DESCRIPTION (provided by applicant): Cognitive, academic, social and psychiatric abnormalities are common in childhood onset epilepsy, with enduring adverse consequences into adulthood, even among those with uncomplicated and remitted epilepsies. To understand the natural history of these lifespan issues, the initial funding cycle of our prospective cohort study (RO1-44351) examined children (ages 8-18) with newly diagnosed idiopathic epilepsies (n=75) and healthy controls (n=62), and followed them for 2 years with neuropsychological, psychiatric, and neuroimaging techniques. While informing the early natural history of cognitive, anatomic, and psychiatric abnormalities of childhood epilepsy, we also identified risk factors at the time of epilepsy diagnosis that predicted developmental trajectories two years following diagnosis. We hypothesize these same abnormalities will predict longer term outcomes in important areas of life performance (e.g., employment, independent living, educational attainment). In this competing renewal application, we propose to follow our original cohort to characterize and predict young adulthood outcomes, enrich the cohort with new onset epilepsy and control participants (n=150), and incorporate new procedures to test hypotheses regarding the effects of family history, disrupted neural circuitry, and epilepsy syndrome on life course. The specific aims of this competing renewal application are as follows: 1) Characterize the longer-term (10- year) social, educational, vocational, and psychiatric trajectories of childhood onset epilepsy and identify predictors of favorable and unfavorable young adult outcomes; 2) Clarify the role of family history to the presence of cognitive and psychiatric comorbidities in children with new onset epilepsy; 3) Characterize the relationship between abnormalities in brain volume, shape and connectivity with disordered cognition and psychiatric status; and 4) Identify syndrome-specific cognitive, psychiatric, and imaging abnormalities. PUBLIC HEALTH RELEVANCE: Childhood epilepsy is a prevalent neurological disorder associated with poor outcomes in key aspects of adult life (e.g., employment and finances; marriage and family; social and psychiatric status), but the predictors of these outcomes remain poorly understood. The results of this controlled prospective cohort investigation will provide what we believe are the earliest insights into the natural history of these problematic lifespan outcomes.

Childhood epilepsy is a prevalent neurological disorder associated with poor outcomes in key aspects of adult life (e.g., employment and finances; marriage and family; social and psychiatric status), but the predictors of these outcomes remain poorly understood. The results of this controlled prospective cohort investigation will provide what we believe are the earliest insights into the natural history of these problematic lifespan outcomes.