Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically

Spatial contrast sensitivity in adolescents with autism spectrum disorders

Adolescents with autism spectrum disorders (ASD) and typically developing (TD) controls underwent a rigorous psychophysical assessment that measured contrast sensitivity to seven spatial frequencies (0.5-20 cycles/degree). A contrast sensitivity function (CSF) was then fitted for each participant, from which four measures were obtained: visual acuity, peak spatial frequency, peak contrast sensitivity, and contrast sensitivity at a low spatial frequency. There were no group differences on any of the four CSF measures, indicating no differential spatial frequency processing in ASD. Although it has been suggested that detail-oriented visual perception in individuals with ASD may be a result of differential sensitivities to low versus high spatial frequencies, the current study finds no evidence to support this hypothesis

Commentary: Sex difference differences? A reply to Constantino Dr Meng-Chuan Lai

Messinger et al. found a 3.18 odds ratio of male to female ASD recurrence in 1241 prospectively followed high-risk (HR) siblings. Among high-risk siblings (with and without ASD), as well as among 583 low-risk controls, girls exhibited higher performance on the Mullen Scales of Early Learning, as well as lower restricted and repetitive behavior severity scores on the Autism Diagnostic Observation Schedule (ADOS) than boys. That is, female-favoring sex differences in developmental performance and autism traits were evident among low-risk and non-ASD high-risk children, as well as those with ASD. Constantino (Mol Autism) suggests that sex differences in categorical ASD outcomes in Messinger et al. should be understood as a female protective effect. We are receptive to Constantino's (Mol Autism) suggestion, and propose that quantitative sex differences in autism-related features are keys to understanding this female protective effect

Uneven integration for perception and action cues in children’s working memory

We examined the development of visual cue integration in a desktop working-memory task using boxes with different visual action cues (opening actions) and perceptual surface cues (colours, monochromatic textures, or images of faces). Children had to recall which box held a hidden toy, based on (a) the action cue, (b) the surface cue, or (c) a conjunction of the two. Results from three experiments show a set of asymmetries in children's integration of action and surface cues. The 18–24-month-olds disregarded colour in conjunction judgements with action; 30–36-month-olds used colour but disregarded texture. Images of faces were not disregarded at either age. We suggest that 18–24-month-olds' disregard of colour, seen previously in reorientation tasks (Hermer & Spelke, 1994), may represent a general phenomenon, likened to uneven integration between the dorsal and ventral streams in early development

Clinical Assessment and Management of Toddlers With Suspected Autism Spectrum Disorder: Insights From Studies of High-Risk Infants

With increased public awareness of the early signs and recent American Academy of Pediatrics recommendations that all 18- and 24-month-olds be screened for autism spectrum disorders, there is an increasing need for diagnostic assessment of very young children. However, unique challenges exist in applying current diagnostic guidelines for autism spectrum disorders to children under the age of 2 years. In this article, we address challenges related to early detection, diagnosis, and treatment of autism spectrum disorders in this age group. We provide a comprehensive review of findings from recent studies on the early development of children with autism spectrum disorders, summarizing current knowledge on early signs of autism spectrum disorders, the screening properties of early detection tools, and current best practice for diagnostic assessment of autism spectrum disorders before 2 years of age. We also outline principles of effective intervention for children under the age of 2 with suspected/confirmed autism spectrum disorders. It is hoped that ongoing studies will provide an even stronger foundation for evidence-based diagnostic and intervention approaches for this critically important age group

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