123I-FP-CIT uptake and behavioral disinhibition in the frontotemporal dementia spectrum: an exploratory DAT-SPECT study.
123I-FP-CIT uptake and behavioral disinhibition in the frontotemporal dementia spectrum: an exploratory DAT-SPECT study.
Where did the research take place?
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Osaka, JP · Author affiliation
Department of Psychiatry, The University of Osaka Hospital, 2-2 D3 Yamadaoka, Suita, 565-0871, Osaka, Japan. skatakami@psy.med.osaka-u.ac.jp.Location evidence
Suita, JP · Author affiliation
Department of Psychiatry, The University of Osaka Hospital, 2-2 D3 Yamadaoka, Suita, 565-0871, Osaka, Japan. skatakami@psy.med.osaka-u.ac.jp.Location evidence
Hirakata, JP · Author affiliation
Department of Psychiatry, Osaka Psychiatric Medical Center, Hirakata, Osaka, Japan.Location evidence
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Original abstract
Behavioral disinhibition is a core feature of behavioral variant frontotemporal dementia (bvFTD) and occurs across related FTD-spectrum presentations. Serotonergic dysfunction may contribute to behavioral dysregulation; therefore, we primarily examined dorsal raphe (DR)-centered midbrain ¹²³I-FP-CIT uptake as an indirect extrastriatal signal that may partly reflect serotonin transporter-related binding. Because striatal dopaminergic circuits support reward learning, behavioral inhibition, and context-dependent behavioral updating, striatal uptake was examined exploratorily. This retrospective exploratory study included 21 patients within the FTD spectrum who underwent Neuropsychiatric Inventory (NPI) assessment, magnetic resonance imaging, and ¹²³I-FP-CIT single-photon emission computed tomography within a 3-month window. The primary outcome was the NPI disinhibition score. DR-centered midbrain and striatal specific uptake ratios (SURs) were calculated using the cerebellum as the reference region. Age- and sex-adjusted quasi-Poisson models with a log link were fitted. DR-centered midbrain SUR was not significantly associated with disinhibition in the primary model (β = -1.027, p = 0.353). In the exploratory model, higher striatal SUR was nominally associated with lower disinhibition scores (β = -0.438, p = 0.022). The negative direction of the striatal association was generally preserved across sensitivity analyses, although nominal significance was not retained in all models. DR-centered midbrain SUR was not significantly associated with behavioral disinhibition in this small FTD-spectrum cohort. Lower striatal SUR showed a directionally consistent but sensitivity-dependent nominal association with greater disinhibition. This hypothesis-generating finding may reflect broader frontostriatal disease burden, striatal neurodegeneration, parkinsonian-spectrum overlap, or partial-volume effects and does not establish a disinhibition-specific dopaminergic mechanism.