Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET

Yoshiro Okubo, Tetsuya Suhara, Kazutoshi Suzuki, Kaoru Kobayashi, Osamu Inoue, Omi Terasaki, Yasuhiro Someya, Takeshi Sassa, Yasuhiko Sudo, Eisuke Matsushima, Masaomi Iyo, Yukio Tateno and Michio Toru
Additional contact information
Yoshiro Okubo: Tokyo Medical and Dental University School of Medicine
Tetsuya Suhara: National Institute of Radiological Sciences
Kazutoshi Suzuki: National Institute of Radiological Sciences
Kaoru Kobayashi: National Institute of Radiological Sciences
Osamu Inoue: National Institute of Radiological Sciences
Omi Terasaki: Tokyo Medical and Dental University School of Medicine
Yasuhiro Someya: Tokyo Medical and Dental University School of Medicine
Takeshi Sassa: Tokyo Medical and Dental University School of Medicine
Yasuhiko Sudo: National Institute of Radiological Sciences
Eisuke Matsushima: Tokyo Medical and Dental University School of Medicine
Masaomi Iyo: National Institute of Radiological Sciences
Yukio Tateno: National Institute of Radiological Sciences
Michio Toru: Tokyo Medical and Dental University School of Medicine

Nature, 1997, vol. 385, issue 6617, 634-636

Abstract: Abstract Schizophrenia is believed to involve altered activation of dopamine receptors, and support for this hypothesis conies from the antipsychotic effect of antagonists of the dopamine D2 receptor (D2R)1. 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 schizophrenics2–5, raising the possibility that other receptors may also be involved. In particular, the dopamine D1 receptor (D1R), which is highly expressed in the prefrontal cortex6, has been implicated in the control of working memory7,8, and working memory dysfunction is a prominent feature of schizophrenia9. 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 Test10. We propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia.

Date: 1997
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DOI: 10.1038/385634a0

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