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Open Access 01-05-2008 | Parkinson’s Disease and Allied Conditions - Original Article

Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [¹²³I]β-CIT SPECT study

Authors: V. Caretti, D. Stoffers, A. Winogrodzka, I.-U. Isaias, G. Costantino, G. Pezzoli, C. Ferrarese, A. Antonini, E.-Ch. Wolters, J. Booij

Published in: Journal of Neural Transmission | Issue 5/2008

Abstract

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson’s disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [¹²³I]β-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PD_T) and without tremor (PD_WT) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [¹²³I]β-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PD_T than in the PD_WT subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [¹²³I]β-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset.

Antonini A, Tesei S, Zecchinelli A, Barone P, De Gaspari D, Canesi M, Sacilotto G, Meucci N, Mariani C, Pezzoli G (2006) Randomized study of sertraline and low-dose amitriptyline in patients with Parkinson’s disease and depression: effect on quality of life. Mov Disord 21:1119–1122PubMedCrossRef

Barone P, Scarzella L, Marconi R, Antonini A, Morgante L, Bracco F, Zappia M, Musch B (2006) Pramipexole versus sertraline in the treatment of depression in Parkinson’s disease: a national multicenter parallel-group randomized study. J Neurol 253:601–607PubMedCrossRef

Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J (1987) Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol 50:344–346PubMedCrossRef

Birkmayer W, Birkmayer JD (1987) Dopamine action and disorders of neurotransmitter balance. Gerontology 33:168–171PubMed

Birkmayer W, Knoll J, Riederer P, Youdim MB, Hars V, Marton J (1985) Increased life expectancy resulting from addition of l-deprenyl to Madopar treatment in Parkinson’s disease: a long-term study. J Neural Transm 64:113–127PubMedCrossRef

Boja JW, Cadet JL, Kopajtic TA, Lever J, Seltzman HH, Wyrick CD, Lewin AH, Abraham P, Carroll FI (1995) Selective labeling of the dopamine transporter by the high affinity ligand 3 beta-(4-[¹²⁵I]iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester. Mol Pharmacol 47:779–786PubMed

Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, Janssen AG, Wolters EC, van Royen EA (1997a) [¹²³I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 62:133–140PubMed

Booij J, Tissingh G, Winogrodzka A, Boer GJ, Stoof JC, Wolters EC, van Royen EA (1997b) Practical benefit of [¹²³I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson’s disease. Eur J Nucl Med 24:68–71PubMedCrossRef

Bowman WC, Osuide G (1968) Interaction between the effects of tremorine and harmine and of other drugs in chicks. Eur J Pharmacol 3:106–111PubMedCrossRef

Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedCrossRef

Brucke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine H, Podreka I (1993) SPECT imaging of dopamine and serotonin transporters with [¹²³I]beta-CIT. Binding kinetics in the human brain. J Neural Transm Gen Sect 94:137–146PubMedCrossRef

Chaudhuri A (2006) Guillain-Barre syndrome. Lancet 367:472–473PubMedCrossRef

de Rijk MC, Rocca WA, Anderson DW, Melcon MO, Breteler MM, Maraganore DM (1997) A population perspective on diagnostic criteria for Parkinson’s disease. Neurology 48:1277–1281PubMed

De Win MM, Habraken JB, Reneman L, Van den Brink W, Den Heeten GJ, Booij J (2005) Validation of [(¹²³)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 30:996–1005PubMedCrossRef

De Deurwaerdere P, Navailles S, Berg KA, Clarke WP, Spampinato U (2004) Constitutive activity of the serotonin2C receptor inhibits in vivo dopamine release in the rat striatum and nucleus accumbens. J Neurosci 24:3235–3241PubMedCrossRef

DeLong MR (1978) Possible involvement of central pacemakers in clinical disorders of movement. Fed Proc 37:2171–2175PubMed

Di Matteo V, Cacchio M, Di Giulio C, Esposito E (2002) Role of serotonin(2C) receptors in the control of brain dopaminergic function. Pharmacol Biochem Behav 71:727–734PubMedCrossRef

Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: an 11C-WAY 100635 PET study. Neurology 60:601–605PubMed

Farde L, Halldin C, Muller L, Suhara T, Karlsson P, Hall H (1994) PET study of [11C]beta-CIT binding to monoamine transporters in the monkey and human brain. Synapse 16:93–103PubMedCrossRef

Fink KB, Gothert M (2007) 5-HT Receptor Regulation of Neurotransmitter Release. Pharmacol Rev

Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55:259–272PubMedCrossRef

Guttman M, Boileau I, Warsh J, Saint-Cyr JA, Ginovart N, McCluskey T, Houle S, Wilson A, Mundo E, Rusjan P, Meyer J, Kish SJ (2007) Brain serotonin transporter binding in non-depressed patients with Parkinson’s disease. Eur J Neurol 14:523–528PubMedCrossRef

Haapaniemi TH, Ahonen A, Torniainen P, Sotaniemi KA, Myllyla VV (2001) [¹²³I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients. Mov Disord 16:124–130PubMedCrossRef

Headley PM, Lodge D, Duggan AW (1976) Drug-induced rhythmical activity in the inferior olivary complex of the rat. Brain Res 101:461–478PubMedCrossRef

Henderson JM, Carpenter K, Cartwright H, Halliday GM (2000a) Degeneration of the centre median-parafascicular complex in Parkinson’s disease. Ann Neurol 47:345–352PubMedCrossRef

Henderson JM, Carpenter K, Cartwright H, Halliday GM (2000b) Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson’s disease: clinical and therapeutic implications. Brain 123(Pt 7):1410–1421PubMedCrossRef

Hirsch EC, Orieux G, Muriel MP, Francois C, Feger J (2003) Nondopaminergic neurons in Parkinson’s disease. Adv Neurol 91:29–37PubMed

Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ (1992) What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathologic study. Neurology 42:1142–1146PubMed

Innis R, Baldwin R, Sybirska E, Zea Y, Laruelle M, al-Tikriti M, Charney D, Zoghbi S, Smith E, Wisniewski G (1991) Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [¹²³I]CIT. Eur J Pharmacol 200:369–370PubMedCrossRef

Innis RB (1994) Single-photon emission tomography imaging of dopamine terminal innervation: a potential clinical tool in Parkinson’s disease. Eur J Nucl Med 21:1–5PubMedCrossRef

Jacobs BL, Fornal CA (1993) 5-HT and motor control: a hypothesis. Trends Neurosci 16:346–352PubMedCrossRef

Jellinger K (1987) Overview of morphological changes in Parkinson’s disease. Adv Neurol 45:1–18PubMed

Kerenyi L, Ricaurte GA, Schretlen DJ, McCann U, Varga J, Mathews WB, Ravert HT, Dannals RF, Hilton J, Wong DF, Szabo Z (2003) Positron emission tomography of striatal serotonin transporters in Parkinson disease. Arch Neurol 60:1223–1229PubMedCrossRef

Kim SE, Lee WY, Choe YS, Kim JH (1999) SPECT measurement of iodine-123-beta-CIT binding to dopamine and serotonin transporters in Parkinson’s disease: correlation with symptom severity. Neurol Res 21:255–261PubMed

Koller WC, Hubble JP (1990) Levodopa therapy in Parkinson’s disease. Neurology 40:(7)

Kostic VS, Djuricic BM, Covickovic-Sternic N, Bumbasirevic L, Nikolic M, Mrsulja BB (1987) Depression and Parkinson’s disease: possible role of serotonergic mechanisms. J Neurol 234:94–96PubMedCrossRef

Kuhn W, Muller T, Gerlach M, Sofic E, Fuchs G, Heye N, Prautsch R, Przuntek H (1996) Depression in Parkinson’s disease: biogenic amines in CSF of “de novo” patients. J Neural Transm 103:1441–1445PubMedCrossRef

Lamarre Y, Joffroy AJ, Dumont M, De Montigny C, Grou F, Lund JP (1975) Central mechanisms of tremor in some feline and primate models. Can J Neurol Sci 2:227–233PubMed

Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, al-Tikriti MS, Sybirska EH, Zimmermann RC, Wisniewski G, Neumeyer JL, (1993) SPECT imaging of dopamine and serotonin transporters with [¹²³I]beta-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 13:295–309PubMedCrossRef

Laruelle M, Baldwin RM, Innis RB (1994a) SPECT imaging of dopamine and serotonin transporters in nonhuman primate brain. NIDA Res Monogr 138:131–159PubMed

Laruelle M, Wallace E, Seibyl JP, Baldwin RM, Zea-Ponce Y, Zoghbi SS, Neumeyer JL, Charney DS, Hoffer PB, Innis RB (1994b) Graphical, kinetic, and equilibrium analyses of in vivo [¹²³I] beta-CIT binding to dopamine transporters in healthy human subjects. J Cereb Blood Flow Metab 14:982–994PubMed

Limousin P, Speelman JD, Gielen F, Janssens M (1999) Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry 66:289–296PubMedCrossRef

Limousin-Dowsey P, Pollak P, Van Blercom N, Krack P, Benazzouz A, Benabid A (1999) Thalamic subthalamic nucleus and internal pallidum stimulation in Parkinson’s disease. J Neurol 246(Suppl 2):II42–II45PubMedCrossRef

Mossner R, Henneberg A, Schmitt A, Syagailo YV, Grassle M, Hennig T, Simantov R, Gerlach M, Riederer P, Lesch KP (2001) Allelic variation of serotonin transporter expression is associated with depression in Parkinson’s disease. Mol Psychiatry 6:350–352PubMedCrossRef

Murai T, Muller U, Werheid K, Sorger D, Reuter M, Becker T, von Cramon DY, Barthel H (2001) In vivo evidence for differential association of striatal dopamine and midbrain serotonin systems with neuropsychiatric symptoms in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 13:222–228PubMed

Neumeyer JL, Wang SY, Milius RA, Baldwin RM, Zea-Ponce Y, Hoffer PB, Sybirska E, al-Tikriti M, Charney DS, Malison RT, (1991) [¹²³I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane: high-affinity SPECT radiotracer of monoamine reuptake sites in brain. J Med Chem 34:3144–3146PubMedCrossRef

Pirker W, Asenbaum S, Kasper S, Walter H, Angelberger P, Koch G, Pozzera A, Deecke L, Podreka I, Brucke T (1995) beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo. J Neural Transm Gen Sect 100:247–256PubMedCrossRef

Pirker W, Asenbaum S, Hauk M, Kandlhofer S, Tauscher J, Willeit M, Neumeister A, Praschak-Rieder N, Angelberger P, Brucke T (2000) Imaging serotonin and dopamine transporters with ¹²³I-beta-CIT SPECT: binding kinetics and effects of normal aging. J Nucl Med 41:36–44PubMed

Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y (1983) Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 275:321–328PubMedCrossRef

Scheffel U, Lever JR, Abraham P, Parham KR, Mathews WB, Kopajtic T, Carroll FI, Kuhar MJ (1997) N-substituted phenyltropanes as in vivo binding ligands for rapid imaging studies of the dopamine transporter. Synapse 25:345–349PubMedCrossRef

Schnitzler A, Timmermann L, Gross J (2006) Physiological and pathological oscillatory networks in the human motor system. J Physiol Paris 99:3–7PubMedCrossRef

Seibyl JP, Innis R, Early ML, et al (1999) Baseline striatal dopamine transporter uptake measured with [¹²³I]â-CIT SPECT may predict the rate of disease progression in idiopathic Parkinson’s disease. J Nucl Med 40:27

Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, Seibyl JP, Rogers JF (2007) Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [¹²³I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study. J Clin Psychopharmacol 27:71–75PubMedCrossRef

Spiegel J, Hellwig D, Samnick S, Jost W, Mollers MO, Fassbender K, Kirsch CM, Dillmann U (2006) Striatal FP-CIT uptake differs in the subtypes of early Parkinson’s disease. J Neural Transm 114(3):331–335PubMedCrossRef

Timmermann L, Gross J, Dirks M, Volkmann J, Freund HJ, Schnitzler A (2003) The cerebral oscillatory network of parkinsonian resting tremor. Brain 126:199–212PubMedCrossRef

Tissingh G, Bergmans P, Booij J, Winogrodzka A, van Royen EA, Stoof JC, Wolters EC (1998) Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [¹²³I]beta-CIT SPECT. J Neurol 245:14–20PubMedCrossRef

Tong J, Hornykiewicz O, Furukawa Y, Kish SJ (2007) Marked dissociation between high noradrenaline versus low noradrenaline transporter levels in human nucleus accumbens. J Neurochem 102:1691–1702PubMedCrossRef

van Dyck CH, Malison RT, Seibyl JP, Laruelle M, Klumpp H, Zoghbi SS, Baldwin RM, Innis RB (2000) Age-related decline in central serotonin transporter availability with [(¹²³)I]beta-CIT SPECT. Neurobiol Aging 21:497–501PubMedCrossRef

Vermeulen RJ, Wolters EC, Tissingh G, Booij J, Janssen AG, Habraken J, Sokole-Busemann E, Stoof JC, Van Royen EA (1995) Evaluation of [¹²³I] beta-CIT binding with SPECT in controls, early and late Parkinson’s disease. Nucl Med Biol 22:985–991PubMedCrossRef

Visser M, Leentjens AF, Marinus J, Stiggelbout AM, van Hilten JJ (2006) Reliability and validity of the Beck depression inventory in patients with Parkinson’s disease. Mov Disord 21:668–672PubMedCrossRef

Volkmann J, Joliot M, Mogilner A, Ioannides AA, Lado F, Fazzini E, Ribary U, Llinas R (1996) Central motor loop oscillations in parkinsonian resting tremor revealed by magnetoencephalography. Neurology 46:1359–1370PubMed

Wilms H, Sievers J, Deuschl G (1999) Animal models of tremor. Mov Disord 14:557–571PubMedCrossRef

Title: Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study
Authors: V. Caretti
D. Stoffers
A. Winogrodzka
I.-U. Isaias
G. Costantino
G. Pezzoli
C. Ferrarese
A. Antonini
E.-Ch. Wolters
J. Booij
Publication date: 01-05-2008
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 5/2008
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-007-0015-2

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Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [¹²³I]β-CIT SPECT study

Abstract

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Abstract

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