This revised NIMH Small Grant (R03) Award application is to support a preliminary investigation of executive functioning ability in children genetically at risk to develop bipolar disorder (BPD). BPD in children and adolescents is increasingly recognized as a common disorder with significant morbidity and mortality. It has been suggested that children with BPD may have a strong genetic vulnerability to develop this disorder and also may exhibit a particularly virulent form of the disorder. In addition to their mood symptoms, there is strong evidence that patients with BPD demonstrate cognitive dysfunction. Furthermore, a small number of reports suggest that cognitive deficits are evident in adults and children who are at genetic risk for BPD but who, at the time of evaluation, have not developed mood syndromes. Cognitive deficits are of direct clinical relevance because they are known to be associated with impairment in completing activities required for successful everyday functioning, including academic and vocational activities. In addition, cognitive dysfunction in individuals who are genetically at risk for BPD has strong theoretical importance because it may provide information about inherited features of mood syndromes, inform theories about the neurophysiological basis of mood disorders, and may potentially be evaluated in the future as one marker that could contribute to the early detection of individuals who are at the strongest risk of developing BPD. Previous work from our laboratory suggests that children at genetic risk for BPD have executive functioning deficits, including impairment in planning, problem-solving, and inhibition. The proposed study will compare the abilities of at-risk children who have mood syndromes, at-risk children without mood syndromes, and a control group of children of parents without a mood disorder on tests of specific component processes of executive functioning. A secondary aim of the study is examine, through parent and teacher ratings, whether children at risk for BPD with and without mood syndromes exhibit impairment in activities of daily living that are thought to be dependent on the integrity of executive functioning skills, and to examine the relationship between these functional deficits and performance on neuropsychological tests of executive ability.
