parents were, the weaker the relationship between early hyporeactivity and later communication. Thus, increasing parent responsiveness may lead to better communication outcomes for toddlers with the early ASD symptom of hyporeactivity.

Pre-symptomatic intervention for autism spectrum disorder (ASD): defining a research agenda.

Autism spectrum disorder (ASD) impacts an individual's ability to socialize, communicate, and interact with, and adapt to, the environment. Over the last two decades, research has focused on early identification of ASD with significant progress being made in understanding the early behavioral and biological markers that precede a diagnosis, providing a catalyst for pre-symptomatic identification and intervention. Evidence from preclinical trials suggest that intervention prior to the onset of ASD symptoms may yield more improved developmental outcomes, and clinical studies suggest that the earlier intervention is administered, the better the outcomes. This article brings together a multidisciplinary group of experts to develop a conceptual framework for behavioral intervention, during the pre-symptomatic period prior to the consolidation of symptoms into diagnosis, in infants at very-high-likelihood for developing ASD (VHL-ASD). The overarching goals of this paper are to promote the development of new intervention approaches, empirical research, and policy efforts aimed at VHL-ASD infants during the pre-symptomatic period (i.e., prior to the consolidation of the defining features of ASD).

Social and non-social sensory responsivity in toddlers at high-risk for autism spectrum disorder.

Empirical evidence concerning sensory responsivity in young children who later develop autism spectrum disorder (ASD) remains relatively limited. It is unclear whether specific patterns or aspects of sensory responsivity underlay the emergence of the disorder. The goals of this study were to (a) examine whether social versus non-social context impacted the expression of sensory responsivity in infants at high risk for ASD, and (b) examine if sensory responsivity in social or non-social contexts was associated with severity of ASD symptoms. The Sensory Experiences Questionnaire 2.1 was collected for 338 infants (131 females, 207 males) at high-risk for ASD at 12 and/or 24 months of age. High-risk toddlers meeting diagnostic criteria for ASD (n = 75) showed elevated sensory responsivity in both social and non-social contexts at 12 months of age and differences widened over the second year of life. Individuals with ASD demonstrate higher responsivity in both contexts suggestive of generalized atypical sensory responsivity in ASD. LAY SUMMARY: Behaviors such as avoiding or noticing sensory input (e.g., sounds, touches) are often different in individuals with autism spectrum disorder (ASD) than those without. The reason for this is widely unknown. The findings from this study show that in toddlers, sensory responsivity increased in both social and non-social situations. Therefore, the setting of sensory input does not explain these differences.

Longitudinal Prediction of Infant MR Images With Multi-Contrast Perceptual Adversarial Learning.

The infant brain undergoes a remarkable period of neural development that is crucial for the development of cognitive and behavioral capacities (Hasegawa et al., 2018). Longitudinal magnetic resonance imaging (MRI) is able to characterize the developmental trajectories and is critical in neuroimaging studies of early brain development. However, missing data at different time points is an unavoidable occurrence in longitudinal studies owing to participant attrition and scan failure. Compared to dropping incomplete data, data imputation is considered a better solution to address such missing data in order to preserve all available samples. In this paper, we adapt generative adversarial networks (GAN) to a new application: longitudinal image prediction of structural MRI in the first year of life. In contrast to existing medical image-to-image translation applications of GANs, where inputs and outputs share a very close anatomical structure, our task is more challenging as brain size, shape and tissue contrast vary significantly between the input data and the predicted data. Several improvements over existing GAN approaches are proposed to address these challenges in our task. To enhance the realism, crispness, and accuracy of the predicted images, we incorporate both a traditional voxel-wise reconstruction loss as well as a perceptual loss term into the adversarial learning scheme. As the differing contrast changes in T1w and T2w MR images in the first year of life, we incorporate multi-contrast images leading to our proposed 3D multi-contrast perceptual adversarial network (MPGAN). Extensive evaluations are performed to assess the qualityand fidelity of the predicted images, including qualitative and quantitative assessments of the image appearance, as well as quantitative assessment on two segmentation tasks. Our experimental results show that our MPGAN is an effective solution for longitudinal MR image data imputation in the infant brain. We further apply our predicted/imputed images to two practical tasks, a regression task and a classification task, in order to highlight the enhanced task-related performance following image imputation. The results show that the model performance in both tasks is improved by including the additional imputed data, demonstrating the usability of the predicted images generated from our approach.

Recent Developments in Treatment Outcome Measures for Young Children With Autism Spectrum Disorder (ASD).

Significant advancements have been made in early intervention programs for children with Autism spectrum disorder (ASD). However, measuring treatment response for children with ASD is difficult due to the heterogeneity of changes in symptoms, which can be subtle, especially over a short period of time. Here we outline the challenge of evaluating treatment response with currently available measures as well as newly developed or refined measures that may be useful in clinical trials for young children with ASD. Continued development of treatment outcome measures will help the field identify and compare efficacious interventions and tailor treatments for children with ASD.

Sensory Reactivity at 1 and 2 Years Old is Associated with ASD Severity During the Preschool Years.

Children with Autism Spectrum Disorder (ASD) often display atypical sensory reactivity within the first years of life, prior to a diagnosis. This study examined sensory reactivity patterns at 14 months, changes from 14 to 23 months, and later ASD severity at 3 to 5 years of age in children (n = 87) at elevated likelihood of ASD. Results indicated that observed hyporeactivity at 14 months and increases from 14 to 23 months were related to higher ASD severity during the preschool years. Parent report of hyperreactivity at 14 months was associated with higher ASD severity in the RRB domain during the preschool years. Early hypo and hyperreactivity may predict later severity of ASD and aid in subtyping and developing individualized treatments.

Quantitative trait variation in ASD probands and toddler sibling outcomes at 24 months.

BACKGROUND: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings. METHODS: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings were assessed using the ADI-R, VABS-II, Mullen Scales of Early Learning (MSEL), and Autism Diagnostic Observation Schedule (ADOS) and received a clinical best estimate diagnosis at 24 months using DSM-IV-TR criteria (n = 89 concordant for ASD; n = 296 discordant). We addressed two aims: (1) to determine whether proband characteristics are predictive of recurrence in siblings and (2) to assess associations between proband traits and sibling dimensional outcomes at 24 months. RESULTS: Regarding recurrence risk, proband SCQ scores were found to significantly predict sibling 24-month diagnostic outcome (OR for a 1-point increase in SCQ = 1.06; 95% CI = 1.01, 1.12). Regarding quantitative trait associations, we found no significant correlations in ASD traits among proband-sibling pairs. However, quantitative variation in proband adaptive behavior, communication, and expressive and receptive language was significantly associated with sibling outcomes in the same domains; proband scores explained 9-18% of the variation in cognition and behavior in siblings with ASD. Receptive language was particularly strongly associated in concordant pairs (ICC = 0.50, p < 0.001). CONCLUSIONS: Proband ASD symptomology, indexed by the SCQ, is a predictor of familial ASD recurrence risk. While quantitative variation in social communication and restricted and repetitive behavior were not associated among sibling pairs, standardized ratings of proband language and communication explained significant variation in the same domains in the sibling at 24 months, especially among toddlers with an ASD diagnosis. These data suggest that proband characteristics can alert clinicians to areas of developmental concern for young children with familial risk for ASD.

Measuring treatment response in children with autism spectrum disorder: Applications of the Brief Observation of Social Communication Change to the Autism Diagnostic Observation Schedule.

This study aims to determine the validity and reliability of applying the coding strategy from the Brief Observation of Social Communication Change, a newly validated treatment outcome measure, to videotaped segments of the Autism Diagnostic Observation Schedule. Results indicate strong reliability and validity of the Brief Observation of Social Communication Change ratings using the Autism Diagnostic Observation Schedule segments in detecting changes in social communication over the course of treatment in young, minimally verbal children with autism spectrum disorder. Results also suggest that the Brief Observation of Social Communication Change, when applied to Autism Diagnostic Observation Schedule segments, may be more sensitive in detecting subtle changes in social communication compared to the Autism Diagnostic Observation Schedule Calibrated Severity Scores. These results may support the application of the Brief Observation of Social Communication Change to pre-existing datasets of Autism Diagnostic Observation Schedule videos to examine treatment responses.