Depression in Parkinson's disease is associated with reduced ventral striatal dopamine transporter binding

Major depressive disorder (MDD) is a common non-motor symptom in Parkinson's disease (PD), affecting one third of patients. Dopaminergic deficits have been hypothesised to contribute to PD-MDD, but direct molecular evidence is limited. In this cross-sectional study, we compared striatal dopamine transporter (DAT) binding between 22 depressed (DSM-5) and 34 well-matched non-depressed PD patients using [¹⁸F]FE-PE2I PET. The striatum was segmented into ventral striatum, medial caudate, anterior putamen and posterior putamen. Mixed-effect models included region, hemisphere, and group as fixed effects, and subject ID as random effect. PD-MDD patients showed lower DAT binding in the ventral striatum (P = 0.016), but not in caudate or putamen, driving a significant group × region interaction (P = 0.012). Within the depressed group, greater depression severity was paradoxically associated with higher ventral striatal DAT binding (P = 0.039). These findings provide in vivo evidence linking ventral striatal dopaminergic dysfunction to PD-MDD, advancing mechanistic understanding relevant for treatment development.