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Excess tau PET ligand retention in elderly patients with major depressive disorder

Abstract

Depression is one of the common psychiatric disorders in old age. Major depressive disorder (MDD) has been identified as a risk factor or prodrome for neurodegenerative dementias, suggesting neuropathological overlaps and a continuum between MDD and neurodegenerative disorders. In this study, we examined tau and amyloid-β (Aβ) accumulations in the brains of MDD and healthy controls using positron emission tomography (PET) to explore pathological substrates of this illness. Twenty MDD and twenty age-matched, healthy controls were examined by PET with a tau radioligand, [11C]PBB3, and an Aβ radioligand, [11C]PiB. Radioligand retentions were quantified as a standardized uptake value ratio (SUVR). We also assessed clinical manifestations of the patients using the 17-item Hamilton Depression Scale, the Geriatric Depression Scale, and psychotic symptoms. Mean cortical [11C]PBB3 SUVRs in MDD patients were significantly higher than those of healthy controls. These values were higher in MDD patients with psychotic symptoms than in those without any. The present findings indicate that tau depositions may underlie MDD, and especially in patients with psychotic symptoms. PET detection of tau accumulations may provide mechanistic insights into neuronal dysfunctions in these cases and could serve as predictions of their clinical consequences.

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Fig. 1: [11C]PBB3 SUVRs in MDD and healthy controls.
Fig. 2: [11C]PiB SUVRs in MDD and healthy controls.

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Acknowledgements

We thank Takamasa Maeda and the members of the Brain Disorder Translational Research Group for their support with PET scans, Kazuko Suzuki, and Shizuko Kawakami for their assistance as clinical coordinators, Hiromi Sano and Naoto Sato for their support with MRI scans, the staff of the Department of Radiopharmaceuticals Development for their radioligand synthesis and metabolite analysis, Yoshihide Akine, Bun Yamagata, and Jinichi Hirano for recruiting subjects and Renpei Sengoku in Tokyo Metropolitan Geriatric Hospital, and Institute of Gerontology for accessing Brain Bank data. We also thank Takashi Horiguchi for his assistance as a research administrator. Sho Moriguchi has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

This research was partly supported by AMED under Grant Number JP17dm0107094.

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Contributions

Study concept and design: SM, KT, TS, and MM. Acquisition, analysis, or interpretation of data: SM, KT, MK, SK, YK, KT, RT, HT, JHM, MM, and KK. Drafting of the manuscript: SM, KT, MK, TS, and MH. Critical revision of the manuscript for important intellectual content: SM, KT, MK, MM, TS, MH, and SM. Statistical analysis: SM and KT. Obtained funding: KT, TS, and MH. Administrative, technical, or material support: YK, KK, M-RZ, TS, and MH.

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Correspondence to Sho Moriguchi.

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Conflict of interest

HS, M-RZ, TS, and MH hold a patent on compounds related to the present report (JP 5422782/EP 12 884 742.3). The other authors report no disclosures relevant to the manuscript.

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Moriguchi, S., Takahata, K., Shimada, H. et al. Excess tau PET ligand retention in elderly patients with major depressive disorder. Mol Psychiatry 26, 5856–5863 (2021). https://doi.org/10.1038/s41380-020-0766-9

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