Project 3: Long-Term Effect of Early Anxious Temperament on Human Neural Development

PI: H. Hill Goldsmith

Understanding the early origins as well as the brain bases for conditions such as anxiety and depression is an important priority for public health. These issues can be addressed in studies that carefully assess behavior and brain structure and function beginning in infancy and extending through adolescence. Employing identical twins in this research allows control of genetic differences that affect development.

Project 3 incorporates two distinct studies, each of which capitalizes on extensive longitudinal, affective behavioral phenotyping during infancy or early childhood to study early adult outcomes based on neuroimaging (Study 1) or induced pluripotent stem cells. Study 1's monozygotic (MZ) twin difference design allows us to distinguish whether observed differences in later brain structure and function are associated with environmental influences versus familial influences on early anxious temperament. The comparison of MZ cotwins, with their age-matched, grossly similar brain morphology, allows detection of more subtle MRI effects in humans than any competing non-experimental design. Study 2 is a pilot study that is coordinated with the nonhuman primate stem cell work in Project 1. We examine whether young adults who are slow in amygdala recovery to negative affect elicitation and chronically anxious differ from those selected to be rapid in amygdala recovery and non-anxious differ in gene expression and cellular electrophysiology of GABAergic neurons that are derived from induced pluripotent stem cells.

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