Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET

Note: One person sent me a note that they thought that this type of research was of no value because the people they studies had already been subjected to medications that they felt could cause the damage that the researchers were finding in their scans - however, please note that in the text of this report they state they evaluated only "brains of drug-naive or drug-free schizophrenic patients." - Brian.

SCHIZOPHRENIA For many years, schizophrenia was thought to be associated with increased activity of the D2 class of dopamine receptors in the prefrontal cortex of the brain. But thinking is increasingly moving towards the involvement of a more sophisticated network of receptors - and new studies indicate that reduced levels of the D1 class of dopamine receptors are found in the brains of schizophrenics. Eric J. Nestler An emerging pathophysiology Nature 385, 578-579 (1997)

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.

The authors 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. They propose that dysfunction of D1R signalling in the prefrontal cortex may contribute to the negative symptoms and cognitive deficits seen in schizophrenia. Y Okubo, T Suhara, K Suzuki, K Kobayashi, O Inoue, O Terasaki, Y Someya, T Sassa, Y Sudo,E Matsushima, M Iyo, Y Tateno & M Toru Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385, 634 (1997)

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