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Franchesca Kuhney, Ph.D., Winner of the 2018 NIMH Three-Minute Talks Competition


FRANCESCA KUHNEY: Today, I'm going to talk to you about how genes impact brain development, and one approach that we can take to understanding this is a very rare genetic disorder called Williams Syndrome. Williams Syndrome allows us to study genetic influence on the brain in a very special way because it's clearly defined and very specific genetic and clinical profiles. Williams Syndrome is caused by a hemi deletion of approximately 25 genes on chromosome seven and results in a very specific pattern of hyper sociability, non-social anxiety, and cognitive deficits. So, by setting this very specific genetic deletion in its resulting impact on brain development we can better understand how genes work through the brain to result in complex behaviors.

The amygdala highlighted in red and the hippocampus highlighted in green are involved in emotion regulation and cognition respectively. Adults with Williams Syndrome have shown altered activation patterns, metabolism, and shape in these structures compared to healthy adults. And while it's known that the genetic features of Williams Syndrome impact brain development, the details of this process have not been studied in children over time. So, I wanted to know how the relative volume of the hippocampus and amygdala differ in children's Williams Syndrome compared to typically developing children across adolescence.

Each line on this plot represents a child that participated in our longitudinal study. In each dot on that line represents one of their two-year visits at which structural MRI scans were collected. These scans were longitudinally processed, and the hippocampus and amygdala were segmented to estimate their volume. These volumes were then normalized and applied to growth curve models which estimate nonlinear longitudinal trajectories. These graphs represent growth curve models of volume of the hippocampus and amygdala with volume on the y axis and age on the x axis. These are absolute volumes, and we can see that children with Williams syndrome have a smaller amygdala and hippocampus compared to typically developing children over time.

However, people with Williams Syndrome have a smaller total brain volume and it's important to consider these data in the context of this fact. So, now, I will show you these data normalized by total brain volume and we can see that children with Williams syndrome actually have a larger percentage of their brains dedicated to the hippocampus and amygdala compared to typically developing children over time. These data provide early indication of the structural differences seen in the hippocampus and amygdala and can be related to these social and cognitive phenotypes seen in Williams Syndrome adults. Future work will investigate the relationship between these findings and neuropsychological tests and anxiety scales because little is known about how the brain changes across childhood and adolescence and how genes influence this process. This longitudinal study of Williams syndrome begins to shed light on the complex neuro genetic mechanisms underlying adolescent brain development as a whole. Thank you.