White matter development and language abilities during infancy in autism spectrum disorder.

White matter (WM) fiber tract differences are present in autism spectrum disorder (ASD) and could be important markers of behavior. One of the earliest phenotypic differences in ASD are language atypicalities. Although language has been linked to WM in typical development, no work has evaluated this association in early ASD. Participants came from the Infant Brain Imaging Study and included 321 infant siblings of children with ASD at high likelihood (HL) for developing ASD; 70 HL infants were later diagnosed with ASD (HL-ASD), and 251 HL infants were not diagnosed with ASD (HL-Neg). A control sample of 140 low likelihood infants not diagnosed with ASD (LL-Neg) were also included. Infants contributed expressive language, receptive language, and diffusion tensor imaging data at 6-, 12-, and 24 months. Mixed effects regression models were conducted to evaluate associations between WM and language trajectories. Trajectories of microstructural changes in the right arcuate fasciculus were associated with expressive language development. HL-ASD infants demonstrated a different developmental pattern compared to the HL-Neg and LL-Neg groups, wherein the HL-ASD group exhibited a positive association between WM fractional anisotropy and language whereas HL-Neg and LL-Neg groups showed weak or no association. No other fiber tracts demonstrated significant associations with language. In conclusion, results indicated arcuate fasciculus WM is linked to language in early toddlerhood for autistic toddlers, with the strongest associations emerging around 24 months. To our knowledge, this is the first study to evaluate associations between language and WM development during the pre-symptomatic period in ASD.

Brief Report: The Broad Autism Phenotype in Swedish Parents of Children With and Without Autism Spectrum Conditions.

The broad autism phenotype (BAP) is a set of characteristics often observed in typically developing people with a genetic load for autism, such as parents of autistic children. The Broad Autism Phenotypic Questionnaire (BAPQ) is a 36-item questionnaire developed to identify the BAP in first-degree relatives of autistic people. We translated the BAPQ into Swedish and examined its psychometric properties in a Swedish sample consisting of 45 parents of children with ASC and 74 parents of non-autistic children. We found support for the original 3-factor structure (aloof, pragmatic language and rigid), good internal consistency and convergent validity with the Autism Quotient. Thus, the Swedish BAPQ exhibits acceptable psychometric properties and may be useful for assessing the BAP in non-clinical populations.

Diagnostic shifts in autism spectrum disorder can be linked to the fuzzy nature of the diagnostic boundary: a data-driven approach.

BACKGROUND: Diagnostic shifts at early ages may provide invaluable insights into the nature of separation between autism spectrum disorder (ASD) and typical development. Recent conceptualizations of ASD suggest the condition is only fuzzily separated from non-ASD, with intermediate cases between the two. These intermediate cases may shift along a transition region over time, leading to apparent instability of diagnosis. METHODS: We used a cohort of children with high ASD risk, by virtue of having an older sibling with ASD, assessed at 24 months (N = 212) and 36 months (N = 191). We applied machine learning to empirically characterize the classification boundary between ASD and non-ASD, using variables quantifying developmental and adaptive skills. We computed the distance of children to the classification boundary. RESULTS: Children who switched diagnostic labels from 24 to 36 months, in both directions, (dynamic group) had intermediate phenotypic profiles. They were closer to the classification boundary compared to children who had stable diagnoses, both at 24 months (Cohen's d = .52) and at 36 months (d = .75). The magnitude of change in distance between the two time points was similar for the dynamic and stable groups (Cohen's d = .06), and diagnostic shifts were not associated with a large change. At the individual level, a few children in the dynamic group showed substantial change. CONCLUSIONS: Our results suggested that a diagnostic shift was largely due to a slight movement within a transition region between ASD and non-ASD. This fact highlights the need for more vigilant surveillance and intervention strategies. Young children with intermediate phenotypes may have an increased susceptibility to gain or lose their diagnosis at later ages, calling attention to the inherently dynamic nature of early ASD diagnoses.

Towards a Data-Driven Approach to Screen for Autism Risk at 12 Months of Age.

OBJECTIVE: This study aimed to develop a classifier for infants at 12 months of age based on a parent-report measure (the First Year Inventory 2.0 [FYI]), for the following reasons: (1) to classify infants at elevated risk, above and beyond that attributable to familial risk status for ASD; and (2) to serve as a starting point to refine an approach for risk estimation in population samples. METHOD: A total of 54 high-familial risk (HR) infants later diagnosed with ASD (HR-ASD), 183 HR infants not diagnosed with ASD at 24 months of age (HR-Neg), and 72 low-risk controls participated in the study. All infants contributed FYI data at 12 months of age and had a diagnostic assessment for ASD at age 24 months. A data-driven, cross-validated analytic approach was used to develop a classifier to determine screening accuracy (eg, sensitivity) of the FYI to classify HR-ASD and HR-Neg. RESULTS: The newly developed FYI classifier had an estimated sensitivity of 0.71 (95% CI: 0.50, 0.91) and specificity of 0.72 (95% CI: 0.49, 0.91). CONCLUSION: This classifier demonstrates the potential to improve current screening for ASD risk at 12 months of age in infants already at elevated familial risk for ASD, increasing opportunities for detection of autism risk in infancy. Findings from this study highlight the utility of combining parent-report measures with machine learning approaches.

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.

Early language exposure supports later language skills in infants with and without autism.

The way that parents communicate with their typically developing infants is associated with later infant language development. Here we aim to show that these associations are observed in infants subsequently diagnosed with autism spectrum disorder (ASD). This study had three groups: high-familial-risk infants who did not have ASD (n = 46); high-familial-risk infants who had ASD (n = 14); and low-familial-risk infants who exhibited typical development (n = 36). All-day home language recordings were collected at 9 and 15 months, and language skills were assessed at 24 months. Across all infants in the study, including those with ASD, a richer home language environment (e.g., hearing more adult words and experiencing more conversational turns) at 9 and 15 months was associated with better language skills. Higher parental educational attainment was associated with a richer home language environment. Mediation analyses showed that the effect of education on child language skills was explained by the richness of the home language environment. Exploratory analyses revealed that typically developing infants experience an increase in caregiver-child conversational turns across 9-15 months, a pattern not seen in children with ASD. The current study shows that parent behavior during the earliest stages of life can have a significant impact on later development, highlighting the home language environment as means to support development in infants with ASD. Autism Res 2019, 12: 1784-1795. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: It has long been understood that caregiver speech supports language skills in typically developing infants. In this study, parents of infants who were later diagnosed with ASD and parents of infants in the control groups completed all-day home language recordings. We found that for all infants in our study, those who heard more caregiver speech had better language skills later in life. Parental education level was also related to how much caregiver speech an infant experienced.