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Article / Publication Details
Background/Aims: α-Synuclein (SNCA) may be a key factor in dopaminergic neurotransmission, reward processing, and neurodegeneration in Parkinson’s disease (PD). We investigated delay discounting of reward and caudate volume in SNCA gene duplication carriers before and after the development of PD. Methods: Participants were 7 presymptomatic SNCA duplication carriers who later developed PD (follow-up period: 5.4 years) and 10 matched non-carrier controls. At the follow-up assessment, patients received levodopa (l-DOPA) therapy. Delay discounting of reward was assessed with the Kirby discounting questionnaire. We measured the volume of the caudate nucleus and cerebral cortex using structural MRI and FreeSurfer software. Results: In the presymptomatic stage, carriers showed similar delay discounting and caudate volume to that of non-carrier controls. However, after the development of PD, we observed a significant elevation in delay discounting (impulsive decisions) and reduced caudate volume. There was no cortical atrophy. Conclusion: Impaired reward-related decision making and caudate volume loss are not detectable in the presymptomatic stage in SNCA duplication carriers. These behavioral and neuroanatomical alterations are observed after the development of clinical symptoms when there is extensive neurodegeneration. Study limitations include a small sample size as well as the potential confounding effect of general cognitive decline.
Article / Publication Details
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- Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al: Alpha-synuclein locus triplication causes Parkinson’s disease. Science 2003;302:841.
- Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, et al: Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet 2004;364:1167–1169.
- Ahn TB, Kim SY, Kim JY, Park SS, Lee DS, Min HJ, et al: Alpha-synuclein gene duplication is present in sporadic Parkinson disease. Neurology 2008;70:43–49.
- Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, et al: Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann Neurol 2008;63:743–750.
- Onoda K, Okamoto Y, Kunisato Y, Aoyama S, Shishida K, Okada G, et al: Expanding the clinical phenotype of SNCA duplication carriers. Mov Disord 2009;24:1811–1819.
- Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, et al: Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010;65:66–79.
- Lundblad M, Decressac M, Mattsson B, Björklund A: Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons. Proc Natl Acad Sci USA 2012;109:3213–3219.
- Yavich L, Oksman M, Tanila H, Kerokoski P, Hiltunen M, van Groen T, et al: Locomotor activity and evoked dopamine release are reduced in mice overexpressing A30P-mutated human alpha-synuclein. Neurobiol Dis 2005;20:303–313.
- Oksman M, Tanila H, Yavich L: Brain reward in the absence of alpha-synuclein. Neuroreport 2006;17:1191–1194.
- Kéri S, Moustafa AA, Myers CE, Benedek G, Gluck MA: α-Synuclein gene duplication impairs reward learning. Proc Natl Acad Sci USA 2010;107:15992–15994.
- Kirby KN, Petry NM, Bickel WK: Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. J Exp Psychol Gen 1999;128:78–87.
- Ainslie G: Specious reward: a behavioral theory of impulsiveness and impulse control. Psychol Bull 1975;82:463–496.
- Hoffman WF, Schwartz DL, Huckans MS, McFarland BH, Meiri G, Stevens AA, Mitchell SH: Cortical activation during delay discounting in abstinent methamphetamine dependent individuals. Psychopharmacology (Berl) 2008;201:183–193.
- Marco-Pallarés J, Mohammadi B, Samii A, Münte TF: Brain activations reflect individual discount rates in intertemporal choice. Brain Res 2010;1320:123–129.
- Paloyelis Y, Asherson P, Mehta MA, Faraone SV, Kuntsi J: DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls. Neuropsychopharmacology 2010;35:2414–2426.
- Schweighofer N, Yamaguchi S, Doya K, Yamawaki S: Inter-individual discount factor differences in reward prediction are topographically associated with caudate activation. Exp Brain Res 2011;212:593–601.
- Hughes AJ, Daniel SE, Kilford L, Lees AJ: Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.
- Lang AE, Fahn S: Assessment of Parkinson’s disease; in Munsat TL (ed): Quantification of Neurologic Deficit. Boston, Butterworth-Heinemann. 1989, pp 285–309.
- Hoehn M, Yahr M: Parkinsonism: onset, progression and mortality. Neurology 1967;17:427–442.
- Voon V, Fox SH: Medication-related impulse control and repetitive behaviors in Parkinson disease. Arch Neurol 2007;64:1089–1096.
- Weintraub D, Nirenberg M: Impulse control and related disorders in Parkinson’s disease. Neurodegener Dis DOI: 10.1159/000341996.
- Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
- Green L, Myerson J: A discounting framework for choice with delayed and probabilistic rewards. Psychol Bull 2004;130:769–792.
- Fischl B, Salat DH, van der Kouwe AJ, Makris N, Ségonne F, Quinn BT, Dale AM: Sequence-independent segmentation of magnetic resonance images. Neuroimage 2004;23(suppl 1):S69–S84.
- Segonne F, Dale AM, Busa E, Glessner M, Salat D, Hahn HK, Fischl B: A hybrid approach to the skull stripping problem in MRI. Neuroimage 2004;22:1060–1075.
- Housden CR, O’Sullivan SS, Joyce EM, Lees AJ, Roiser JP: Intact reward learning but elevated delay discounting in Parkinson’s disease patients with impulsive-compulsive spectrum behaviors. Neuropsychopharmacology 2010;35:2155–2164.
- Messina D, Cerasa A, Condino F, Arabia G, Novellino F, Nicoletti G, et al: Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy. Parkinsonism Relat Disord 2011;17:172–176.
- Schrag A, Good CD, Miszkiel K, Morris HR, Mathias CJ, Lees AJ, Quinn NP: Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 2000;54:697–702.
- Paviour DC, Price SL, Jahanshahi M, Lees AJ, Fox NC: Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations. Mov Disord 2006;21:989–996.
- Quattrone A, Nicoletti G, Messina D, Fera F, Condino F, Pugliese P, et al: MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology 2008;246:214–221.
- Lee SH, Kim SS, Tae WS, Lee SY, Choi JW, Koh SB, Kwon DY: Regional volume analysis of the Parkinson disease brain in early disease stage: gray matter, white matter, striatum, and thalamus. AJNR Am J Neuroradiol 2011;32:682–687.
- Ibarretxe-Bilbao N, Tolosa E, Junque C, Marti MJ: MRI and cognitive impairment in Parkinson’s disease. Mov Disord 2009;24 (suppl 2):S748–S753.
- Glenn AL, Raine A, Yaralian PS, Yang Y: Increased volume of the striatum in psychopathic individuals. Biol Psychiatry 2010;67:52–58.
- Voelbel GT, Bates ME, Buckman JF, Pandina G, Hendren RL: Caudate nucleus volume and cognitive performance: are they related in childhood psychopathology? Biol Psychiatry 2006;60:942–950.
- Ersche KD, Barnes A, Jones PS, Morein-Zamir S, Robbins TW, Bullmore ET: Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 2011;134:2013–2024.
- Schultz W: Behavioral theories and the neurophysiology of reward. Annu Rev Psychol 2006;57:87–115.
- Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L: Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 2011;10:1015–1025.
- Hinault MP, Farina-Henriquez-Cuendet A, Goloubinoff P: Molecular chaperone and associated cellular clearance mechanisms against toxic protein conformers in Parkinson’s disease. Neurodegener Dis 2011;8:397–412.
- Kéri S, Nagy H, Myers CE, Benedek G, Shohamy D, Gluck MA: Risk and protective haplotypes of the alpha-synuclein gene associated with Parkinson’s disease differentially affect cognitive sequence learning. Genes Brain Behav 2008;7:31–36.