Striatal functional alterations link to distinct symptomatology across mood states in bipolar disorder

Background As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. Methods Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive and 31 euthymic patients with BD, and 32 healthy controls. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy controls and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. Results Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen (VRP) and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased VRP connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms and worse cognitive performance). Bipolar (hypo)manic patients had the highest FC and behavioral composite scores while bipolar depressive patients had the lowest. Conclusions Our data demonstrated both trait features of BD and state features specific to bipolar (hypo) mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.