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November 23, 2010; 75 (21) Articles

Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures

M. Politis, K. Wu, C. Loane, F.E. Turkheimer, S. Molloy, D.J. Brooks and P. Piccini
First published November 22, 2010, DOI: https://doi.org/10.1212/WNL.0b013e3181feb2ab
M. Politis
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K. Wu
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C. Loane
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F.E. Turkheimer
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S. Molloy
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D.J. Brooks
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P. Piccini
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Citation
Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures
M. Politis, K. Wu, C. Loane, F.E. Turkheimer, S. Molloy, D.J. Brooks, P. Piccini
Neurology Nov 2010, 75 (21) 1920-1927; DOI: 10.1212/WNL.0b013e3181feb2ab

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Abstract

Background: Depression associated with Parkinson disease (PD) has a different symptom profile to endogenous depression. The etiology of depression in PD remains uncertain though abnormal serotonergic neurotransmission could play a role.

Objective: To assess with PET serotonergic function via in vivo serotonin transporter (5-HTT) availability in antidepressant-naive patients with PD.

Methods: Thirty-four patients with PD and 10 healthy matched control subjects had a clinical battery of tests including the patient-report Beck Depression Inventory–II (BDI-II), the clinician-report Hamilton Rating Scale for Depression (HRSD), and the structured clinical interview for DSM-IV Axis I Disorders (SCID-I). They underwent 11C-DASB PET, a selective in vivo marker of 5-HTT binding in humans.

Results: BDI-II scores correlated with HRSD scores. Ten of 34 patients with PD (29.4%) had BDI-II and HRSD scores above the discriminative cutoff for PD depression though only half of these patients could be classed on SCID-I criteria as having an anxiety/mood disorder. Patients with PD with the highest scores for depression symptoms showed significantly raised 11C-DASB binding in amygdala, hypothalamus, caudal raphe nuclei, and posterior cingulate cortex compared to low score cases, while 11C-DASB binding values in other regions were similarly decreased in depressed and nondepressed patients with PD compared to healthy controls.

Conclusion: Depressive symptoms in antidepressant-naive patients with PD correlate with relatively higher 5-HTT binding in raphe nuclei and limbic structures possibly reflecting lower extracellular serotonin levels. Our data are compatible with a key role of abnormal serotonergic neurotransmission contributing to the pathophysiology of PD depression and justify the use of agents acting on 5-HTT.

Footnotes

  • Study funding: Supported by the Michael J. Fox Foundation (P14104) and the Medical Research Council, UK (Clinical Sciences Center, Neurology group core grant, 2007–2010).

  • ACC
    anterior cingulate cortex
    BDI-II
    Beck Depression Inventory II
    BPND
    binding potential of the specifically bound radioligand relative to the nondisplaceable radioligand in tissue
    DSM-IV
    Diagnostic and Statistical Manual of Mental Disorders, 4th edition
    FOV
    field of view
    H&Y
    Hoehn & Yahr staging
    HRSD
    Hamilton Rating Scale for Depression
    LED
    levodopa equivalent dose
    MMSE
    Mini-Mental State Examination
    PCC
    posterior cingulate cortex
    PD
    Parkinson disease
    PFC
    prefrontal cortex
    ROI
    region of interest
    SCID-I
    structured clinical interview for DSM-IV Axis I Disorders
    SERT/5-HTT
    serotonin transporter
    SSRI
    selective serotonin reuptake inhibitor
    TAC
    time-activity curves
    TCA
    tricyclic antidepressant
    UPDRS
    Unified Parkinson's Disease Rating Scale
    VDR
    volume of distribution ratio

  • Received March 31, 2010.
  • Accepted August 12, 2010.
  • Copyright © 2010 by AAN Enterprises, Inc.
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