Characteristics of the broader phenotype in autism: a study of siblings using the children's communication checklist-2.
ABSTRACT Non-autistic relatives of people with autistic disorder have an increased risk of social and communicative difficulties: this is known as the "broad phenotype." Better methods for characterizing the broad phenotype are needed to facilitate identification of risk genes for autism. 29 siblings of 20 children with autistic disorder, 13 siblings of 9 children with PDDNOS, and 46 typically developing control children from 26 families were assessed by parental report using the Children's Communication Checklist-2 (CCC-2). Groups were matched on age and IQ and siblings with autism were excluded. Group mean scores on the CCC-2 differed on only one subscale, syntax. However, siblings of children with autism or PDDNOS were over-represented in the tails of the distributions of several scales, and 10 (24%) scored more than 2 SD below the control mean on a total score based on all 10 subscales. Only two of these 10 children scored above threshold on one or more scales of the Autism Diagnostic Interview-Revised (ADI-R). Children with abnormal scores on the CCC-2 total were characterized by low-verbal IQ and their fathers tended to score high on the social and communication scales of the Autism Quotient, a measure of the broad phenotype in adults. The CCC-2 shows promise as a quick screening device for the broad phenotype in non-autistic siblings of children with autism.
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ABSTRACT: This paper examined early developmental trajectories in a large, longitudinal sample at high-risk for ASD (‘HR’) and low-risk (‘LR’) controls, and the association of trajectories with 3-year diagnosis. Developmental assessments were conducted at 6, 12, 24 months, and 3 years, with blinded “clinical best-estimate” expert diagnosis at age 3. HR infants were enrolled based only on familial risk. LR infants, from community sources, had no first- or second-degree ASD relatives. All infants were born at 36–42 weeks, weighing ≥2500 g, with no identifiable neurological, genetic, or severe sensory/motor disorders. Analytic phase I: semi-parametric group-based modeling to identify distinct developmental trajectories (n = 680; 487 HR; 193 LR); phase II: Trajectory membership in relation to 3-year diagnosis (n = 424; 310 HR; 114 LR). Three distinct trajectories emerged (1) inclining; (2) stable-average; (3) declining; trajectory membership predicted diagnosis (χ2 = 99.40; p < .001). Most ASD cases were in stable-average (50.6%) or declining trajectories (33.8%); most non-ASD-HR infants were in inclining (51.9%) or stable-average (40.3%) trajectories. The majority of LR controls were in the inclining trajectory (78.9%). Within the declining trajectory, over half had ASD (57.8%), but 40% were non-ASD-HR infants. Declining/plateauing raw scores were associated with, but not exclusive to, ASD. Findings underscore the importance of monitoring the emergence of ASD symptoms and overall development in high-risk children. Evidence of developmental slowing or decline may be associated not only with ASD, but with other suboptimal outcomes, warranting careful clinical follow-up.Research in Autism Spectrum Disorders 11/2014; 8(11):1557–1566. · 2.96 Impact Factor
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ABSTRACT: The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD.Proceedings of the National Academy of Sciences 08/2014; · 9.81 Impact Factor
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ABSTRACT: Background We evaluated early pragmatic language skills in preschool-age siblings of children with autism spectrum disorder (ASD), and examined correspondence between pragmatic language impairments and general language difficulties, autism symptomatology, and clinical outcomes.Methods Participants were younger siblings of children with ASD (high-risk, n = 188) or typical development (low-risk, n = 119) who were part of a prospective study of infants at risk for ASD; siblings without ASD outcomes were included in analyses. Pragmatic language skills were measured via the Language Use Inventory (LUI).ResultsAt 36 months, the high-risk group had significantly lower parent-rated pragmatic language scores than the low-risk group. When defining pragmatic language impairment (PLI) as scores below the 10th percentile on the LUI, 35% of the high-risk group was identified with PLI versus 10% of the low-risk group. Children with PLI had higher rates of general language impairment (16%), defined as scores below the 10th percentile on the Receptive or Expressive Language subscales of the Mullen Scales of Early Learning, relative to those without PLI (3%), but most did not evidence general language impairments. Children with PLI had significantly higher ADOS scores than those without PLI and had higher rates of clinician-rated atypical clinical best estimate outcomes (49%) relative to those without PLI (15%).Conclusions Pragmatic language problems are present in some siblings of children with ASD as early as 36 months of age. As the new DSM-5 diagnosis of Social (Pragmatic) Communication Disorder (SCD) is thought to occur more frequently in family members of individuals with ASD, it is possible that some of these siblings will meet criteria for SCD as they get older. Close monitoring of early pragmatic language development in young children at familial risk for ASD is warranted.Journal of Child Psychology and Psychiatry 10/2014; · 5.42 Impact Factor