Executive function in adolescents with and at-risk for bipolar disorder

Bipolar disorder is a serious psychiatric illness that is characterized by mania. Many patents with bipolar disorder also exhibit significant deficits in cognitive processing across multiple domains, including executive function. The research included here attempts to better characterize the deficits in youth with and at-risk for bipolar disorder in two executive function subdomains, sustained attention and interference control.;Chapter 3 presents the results of a behavioral study using a modified version of the flanker task to assess sustained attention in youth with bipolar disorder. Results showed that youth with bipolar disorder had deficits in interference control that were detected as increased reaction time and decreased accuracy on incongruent trials. An analysis of effects associated with conflict-driven adaptation did not yield significant results.;Chapter 4 presents the results of an imaging study which attempted to characterize the neural correlates of the behavioral deficits demonstrated in Chapter 3. Youth with bipolar disorder, youth at-risk for bipolar disorder, and healthy youth were recruited to participate in an fMRI study using a modified version of the arrow flanker task. The groups performed similarly on all behavioral measures, and all groups showed similar patterns of activation in BA 46 and the dorsal anterior cingulate. However, there were significant differences in functional activation patterns cross several of the regions considered. Youth with mania showed decreased activation in left BA 11/12 and the right anterior insula relative to those without bipolar disorder. Those at-risk for bipolar disorder who had not yet developed mania showed increased recruitment of BA 10 on the left and right subgenual and pregenual cingulate. Those with a family history of bipolar disorder showed an altered pattern of caudate recruitment regardless of diagnosis.;Together these studies demonstrate that executive function may serve as a reasonable intermediate phenotype for future research in bipolar disorder. Larger sample sizes and more detailed assessment of symptoms and cognitive function will help to determine if the alterations detected represent risk factors, markers of resilience, or endophenotypes, and if these markers can have clinical utility in predicting illness onset, prognosis, or medication response.;Chapter 2A contains the results of an imaging study of sustained attention in bipolar youth, which was conducted concurrently with a double-blind, placebo-controlled study of ziprasidone for the treatment of mania in adolescents. Results showed that compared with placebo, treatment with ziprasidone was associated with greater increases in activation in Brodmann areas (BA) 11 and 47. Patients who subsequently responded to ziprasidone also showed significantly greater deactivation in right BA 47 prior to treatment, and the activation in this region at baseline was negatively correlated with symptom improvement. Similarly, Chapter 2B contains the results of an imaging study using the same sustained attention task, which was conducted concurrently with an open-label study of carbamazepine for the treatment of mania in adolescents. In this study, treatment with carbamazepine was associated with increases in activation in BA 10.