Joint engagement modulates object discrimination in toddlers: a pilot electrophysiological investigation

Joint engagement (JE) is a state in which two people attend to a common target. By supporting an infant’s attention to the target, JE promotes encoding of information. This process has not been studied in toddlers despite the fact that language and social interaction develop rapidly in this period. We asked whether JE modulates object discrimination in typically developing toddlers. In a pilot evaluation of a novel, naturalistic paradigm, toddlers (n = 11) were introduced to toys by an examiner with or without JE. Toddlers then viewed images of the toys while high-density electroencephalography (EEG) was recorded. Analysis focused on the differential neural response to objects presented in the two conditions. EEG components of interest included frontal positive component (Pb), negative component (Nc), and positive slow wave. Toddlers discriminated between conditions with a larger Pb peak amplitude to stimuli presented with JE and a larger Nc mean amplitude to the stimuli presented without JE, reflecting greater familiarity with the toys presented socially. Our findings suggest that JE supports object learning in toddlers, and supports the potential utility of this novel paradigm in both the assessment and the potential to detect impairment in social learning among toddlers

Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study

Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0027-y) contains supplementary material, which is available to authorized users

Play and Developmental Outcomes in Infant Siblings of Children with Autism

We observed infant siblings of children with autism later diagnosed with ASD (ASD siblings; n = 17), infant siblings of children with autism with and without other delays (Other Delays and No Delays siblings; n = 12 and n = 19, respectively) and typically developing controls (TD controls; n = 19) during a free-play task at 18 months of age. Functional, symbolic, and repeated play actions were coded. ASD siblings showed fewer functional and more non-functional repeated play behaviors than TD controls. Other Delays and No Delays siblings showed more non-functional repeated play than TD controls. Group differences disappeared with the inclusion of verbal mental age. Play as an early indicator of autism and its relationship to the broader autism phenotype is discussed

Behavioral Profiles of Affected and Unaffected Siblings of Children with Autism: Contribution of Measures of Mother–Infant Interaction and Nonverbal Communication

We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months

Common genetic variants on 5p14.1 associate with autism spectrum disorders

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)—two genes encoding neuronal cell-adhesion molecules—revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 × 10−8, odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 × 10−8 to 2.1 × 10−10. Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs

Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes

The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11–q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3×10−5). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3×10−4). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3×10−39), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts

Early pragmatic language difficulties in siblings of children with autism: implications for DSM‐5 social communication disorder?

BackgroundWe 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.MethodsParticipants 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 10(th) 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 10(th) 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%).ConclusionsPragmatic 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

Atypical gaze following in autism : a comparison of three potential mechanisms

In order to evaluate the following potential mechanisms underlying atypical gaze following in autism, impaired reflexive gaze following, difficulty integrating gaze and affect, or reduced understanding of the referential significance of gaze, we administered three paradigms to young children with autism (N = 21) and chronological (N = 21) and nonverbal mental age (N = 21) matched controls. Children with autism exhibited impaired reflexive gaze following. The absence of evidence of integration of gaze and affect, regardless of diagnosis, indicates ineffective measurement of this construct. Reduced gaze following was apparent among children with autism during eye-tracking and in-person assessments. Word learning from gaze cues was better explained by developmental level than autism. Thus, gaze following may traverse an atypical, rather than just delayed, trajectory in autism