235. State-dependent associations between striatal dopamine transporter availability and large-scale brain network in bipolar disorder

Abstract

Abstract Background Dysregulation of dopamine signaling has been implicated in the pathophysiology of bipolar disorder (BD), yet in vivo evidence linking dopaminergic markers to large-scale brain networks across mood states remains limited. Longitudinal multimodal imaging is needed to clarify these mechanisms. Aims & Objectives We aimed to investigate whether dopamine transporter (DAT) availability differs between euthymic and depressive states in BD, and how striatal DAT availability relates to striatum-based functional connectivity. Method This is a longitudinal within-subject study integrating (99m)Tc-TRODAT-1 SPECT to quantify striatal DAT availability and resting-state functional magnetic resonance imaging to assess striatal-based functional connectivity across mood states. 33 patients with BD were prospectively followed over 3 years to identify transitions into euthymic or depressive states. Participants remained on stable psychotropic regimens, and medications known to alter DAT were excluded. Voxelwise general linear and linear mixed-effects models assessed associations and state interactions between DAT availability, striatal functional connectivity, and depressive-symptom severity, controlling for age and sex with cluster-level family-wise error correction. Results Paired t-tests compared within-subject differences showed significantly lower striatal DAT availability during depressive states compared with euthymia. In euthymia, higher DAT availability was associated with stronger connectivity between the dorsal striatum and salience/sensorimotor regions, including the dorsal anterior cingulate and supramarginal gyri. In depression, DAT availability instead negatively correlated with connectivity to default mode network nodes such as the precuneus and subgenual anterior cingulate. Notably, reduced FC between the dorsal striatum and dorsal anterior cingulate or supramarginal gyrus during depression was associated with greater depressive symptom severity. Discussion & Conclusions Altered striatal DAT availability and its divergent associations with large-scale networks across mood states suggest a potential mechanism linking dopamine dysfunction to affective instability in BD. These findings provide evidence of coordinated molecular and network changes linked to mood expression, warranting further investigation into their causal relationships and therapeutic implications.