Searching for biomarkers and behavioral signs of early risk for neurodevelopmental disorders has emerged as an important line of clinical research in an effort to improve diagnosis and develop the most effective treatments and preventive interventions. In our current award period we identified several significant differences between infants at high familial risk for ASD (defined as having an older sibling with the disorder) and low risk control infants, including alterations in EEG, atypical lateralization for speech and faces, and reduced cortical connectivity all of which might serve as early risk markers. These differences were not only identified during the first year of life, their developmental trajectories were also atypical; a finding that appears to be a hallmark of risk for ASD. Our findings open up important questions about whether these risk markers extend to other infants later diagnosed with ASD, particularly infants from the general population, and whether they might also serve as risk markers for other related disorders, particularly language and social communication delay. In the next award period we address these questions by adding a new group of infants who fail a developmental screener (the CSBS) at 12 months. This group will be drawn from general pediatric practices, and will be compared to high-risk infant siblings and low risk controls on a battery of electrophysiological and behavioral measures that will be administered at 12-14 months, and again at 18, 24 and 36 months, at which time diagnostic outcomes will be evaluated. The project will address two specific aims. First, Do neural and behavioral risk markers (and their developmental trajectories) that distinguish infants at familial risk for ASD from low risk controls extend to infants at risk based on early behavioral differences detected on a 12-month screening instrument? We hypothesize that some risk markers will be shared across both high-risk groups, though for the screened group this may only hold for infants with clinical outcomes and show different developmental trajectories. Other risk markers may be unique to infants at familial risk.
Our second aim addresses the question: Do the developmental profiles of neural and behavioral risk markers we identify predict only to later diagnoses of ASD or do they extend to other non-ASD neurodevelopmental outcomes at 36 months, including language or social communication delay? We hypothesize that some of our risk markers will be shared across these non-ASD related (and overlapping) clinical outcomes, while others will be unique to ASD outcomes. As research progresses on identifying behavioral and neural markers in infants that are at risk for neurodevelopment disorders, it is critical that we extend our research beyond familial risk to the general population and to evaluate risk markers across several diagnostic outcomes. In this way our goal is to advance knowledge of the shared and unique mechanisms that can ultimately be the focus of more targeted interventions at a time when there is greatest plasticity and opportunity for preventing adverse outcomes.
This project is designed to detect the earliest behavioral and brain risk markers for autism spectrum disorder and related language and social communication delays. The findings will have a major influence in developing novel approaches to early screening and diagnoses for these disorders. In turn, infants and toddlers identified as showing significant risk signs at much younger ages will be able to take advantage of early interventions that may prevent the onset of clinically significant symptoms or reduce the severity of the disorder.
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