Serotonin transporter binding and anxiety symptoms in Parkinson's disease

BACKGROUND: Anxiety is a common neuropsychiatric symptom in Parkinson's disease (PD), yet the neural mechanisms have been scarcely investigated. Disturbances in dopaminergic and serotonergic signalling may play a role in its pathophysiology. 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) is a single-photon emission CT radiotracer, and its binding in striatal and extrastriatal subcortical brain areas represents predominant binding to the presynaptic dopamine transporter (DAT) and the serotonin transporter (SERT), respectively. Availability of DAT and SERT may thus provide an in vivo measure for the integrity of both dopamine and serotonin neurons. METHODS: We studied the association between anxiety symptoms, measured with an affective subscale of the Beck Anxiety Inventory, and (extra)striatal 123I-FP-CIT binding in 127 non-demented patients with PD with a median disease duration of 2.55 (IQR 2.90) years. We conducted the analyses on patients currently on or not on dopamine replacement therapy (DRT). RESULTS: Severity of anxiety symptoms showed a significant negative association with 123I-FP-CIT binding ratios in the right thalamus (β=-0.203, p=0.019; ΔR2=0.040) (multiple testing pcorr <0.020). In the subgroup of patients not on DRT (n=81), we found a significant negative association between anxiety and thalamic 123I-FP-CIT binding ratios bilaterally (right: β=-0.349, p=0.001, ΔR2=0.119; left: β=-0.269, p=0.017, ΔR2=0.071) (pcorr <0.020). CONCLUSION: This study shows that higher levels of anxiety in patients with PD are associated with lower thalamic 123I-FP-CIT binding, pointing towards a contribution of serotonergic degeneration to anxiety symptoms in PD

Analysis of Extrastriatal I-123-FP-CIT Binding Contributes to the Differential Diagnosis of Parkinsonian Diseases

I-123-N-omega-fluoropropyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl) nortropane (I-123-FP-CIT) SPECT can visualize and quantify striatal dopamine transporter (DAT) binding in vivo. In addition, I-123-FP-CIT has modest affinity for the serotonin transporter (SERT), predominantly represented in extrastriatal binding. On the basis of previous imaging studies that have suggested more pronounced degeneration of other monoaminergic systems in multiple-system atrophy (MSA) and progressive supranuclear palsy (PSP) than in Parkinson disease (PD), we hypothesized that, in addition to striatal DAT binding, there would be differences in extrastriatal I-123-FP-CIT SPECT binding to SERT between MSA, PSP, and PD. Methods: We included patients with parkinsonian type MSA (multiple-system atrophy with predominantly parkinsonism [MSA-P], n - 9), cerebellar type MSA (MSA-C, n = 7), PSP (n = 13), and PD (n = 30). I-123-FP-CIT binding was analyzed using region-of-interest (ROI)-as well as voxel-based methods in both the DAT-rich striatum (caudate nucleus and putamen) and the SERT-rich extrastriatal brain regions (thalamus, hypothalamus, and pons). For SERT analysis, patients on selective serotonin reuptake inhibitor were excluded (n = 48 remained). Results: In the ROI analyses, extrastriatal I-123-FP-CIT binding ratios in the hypothalamus were significantly lower in PSP than in MSA-C patients, and we observed significantly lower striatal I-123-FP-CIT binding ratios in the caudate nucleus of PSP patients than in that of both PD and MSA-C patients. In the posterior putamen, binding ratios were significantly lower in MSA-P, PSP, and PD than MSA-C patients. Striatal ROI outcomes were confirmed by the voxel-based analyses that additionally showed a significantly lower hypothalamic binding in PSP and MSA-P than PD. Conclusion: Striatal I-123-FP-CIT binding to DAT and hypothalamic I-123-FP-CIT binding to SERT are significantly lower in MSA-P and PSP than in PD and MSA-C patients and might therefore be of interest for differential diagnosi

Lower 123I-FP-CIT binding to the striatal dopamine transporter, but not to the extrastriatal serotonin transporter, in Parkinson's disease compared with dementia with Lewy bodies

In this retrospective cross-sectional study we compared 123I‑N‑ω‑fluoropropyl‑2β‑carbomethoxy‑3β‑(4‑iodophenyl)nortropane (123I-FP-CIT) binding to the striatal dopamine and the extrastriatal serotonin transporter (DAT and SERT, respectively) between Parkinson's disease (PD) and dementia with Lewy bodies (DLB) to gain more insight in the pathophysiology of the two diseases.We compared 123I-FP-CIT single photon emission computed tomography scans of, age-, gender matched patients with cognitive decline in same range of severity with PD (n = 53) or DLB (n = 53) using a regions of interest (ROIs) approach. We derived ROIs anatomically from individual magnetic resonance imaging brain scans. To corroborate the ROI findings, we performed additional whole-brain voxel-based analyses.In both ROI and voxel-based analyses, 123I-FP-CIT binding in PD patients was significantly lower in the bilateral posterior putamen than in DLB patients (left: F(1,103) = 18.363, P < 0.001, ω2 = 0.14; right: F(1,103) = 20.434, P < 0.001, ω2 = 0.15) (Pcorr < 0.033). Caudate/putamen ratios were also significantly lower in DLB than in PD (U(105) = 724.0, P < 0.001). Extrastriatal SERT binding showed no difference between PD and DLB.These results suggest similar involvement of serotonergic structures in the degenerative process in PD and DLB. Keywords: Parkinson's disease, Dementia with Lewy bodies, 123I-FP-CIT, SERT, DA

Striatal DAT and extrastriatal SERT binding in early-stage Parkinson's disease and dementia with Lewy bodies, compared with healthy controls: An 123I-FP-CIT SPECT study

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are thought to be part of a spectrum: both have a clinical profile including symptoms associated with dopaminergic and serotonergic loss, yet few imaging studies have focused on serotonergic neurodegeneration in both disorders. We aimed to study degeneration of terminals with dopamine and serotonin transporter (DAT and SERT, respectively) in patients with early-stage PD and DLB relative to healthy controls, using 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ( 123 I-FP-CIT) single photon emission computed tomography (SPECT). We conducted region of interest (ROI) and voxel-based analyses on 123 I-FP-CIT SPECT scans. Using the cerebellum as a reference region, we determined binding ratios (BRs) for bilateral ROIs in the DAT-rich striatum (head of the caudate nucleus and posterior putamen) and SERT-rich extrastriatal brain regions (thalamus, hypothalamus and hippocampus). We compared BRs in PD and DLB patients with BRs in healthy controls (all groups: n = 16). Both PD and DLB patients had lower striatal 123 I-FP-CIT BRs than healthy controls for the bilateral caudate head (PD—left: F(1,29) = 28.778, P <.001, ω 2 = 0.35; right: F(1,29) = 35.338, P <.001, ω 2 = 0.42; DLB—left: F(1,29) = 28.241, P <.001, ω 2 = 0.31; right: F(1,29) = 18.811, P <.001, ω 2 = 0.26) and bilateral posterior putamen (PD—left: F(1,29) = 107.531, P <.001, ω 2 = 0.77; right: F(1,29) = 87.525, P <.001, ω 2 = 0.72; DLB—left: F(1,29) = 39.910, P <.001, ω 2 = 0.48; right: F(1,29) = 26.882, P <.001, ω 2 = 0.38). DLB patients had lower hypothalamic 123 I-FP-CIT BRs than healthy controls (F(1,29) = 6.059, P =.020, ω 2 = 0.12). In the voxel-based analysis, PD and DLB patients had significantly lower striatal binding than healthy controls. Both PD patients in the early disease stages and DLB patients have reduced availability of striatal DAT, and DLB patients lower hypothalamic SERT compared with healthy controls. These observations add to the growing body of evidence that PD and DLB are not merely dopaminergic diseases, thereby providing additional clinicopathological insights