Abnormal dopamine uptake sites in postmortem striatum from patients with tourette's syndrome
Abstract
The dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre‐ and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites ([3 H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High‐pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4‐dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors ([3 H]SCH 23390 and [3 H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3′,5′‐ monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We spéculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The DA hypothesis of TS was originally proposed nearly 30 years ago and has been corroborated by post-mortem data.
“The DA hypothesis of TS was originally proposed nearly 30 years ago [617], and has been corroborated by post-mortem data [618]”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [618]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
BROWN, B. L., Albano, J. D. M., Ekins, R. P., et al. (1971) · Biochemical Journal · doi:10.1042/bj1210561 · Cited by 1,541 · see citing works
Antischizophrenic Drugs: Chronic Treatment Elevates Dopamine Receptor Binding in Brain
Burt, D. R., Creese, I., & Snyder, S. H. (1977) · Science · doi:10.1126/science.847477 · Cited by 1,027 · see citing works
Billard, W., Ruperto, V., Crosby, G., et al. (1984) · Life Sciences · doi:10.1016/0024-3205(84)90540-x · Cited by 568 · see citing works
Shapiro, E. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810080052006 · Cited by 355 · see citing works
[3H]mazindol binding associated with neuronal dopamine and norepinephrine uptake sites.
Javitch, J. A., Blaustein, R. O., & Snyder, S. H. (1984) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)14974-2 · Cited by 283 · see citing works
Tourette's syndrome and tic disorders : clinical understanding and treatment
Cohen, D. J., BRUUN, R. D., & Leckman, J. F. (1988) · Wiley eBooks · Cited by 263 · see citing works
Javitch, J. A., Strittmatter, S. M., & Snyder, S. H. (1985) · Journal of Neuroscience · doi:10.1523/jneurosci.05-06-01513.1985 · Cited by 244 · see citing works
Tourette Syndrome and Other Tic Disorders Diagnosis, Pathophysiology, and Treatment
Singer, H. S., & Walkup, J. T. (1991) · Medicine · doi:10.1097/00005792-199101000-00002 · Cited by 191 · see citing works
Self-citationBiogenic amine metabolism in tourette syndrome
Butler, I. J., Koslow, S. H., Seifert, W. E., Caprioli, R. M., & Singer, H. S. (1979) · Annals of Neurology · doi:10.1002/ana.410060109 · Cited by 185 · see citing works
Self-citationDopaminergic dysfunction in tourette syndrome
Singer, H. S., Butler, I. J., Tune, L. E., Seifert, W. E., & Coyle, J. T. (1982) · Annals of Neurology · doi:10.1002/ana.410120408 · Cited by 180 · see citing works
Self-citationThe gilles de la tourette syndrome
Robertson, M. (1989) · Behaviour Research and Therapy · doi:10.1016/0005-7967(89)90100-9 · Cited by 176 · see citing works
Gilles de la Tourette syndrome after long‐term chlorpromazine therapy
Klawans, H. L., Falk, D. K., Nausieda, P. A., & Weiner, W. J. (1978) · Neurology · doi:10.1212/wnl.28.10.1064 · Cited by 167 · see citing works
Chronic, Multiple Tics of Gilles de la Tourette's Disease
Cohen, D. J. (1978) · Archives of General Psychiatry · doi:10.1001/archpsyc.1978.01770260123015 · Cited by 147 · see citing works
Effect of tetrabenazine on tics and sleep of Gilles de la Tourette's syndrome
Jankovic, J. J., Glaze, D. G., & Frost, J. D. (1984) · Neurology · doi:10.1212/wnl.34.5.688 · Cited by 130 · see citing works
Tourette's Syndrome and Tic Disorders
Sweet, R. D. (1988) · Neurology · doi:10.1212/wnl.38.12.1902-a · Cited by 105 · see citing works
[3H]mazindol binding associated with neuronal dopamine uptake sites in corpus striatum membranes
Javitch, J. A., Blaustein, R. O., & Snyder, S. H. (1983) · European Journal of Pharmacology · doi:10.1016/0014-2999(83)90574-5 · Cited by 100 · see citing works
Zaczek, R. C., & Coyle, J. T. (1982) · Journal of Neural Transmission · doi:10.1007/bf01243515 · Cited by 91 · see citing works
Janowsky, A. J., Vocci, F. J., Berger, P. A., et al. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb02908.x · Cited by 90 · see citing works
Presynaptic Catecholamine Antagonists as Treatment for Tourette Syndrome
Sweet, R. D. (1974) · Archives of General Psychiatry · doi:10.1001/archpsyc.1974.01760180095012 · Cited by 77 · see citing works
Dopamine Uptake Sites and Dopamine Receptors in Parkinson’s Disease and Schizophrenia
Pearce, R. K. B., Seeman, P. M., Jellinger, K., et al. (2008) · European Neurology · doi:10.1159/000117168 · Cited by 71 · see citing works
Two binding sites for 3H-spiroperidol on rat striatal membranes
Briley, M., & Langer, S. Z. (1978) · European Journal of Pharmacology · doi:10.1016/0014-2999(78)90363-1 · Cited by 66 · see citing works
Tourette's syndrome: A neurochemical analysis of postmortem cortical brain tissue
Singer, H. S., Hahn, I., Krowiak, E. J., Nelson, E., & Moran, T. H. (1990) · Annals of Neurology · doi:10.1002/ana.410270415 · Cited by 65 · see citing works
Self-citationHaloperidol, Fluphenazine and Clonidine in Tourette Syndrome: Controversies in Treatment
Singer, H. S., Gammon, K., & Quaskey, S. A. (2008) · Pediatric Neurosurgery · doi:10.1159/000120222 · Cited by 60 · see citing works
Self-citationChronic L-deprenyl-induced up-regulation of the dopamine uptake carrier
Wiener, H. L., Hashim, A., Lajtha, Á., et al. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90418-4 · Cited by 59 · see citing works
Glynn, G. E., & Yamamoto, B. K. (1989) · Brain Research · doi:10.1016/0006-8993(89)90799-3 · Cited by 39 · see citing works
The Relationship Between Stimulant Medication and Tics
Golden, G. S. (1988) · Pediatric Annals · doi:10.3928/0090-4481-19880601-08 · Cited by 37 · see citing works
Striatal dopamine innervation and receptor density: regional effects of the weaver mutation
Pullara, J. M., & Marshall, J. F. (1989) · Brain Research · doi:10.1016/0006-8993(89)91586-2 · Cited by 30 · see citing works
Neuromodulation and Brain Function
Vizi, E. S. (1985) · Neurochemistry International · doi:10.1016/0197-0186(85)90180-9 · Cited by 23 · see citing works
Desipramine Binding: Relationship to Central and Sympathetic Noradrenergic Activity
Swann, A. C., Duman, R., & Hewitt, L. O. (1985) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1985.tb05455.x · Cited by 17 · see citing works
Insights into the pathophysiology and pathogenesis of Gilles de la Tourette syndrome.
Friedhoff, A. J. (1986) · PubMed · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Frontal-subcortical circuits and human behavior
Cummings, J. L. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540080076020 · Cited by 2,262 · see citing works
the ESSTS Guidelines Group, Roessner, V., Plessen, K. J., Rothenberger, A., Ludolph, A. G., Rizzo, R., Skov, L., Strand, G., Stern, J. S., Termine, C., et al. (2011) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-011-0163-7 · Cited by 461 · see citing works
The Dopamine Transporter and Attention-Deficit/Hyperactivity Disorder
Madras, B. K., Miller, G. M., & Fischman, A. J. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.10.011 · Cited by 393 · see citing works
Dichter, G. S., Damiano, C. A., & Allen, J. A. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-19 · Cited by 299 · see citing works
Elevated Intrasynaptic Dopamine Release in Tourette’s Syndrome Measured by PET
Singer, H. S., Szymanski, S., Giuliano, J., Yokoi, F., Dogan, A. S., Brasic, J. R., Zhou, Y., Grace, A. A., & Wong, D. F. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.8.1329 · Cited by 259 · see citing works
Self-citationWong, D. F., Brašić, J. R., Singer, H. S., Schretlen, D. J., Kuwabara, H., Zhou, Y., Nandi, A., Maris, M. A., Alexander, M., Ye, W., et al. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301528 · Cited by 253 · see citing works
Self-citationWolf, S. S., Jones, D. W., Knable, M. B., Gorey, J. G., Lee, K. S., Hyde, T. M., Coppola, R., & Weinberger, D. R. (1996) · Science · doi:10.1126/science.273.5279.1225 · Cited by 252 · see citing works
Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.
Felling, R. J., & Singer, H. S. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0150-11.2011 · Cited by 227 · see citing works
Self-citationThe placebo effect in neurological disorders
de la Fuente-Fernández, R., Schulzer, M., & Stoessl, A. J. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00038-8 · Cited by 187 · see citing works
Neuromodulation in Tourette syndrome: dopamine and beyond
Buse, J., Schoenefeld, K., Münchau, A., & Roessner, V. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.10.004 · Cited by 185 · see citing works
Increased ventral striatal monoaminergic innervation in Tourette syndrome
Albin, R. L., Koeppe, R. A., Bohnen, N. I., Nichols, T. E., Meyer, P., Wernette, K., Minoshima, S., Kilbourn, M. R., & Frey, K. A. (2003) · Neurology · doi:10.1212/01.wnl.0000076181.39162.fc · Cited by 150 · see citing works
Heterogeneity of obsessive-compulsive disorder: A literature review
Lochner, C., & Stein, D. J. (2003) · Harvard Review of Psychiatry · doi:10.1080/10673220303949 · Cited by 143 · see citing works
NEUROIMAGING AND NEUROPSYCHOLOGY OF THE STRIATUM
Rauch, S. L., & Savage, C. R. (1997) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70343-9 · Cited by 148 · see citing works
Dopamine transporter binding in Gilles de la Tourette syndrome
Müller-Vahl, K. R., Berding, G., Brücke, T., Kolbe, H., Meyer, G. J., Hundeshagen, H., Dengler, R., Knapp, W. H., & Emrich, H. M. (2000) · Journal of Neurology · doi:10.1007/pl00007806 · Cited by 95 · see citing works
STEEVES, T., & FOX, S. (2008) · Progress in Brain Research · doi:10.1016/s0079-6123(08)00924-2 · Cited by 79 · see citing works
Serra‐Mestres, J., Ring, H. A., Costa, D. C., Gacinovic, S., Walker, Z., Lees, A. J., Robertson, M. M., & Trimble, M. R. (2004) · Acta Psychiatrica Scandinavica · doi:10.1111/j.0001-690x.2004.00214.x · Cited by 76 · see citing works
Dopamine Receptor D2 Gene Polymorphisms Are Associated in Taiwanese Children With Tourette Syndrome
Lee, C.-C., Chou, I.-C., Tsai, C.-H., Wang, T.-R., Li, T.-C., & Tsai, F.-J. (2005) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.05.005 · Cited by 63 · see citing works
Stamenkovic, M., Schindler, S. D., Asenbaum, S., Neumeister, A., Willeit, M., Willinger, U., de Zwaan, M., Riederer, F., Aschauer, H. N., & Kasper, S. (2001) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(00)00134-6 · Cited by 52 · see citing works
Yeh, C.-B., Lee, C.-S., Ma, K.-H., Lee, M.-S., Chang, C.-J., & Huang, W.-S. (2007) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2007.01.003 · Cited by 41 · see citing works
Evaluation of Tourette’s syndrome by 99mTc-TRODAT-1 SPECT/CT imaging
Liu, H., Dong, F., Meng, Z., Zhang, B., Tan, J., & Wang, Y. (2010) · Annals of Nuclear Medicine · doi:10.1007/s12149-010-0389-3 · Cited by 34 · see citing works
[99mTc]TRODAT-1/[123I]IBZM SPECT studies of the dopaminergic system in Tourette syndrome
Hwang, W.-J., Yao, W.-J., Fu, Y.-K., & Yang, A.-S. (2008) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2007.04.006 · Cited by 29 · see citing works
Evaluating dopamine transporter activity with 99mTc-TRODAT-1 SPECT in drug-naive Tourette's adults
Yeh, C.-B., Lee, C.-H., Chou, Y.-H., Chang, C.-J., Ma, K.-H., & Huang, W.-S. (2006) · Nuclear Medicine Communications · doi:10.1097/01.mnm.0000239485.53780.16 · Cited by 29 · see citing works
- Authors
- Singer, H. S., Hahn, I., & Moran, T. H.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Singer, Harvey S.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1991-10
- Volume
- 30
- Issue
- 4
- Pages
- 558-562
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2074018083
- Cited by
- 273
- References
- 31
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 9 · 2012: 8
- FWCI
- 16.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01ns027327-01)
- National Institute of Neurological Disorders and Stroke (NS 27327)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- Tourette syndrome, dopamine uptake, striatum, caudate nucleus, putamen, dopamine hypothesis, dopamine receptors, dopamine D1 receptor, dopamine D2 receptor, dopamine metabolism, homovanillic acid, cyclic AMP, antipsychotic drugs, postmortem brain
- MeSH terms
- Adult, Caudate Nucleus, Chromatography, High Pressure Liquid, Corpus Striatum, Dopamine, Female, Tourette Syndrome, Homovanillic Acid, Humans, Kinetics, Male, Middle Aged, Putamen, Radioligand Assay, Receptors, Dopamine, 3,4-Dihydroxyphenylacetic Acid, Receptors, Dopamine D1, Receptors, Dopamine D2, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review