State-dependent associations between striatal dopamine transporter availability and large-scale functional networks in bipolar disorder: An exploratory multimodal imaging study.

BACKGROUND: Dopaminergic dysregulation has been implicated in the pathophysiology of bipolar disorder (BD), yet how state-dependent alterations in presynaptic dopaminergic markers relate to large-scale brain networks remains unclear. We aimed to examine longitudinal, within-subject associations between striatal dopamine transporter (DAT) availability and functional connectivity (FC) across mood states in BD. METHODS: Outpatients with BD underwent repeated neuroimaging during euthymic and depressive states. Striatal DAT availability was measured using ^99mTc-TRODAT-1 single-photon emission computed tomography, and resting-state functional magnetic resonance imaging was used to assess striatal seed-based FC. Paired t tests compared DAT availability across mood states. General linear and linear mixed models examined DAT-FC associations and DAT-mood interactions, adjusting for age and sex. RESULTS: Thirty-three patients were enrolled. Within-individual analyses showed lower bilateral dorsal-striatal DAT availability during depression than euthymia. During euthymia, DAT availability was associated with stronger dorsal striatum connectivity with the dorsal and middle cingulate regions, whereas during depression it was negatively associated with connectivity to the precuneus. Linear mixed models showed mood-dependent associations of dorsal-striatal DAT availability with connectivity involving the precuneus, insula, and supramarginal gyrus. Reduced dorsal striatum-ACC and supramarginal connectivity during depression was associated with greater depressive symptom severity. CONCLUSION: Striatal DAT availability and cortico-striatal functional connectivity showed coordinated, state-dependent changes in BD. These findings provide evidence for state-dependent associations between presynaptic dopaminergic markers and large-scale functional networks in BD.