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Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia
Abstract
Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
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“Furthermore, in line with the effects of chronic stress, dopamine activity in the prefrontal cortex appears to be reduced in individuals with a schizophrenia diagnosis [132-134] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [133]
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- Kraepelin, E., Barclay, R. M. & Robertson, G. M. Dementia Præcox and Paraphrenia (E. & S. Livingstone, Edinburgh, 1919).
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The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway
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Metadata
- Authors
- Meyer-Lindenberg, A., Miletich, R. S., Kohn, P. D., Esposito, G., Carson, R. E., Quarantelli, M., Weinberger, D. R., & Berman, K. F.
- Affiliations
- National Institutes of Health (US)
- Venue
- Nature Neuroscience
- Published
- 2002-01-28
- Volume
- 5
- Issue
- 3
- Pages
- 267-271
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2004729128
- Cited by
- 652
- References
- 50
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13 · 2023: 9 · 2022: 15 · 2021: 30 · 2020: 16 · 2019: 32 · 2018: 20 · 2017: 25 · 2016: 31 · 2015: 41 · 2014: 35 · 2013: 38 · 2012: 40
- FWCI
- 19.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- schizophrenia, prefrontal cortex, striatum, dopamine signaling, dopamine uptake, regional cerebral blood flow, Wisconsin Card Sorting Test, prefrontal cortex activation
- MeSH terms
- Cerebrovascular Circulation, Corpus Striatum, Dihydroxyphenylalanine, Dopamine, Fluorine Radioisotopes, Humans, Neuropsychological Tests, Schizophrenia, Statistics as Topic, Synapses, Tomography, Emission-Computed, Prefrontal Cortex
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