Neurobiological Origins of Autism Heterogeneity

Pat Levitt, Ph.D. Simms/Mann Chair in Developmental Neurogenetics, Children’s Hospital Los Angeles and the WM Keck Provost Professor in Neurogenetics, Keck School of Medicine of USC Typically developing individuals exhibit broad heterogeneity in cognitive, social and emotional behaviors. While neuroscientists are still struggling with understanding the mechanisms that underlie this heterogeneity, the field now has recognized that individual differences even between two individuals with the same categorical neurodevelopmental diagnosis, can be profound. Thus, the identical causal mutation often leads to clinical symptoms that may differ widely in those who are affected. These differences, in turn, create challenges for implementing the most effective clinical treatments. Studies will be presented that address the biological nodes that contribute to functional heterogeneity. Experiments address the heritable contributions to behavioral heterogeneity broadly, and that different components of complex behavior may be impacted by distinct genetic factors. Moreover, studies address molecular and cellular mechanisms that underlie neurodevelopmental trajectories of vulnerable circuits, and the importance of timing of maturation in these developmental processes that may contribute to heterogeneity. This research informs new ideas regarding the capacity for change, and the importance of incorporating best practices that do not use the ‘one size fits all’ approach to treatment of children, adolescents and adults with neurodevelopmental disorders.