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<p>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 [<sup>18</sup>F]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 (<i>P</i> = 0.016), but not in caudate or putamen, driving a significant group × region interaction (<i>P</i> = 0.012). Within the depressed group, greater depression severity was paradoxically associated with higher ventral striatal DAT binding (<i>P</i> = 0.039). These findings provide in vivo evidence linking ventral striatal dopaminergic dysfunction to PD-MDD, advancing mechanistic understanding relevant for treatment development.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Jessica E. M. C. Dirkx,
  • Filip Grill,
  • Nienke Dijk,
  • Roshan Cools,
  • Jan Booij,
  • Bastiaan R. Bloem,
  • Rick C. G. Helmich,
  • Henricus G. Ruhé,
  • Maria H. C. T. van Beek

摘要

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.