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