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

MRC Clinical Sciences Centre and Centre for Neuroscience, Faculty of Medicine, Imperial CollegeLondon, UK.
Neurology (Impact Factor: 8.29). 11/2010; 75(21):1920-7. DOI: 10.1212/WNL.0b013e3181feb2ab
Source: PubMed


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

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Available from: David J Brooks, Aug 29, 2015
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    • "Synucleinopathies are characterized by a marked cognitive decline, which has a severe impact on the patient's life quality (Possin et al., 2008). Clinical and imaging studies have linked cognitive decline in Parkinson's disease (PD) and Lewy body dementia (LBD) to the malfunction of hippocampal circuitries (Possin et al., 2008;Politis et al., 2010). The most relevant histopathological hallmark of these two conditions is the aggregation of α-synuclein to form Lewy bodies (Spillantini et al., 1997). "
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    • "In contrast, a 123 I-FP-CIT SPECT study found that depressed patients with Parkinson's disease had lower serotonin transporter availability in the midbrain compared to non-depressed patients (Hesse et al., 2009). PET studies have suggested that depression and depressive symptoms are associated with higher serotonin transporter availability (Boileau et al., 2008; Politis et al., 2010b). The reason for the discrepancy between these SPECT and PET findings is unclear and again could be related to small sample sizes in these studies. "
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    ABSTRACT: Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
    Full-text · Article · Jul 2015 · Brain
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    • "depression, apathy) neuropsychiatric symptoms [4] [5]. More specifically, apathy and impulsivity have been linked to dopaminergic imbalance in the ventral striatum [6] [7] whereas, disruption to serotonergic, noradrenergic and dopaminergic activity in the midbrain nuclei, amygdala and cingulate regions has been implicated depression and anxiety [6] [8]. "
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