D1-Dopamine Receptor Availability in First-Episode Neuroleptic Naive Psychosis Patients

Abstract

Background: Positron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs.

Methods: Here, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390.

Results: We observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum.

Conclusions: This investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.

Keywords: D1 dopamine receptor; dorsolateral prefrontal cortex; drug naïve; positron emission tomography; schizophrenia.

Figure 1.

Standardized residuals representing the difference between healthy controls and psychosis patients after correction for the effect of age. Significant differences were obtained for the dorsolateral prefrontal cortex (DLPFC).

Figure 2.

Standardized effect sizes (Hedges’ G) representing the comparison between patients and controls after accounting for age for all a priori and exploratory analysis regions presented with error bars representing standard errors. ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; MPFC, medial prefrontal cortex; OFC, orbito frontal cortex; STR, striatum; TC, temporal cortex.