Parent-infant interaction in infant siblings at risk of autism

Recent models of the early emergence of autism spectrum disorder (ASD) propose an interaction between risk susceptibility and the infant's social environment, resulting in a progressively atypical developmental trajectory. The infant's early social environmental experience consists mostly of interaction with caregivers, yet there has been little systematic study of early parent-infant interaction in infants at risk of ASD. This study examined the global characteristics of parent-infant interaction in 6- to 10-month-old infants with an older sibling diagnosed with ASD (at-risk sibs), in comparison with a group of infants with no family history of ASD (low-risk sibs). As part of the British Autism Study of Infant Siblings (BASIS), 6-min videotaped unstructured play interactions of mother-infant dyads (45 at-risk sibs and 47 low-risk sibs) were rated on global aspects of parent-infant interaction, blind to participant information. Differences in global characteristics of interaction were observed in both infant and parent contributions in the at-risk group compared to low-risk controls. In analyses adjusted for age and developmental level, at-risk sib infants were less lively, and their parents showed higher directiveness, and lower sensitive responding (as a trend after adjustment). Level of infant liveliness was independent of other interactive behaviour. Consistent with reports in previous literature in older children with autism and in other neurodevelopmental disorders, our findings may suggest that infants at genetic risk are exposed to a more directive interactive style relatively early in infancy. We discuss possible explanations for these findings and implications for further developmental study and intervention. (C) 2012 Elsevier Ltd. All rights reserved.</p

Neurocognitive and observational markers: prediction of autism spectrum disorder from infancy to mid-childhood

Background Prospective studies of infants at high familial risk for autism spectrum disorder (ASD) have identified a number of putative early markers that are associated with ASD outcome at 3 years of age. However, some diagnostic changes occur between toddlerhood and mid-childhood, which raises the question of whether infant markers remain associated with diagnosis into mid-childhood. Methods First, we tested whether infant neurocognitive markers (7-month neural response to eye gaze shifts and 14-month visual disengagement latencies) as well as an observational marker of emerging ASD behaviours (the Autism Observation Scale for Infants; AOSI) predicted ASD outcome in high-risk (HR) 7-year-olds with and without an ASD diagnosis (HR-ASD and HR-No ASD) and low risk (LR) controls. Second, we tested whether the neurocognitive markers offer predictive power over and above the AOSI. Results Both neurocognitive markers distinguished children with an ASD diagnosis at 7 years of age from those in the HR-No ASD and LR groups. Exploratory analysis suggested that neurocognitive markers may further differentiate stable versus lost/late diagnosis across the 3 to 7 year period, which will need to be tested in larger samples. At both 7 and 14 months, combining the neurocognitive marker with the AOSI offered a significantly improved model fit over the AOSI alone. Conclusions Infant neurocognitive markers relate to ASD in mid-childhood, improving predictive power over and above an early observational marker. The findings have implications for understanding the neurodevelopmental mechanisms that lead from risk to disorder and for identification of potential targets of pre-emptive intervention

Face engagement during infancy predicts later face recognition ability in younger siblings of children with autism

Face recognition difficulties are frequently documented in children with autism spectrum disorders (ASD). It has been hypothesized that these difficulties result from a reduced interest in faces early in life, leading to decreased cortical specialization and atypical development of the neural circuitry for face processing. However, a recent study by our lab demonstrated that infants at increased familial risk for ASD, irrespective of their diagnostic status at 3 years, exhibit a clear orienting response to faces. The present study was conducted as a follow-up on the same cohort to investigate how measures of early engagement with faces relate to face-processing abilities later in life. We also investigated whether face recognition difficulties are specifically related to an ASD diagnosis, or whether they are present at a higher rate in all those at familial risk. At 3 years we found a reduced ability to recognize unfamiliar faces in the high-risk group that was not specific to those children who received an ASD diagnosis, consistent with face recognition difficulties being an endophenotype of the disorder. Furthermore, we found that longer looking at faces at 7 months was associated with poorer performance on the face recognition task at 3 years in the high- risk group. These findings suggest that longer looking at faces in infants at risk for ASD might reflect early face-processing difficulties and predicts difficulties with recognizing faces later in life

Global prevalence of autism and other pervasive developmental disorders

We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries

Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years

Background: There has been increasing interest in the potential for pre-emptive interventions in the prodrome of autism, but little investigation as to their effect. Methods: A two-site, two-arm assessor-blinded randomised controlled trial (RCT) of a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting), against no intervention. Fifty-four infants (28 intervention, 26 nonintervention) at familial risk of autism but not otherwise selected for developmental atypicality were assessed at 9-month baseline, 15-month treatment endpoint, and 27- and 39-month follow-up. Primary outcome: severity of autism prodromal symptoms, blind-rated on Autism Observation Schedule for Infants or Autism Diagnostic Observation Schedule 2nd Edition across the four assessment points. Secondary outcomes: blind-rated parent–child interaction and child language; nonblind parent-rated communication and socialisation. Prespecified intention-to-treat analysis combined estimates from repeated measures within correlated regressions to estimate the overall effect of the infancy intervention over time. Results: Effect estimates in favour of intervention on autism prodromal symptoms, maximal at 27 months, had confidence intervals (CIs) at each separate time point including the null, but showed a significant overall effect over the course of the intervention and follow-up period (effect size [ES] = 0.32; 95% CI 0.04, 0.60; p = .026). Effects on proximal intervention targets of parent nondirectiveness/synchrony (ES = 0.33; CI 0.04, 0.63; p = .013) and child attentiveness/communication initiation (ES = 0.36; 95% CI 0.04, 0.68; p = .015) showed similar results. There was no effect on categorical diagnostic outcome or formal language measures. Conclusions: Follow-up to 3 years of the first RCT of a very early social communication intervention for infants at familial risk of developing autism has shown a treatment effect, extending 24 months after intervention end, to reduce the overall severity of autism prodromal symptoms and enhance parent–child dyadic social communication over this period. We highlight the value of extended follow-up and repeat assessment for early intervention trials

Infant Neural Sensitivity to Dynamic Eye Gaze Relates to Quality of Parent–Infant Interaction at 7-Months in Infants at Risk for Autism

Links between brain function measures and quality of parent–child interactions within the early developmental period have been investigated in typical and atypical development. We examined such links in a group of 104 infants with and without a family history for autism in the first year of life. Our findings suggest robust associations between event related potential responses to eye gaze and observed parent–infant interaction measures. In both groups, infants with more positive affect exhibit stronger differentiation to gaze stimuli. This association was observed with the earlier P100 waveform component in the control group but with the later P400 component in infants at-risk. These exploratory findings are critical in paving the way for a better understanding of how infant laboratory measures may relate to overt behavior and how both can be combined in the context of predicting risk or clinical diagnosis in toddlerhood

Ethical dimensions of translational developmental neuroscience research in autism

Background Since the 1990s, increasing research has been devoted to the identification of biomarkers for autism to help attain more objective diagnosis; enable early prediction of prognosis; and guide individualized intervention options. Early studies focused on the identification of genetic variants associated with autism, but more recently, research has expanded to investigate neurodevelopmental markers. While ethicists have extensively discussed issues around advances in autism genomics, much less ethical scrutiny has focused on research on early neurodevelopment and on the interventions being developed as a result. Objectives We summarize the current state of the science on the identification of early markers for autism and its potential clinical applications, before providing an overview of the ethical issues arising from increasing understanding of children's neurodevelopment in very early life. Results Advances in the understanding of brain and behavioral trajectories preceding later autism diagnosis raise ethical concerns around three themes: (a) New models for understanding autism; (b) Risks and benefits of early identification and intervention; and (c) Communication of early concerns to families. These ethical issues should be further investigated in research conducted in partnership with autistic people and their families. Conclusions This paper highlights the need for ethical scrutiny of early neurodevelopmental research in autism. Scrutiny requires expertise and methods from the basic sciences and bioethics, as well as constructive collaborations among autistic people, their parents, and autism researchers to anticipate early interventions that serve the community's interests and accommodate the varied experiences and preferences of people on the spectrum and their families.</p

Early and persistent motor delay in infants at-risk of developing autism spectrum disorder: A prospective study

The aim was to build a profile of motor development in infant siblings of children diagnosed with autism. Infants at high familial risk of developing autism spectrum disorder and those at low-risk were tested longitudinally between 6 and 24 months. Data were analysed from the gross and fine motor scales of the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scales at three age points. Low-risk and at-risk infants differed significantly on motor scales at all three visits, with significantly lower motor scores in the at-risk group evident from the age of 6 months based on parental report. Poorer gross and fine motor skills in the at-risk group were only evident on the direct standardised assessment from 12 months. Only gross motor scores were highly correlated across the two measures. A combination of standardised assessments and parental reports may therefore provide the best method for early identification of motor atypicalities in the broader autism phenotype

Structural Templates for Imaging EEG Cortical Sources in Infants

Electroencephalographic (EEG) source reconstruction is a powerful approach that allows anatomical localization of electrophysiological brain activity. Algorithms used to estimate cortical sources require an anatomical model of the head and the brain, generally reconstructed using magnetic resonance imaging (MRI). When such scans are unavailable, a population average can be used for adults, but no average surface template is available for cortical source imaging in infants. To address this issue, we introduce a new series of 13 anatomical models for subjects between zero and 24 months of age. These templates are built from MRI averages and boundary element method (BEM) segmentation of head tissues available as part of the Neurodevelopmental MRI Database. Surfaces separating the pia mater, the gray matter, and the white matter were estimated using the Infant FreeSurfer pipeline. The surface of the skin as well as the outer and inner skull surfaces were extracted using a cube marching algorithm followed by Laplacian smoothing and mesh decimation. We post-processed these meshes to correct topological errors and ensure watertight meshes. Source reconstruction with these templates is demonstrated and validated using 100 high-density EEG recordings from 7-month-old infants. Hopefully, these templates will support future studies on EEG-based neuroimaging and functional connectivity in healthy infants as well as in clinical pediatric populations