Neurostructural and neurocognitive correlates of APOE epsilon 4 in youth bipolar disorder

Background: Bipolar disorder (BD) is a clinical risk factor for Alzheimer's disease (AD). Apolipoprotein E epsilon 4 (APOE epsilon 4), a genetic risk factor for AD, has been associated with brain structure and neurocognition in healthy youth.Aims: We evaluated whether there was an association between APOE epsilon 4 with neurostructure and neurocognition in youth with BD.Methods: Participants included 150 youth (78 BD:19 epsilon 4-carriers, 72 controls:17 epsilon 4-carriers). 3T-magnetic resonance imaging yielded measures of cortical thickness, surface area, and volume. Regions-of-interest (ROI) and vertex-wise analyses of the cortex were conducted. Neurocognitive tests of attention and working memory were examined.Results: Vertex-wise analyses revealed clusters with a diagnosis-by-APOE epsilon 4 interaction effect for surface area (p = 0.002) and volume (p = 0.046) in pars triangularis (BD epsilon 4-carriers > BD noncarriers), and surface area (p = 0.03) in superior frontal gyrus (controls epsilon 4-carriers > other groups). ROI analyses were not significant. A significant interaction effect for working memory (p = 0.001) appeared to be driven by nominally poorer performance in BD epsilon 4-carriers but not control epsilon 4-carriers; however, post hoc contrasts were not significant.Conclusions: APOE epsilon 4 was associated with larger neurostructural metrics in BD and controls, however, the regional association of APOE epsilon 4 with neurostructure differed between groups. The role of APOE epsilon 4 on neurodevelopmental processes is a plausible explanation for the observed differences. Future studies should evaluate the association of APOE epsilon 4 with pars triangularis and its neurofunctional implications among youth with BD.