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Quantification of Neuroreceptors in the Living Human Brain: IV. Effect of Aging and Elevations of D 2 -Like Receptors in Schizophrenia and Bipolar Illness
Abstract
In a previous study of 10 drug-naive schizophrenic patients, the density of D 2 dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N-[ 11 C] methylspiperone ([ 11 C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D 2 -like dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging? Are D 2 -like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. D 2 -like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D 2 dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects.
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“There is also evidence that the presence of psychosis may moderate patterns of DA receptor binding. Specifically, striatal D2 receptor signaling seems to be greater in psychotic patients with bipolar disorder [286,287], whereas no differences in D2 availability were found between non-psychotic patients with bipolar disorder and controls [288,289].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [287]
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Metadata
- Authors
- Wong, D. F., Pearlson, G. D., Tune, L. E., Young, L. T., Meltzer, C. C., Dannals, R. F., Ravert, H. T., Reith, J., Kuhar, M. J., & Gjedde, A.
- Affiliations
- Department of Radiology and Radiological Sciences, Division of Nuclear Medicine, Baltimore, Maryland
- Department of Psychiatry, Neuroscience Branch, Baltimore, Maryland
- Bispebjerg Hospital (DK)
- National Institute on Drug Abuse (US)
- Aarhus University Hospital (DK)
- Corresponding author
- Wong, Dean F.
- ORCID
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 1997-03
- Volume
- 17
- Issue
- 3
- Pages
- 331-342
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2036684254
- Cited by
- 118
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 8
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh042821-07, 5r01mh040362-07)
- Centers for Disease Control and Prevention (KO1 MN00723)
- National Institute of Mental Health (R01 MH40362, R01MH42821)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- dopamine D2 receptor, D2-like receptors, schizophrenia, aging, receptor density, caudate nucleus, positron emission tomography, receptor quantification, drug-naive patients, psychosis
- MeSH terms
- Adult, Aged, Aging, Basal Ganglia, Bipolar Disorder, Brain Chemistry, Caudate Nucleus, Chromatography, High Pressure Liquid, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Schizophrenia, Spiperone, Tomography, Emission-Computed, Receptors, Dopamine D2, Dopamine Agonists
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