Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET
Open accessAbstract
Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis comes from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R). D2R is expressed most highly in the striatum, but most of the recent positron emission tomography (PET) studies have failed to show any change in D2R densities in the striatum of schizophrenics, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex, has been implicated in the control of working memory, and working memory dysfunction is a prominent feature of schizophrenia. We have therefore used PET to examine the distribution of D1R and D2R in brains of drug-naive or drug-free schizophrenic patients. Although no differences were observed in the striatum relative to control subjects, binding of radioligand to D1R was reduced in the prefrontal cortex of schizophrenics. This reduction was related to the severity of the negative symptoms (for instance, emotional withdrawal) and to poor performance in the Wisconsin Card Sorting Test. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.
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Working memory performance in psychotic and healthy subjects relies on dopamine levels within the prefrontal cortex.
“Studies have shown that WM performance in psychotic and healthy subjects rely on dopamine levels within the PFC (Dumontheil et al., 2011; Mattay et al., 2003; Okubo et al., 1997).”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as Okubo et al., 1997
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- Authors
- Okubo, Y., Suhara, T., Suzuki, K., Kobayashi, K., Inoue, O., Terasaki, O., Someya, Y., Sassa, T., Sudo, Y., Matsushima, E., Iyo, M., Tateno, Y., & Toru, M.
- Affiliations
- Tokyo Medical and Dental University (JP)
- National Institute of Radiological Sciences (JP)
- Venue
- Nature
- Published
- 1997-02
- Volume
- 385
- Issue
- 6617
- Pages
- 634-636
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2077767624
- Cited by
- 710
- References
- 1
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 9 · 2023: 9 · 2022: 12 · 2021: 12 · 2020: 20 · 2019: 11 · 2018: 18 · 2017: 20 · 2016: 21 · 2015: 27 · 2014: 29 · 2013: 26 · 2012: 34
- FWCI
- 29.06
- Type
- journal article
- Language
- en
- Open access
- green
- repo.qst.go.jp
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
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- RePEc: Research Papers in Economics (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion)
- 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, dopamine D1 receptor, dopamine D2 receptor, prefrontal cortex, striatum, negative symptoms, working memory, cognitive impairment, radioligand binding, Wisconsin Card Sorting Test, emotional withdrawal
- MeSH terms
- Adult, Cerebral Cortex, Humans, Male, Schizophrenia, Tomography, Emission-Computed, Prefrontal Cortex, Receptors, Dopamine D1, Receptors, Dopamine D2
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