White Matter, Cognition, and Electrophysiological Variables in Bipolar Disorder: Using Multimodal Integration of Biomarker Variables Associated With Bipolar Disorder to Elucidate Deficits

AIM: This study aimed to evaluate associations in bipolar disorder (BD) across multimodal measures of white matter microstructure (using diffusion tensor imaging; DTI), cognitive, behavioral, and brain electrophysiological measures (using electroencephalography; EEG). METHODS: Subjects were recruited through the Psychosis and Affective Research Domains and Intermediate Phenotypes Consortium (n = 45 bipolar with psychosis, n = 40 bipolar without psychosis, n = 66 healthy subjects). DTI data were used to quantify the white matter variables, fractional anisotropy (FA) and radial diffusivity (RD). The Brief Assessment of Cognition in Schizophrenia (BACS), Stop Signal Task (SST), pro- and anti-saccades, auditory event-related potentials (ERPs), and intrinsic brain activity were used as estimates of brain function. RESULTS: The combined BD group differed from healthy controls, but no differences between BD with and without psychosis were observed. BD-related white matter abnormalities were seen across multiple tracts: right cingulum-cingulate gyrus, bilateral anterior thalamic radiation, bilateral superior longitudinal fasciculus, right inferior longitudinal fasciculus, and forceps major. Results also showed modestly compromised cognitive performance and elevated intrinsic EEG activity associated with BD. CONCLUSIONS: Further analysis indicated worse white matter integrity related to higher intrinsic EEG and modestly higher ERPs. These multimodal analyses are likely to aid in creating future informative diagnostic, etiological, and treatment targets for BD.