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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 [\n                    <jats:sup>18<\/jats:sup>\n                    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 (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.016), but not in caudate or putamen, driving a significant group\u2009\u00d7\u2009region interaction (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.012). Within the depressed group, greater depression severity was paradoxically associated with higher ventral striatal DAT binding (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.039). These findings provide in vivo evidence linking ventral striatal dopaminergic dysfunction to PD-MDD, advancing mechanistic understanding relevant for treatment development.\n                  <\/jats:p>","DOI":"10.1038\/s41531-026-01363-2","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T16:55:01Z","timestamp":1779728101000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Depression in Parkinson\u2019s disease is associated with reduced ventral striatal dopamine transporter binding"],"prefix":"10.1038","volume":"12","author":[{"given":"Jessica E. M. 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R.C. is funded by an ERC Advanced Grant CHEMCONTROL #101054532, and acts as a consultant with Roche Ltd, but has no shares. J.B. is a consultant with GE Healthcare (all related payments to the institute). B.B. serves as the co-Editor in Chief for the Journal of Parkinson\u2019s disease and serves on the editorial board of Practical Neurology and Digital Biomarkers. B.B. was not involved in the journal\u2019s review of, or decisions related to, this manuscript. B.B. has received fees from serving on the scientific advisory board for the Critical Path Institute, Gyenno Science, MedRhythms, UCB, Kyowa Kirin and Zambon (paid to the institute), has received fees for speaking at conferences from AbbVie, Bial, Biogen, GE Healthcare, Oruen, Roche, UCB and Zambon (paid to the Institute), has received research support from Biogen, Cure Parkinson\u2019s, Davis Phinney Foundation, Edmond J. Safra Foundation, Fred Foundation, Gatsby Foundation, Hersenstichting Nederland, Horizon 2020, IRLAB Therapeutics, Maag Lever Darm Stichting, Michael J Fox Foundation, Ministry of Agriculture, Ministry of Economic Affairs & Climate Policy, Ministry of Health, Welfare and Sport, Netherlands Organization for Scientific Research (ZonMw), Not Impossible, Parkinson Vereniging, Parkinson\u2019s Foundation, Parkinson\u2019s UK, Stichting Alkemade-Keuls, Stichting Parkinson NL, Stichting Woelse Waard, Health Holland\/Topsector Life Sciences and Health, UCB, Verily Life Sciences, Roche and Zambon, and does not hold any stocks or stock options with any companies that are connected to Parkinson\u2019s disease or any of his clinical or research activities. 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