Dopamine D1 receptor availability is not associated with delusional ideation measures of psychosis proneness

Granville J Matheson,Pontus Plavén-Sigray,Anaïs Louzolo,Jacqueline Borg,Lars Farde,Predrag Petrovic,Simon Cervenka

doi:10.1016/j.schres.2020.06.001

Granville J Matheson, Pontus Plavén-Sigray + Show 5 more

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https://doi.org/10.1016/j.schres.2020.06.001

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Abstract

The dopamine D1 receptor (D1R) is thought to play a role in psychosis and schizophrenia, however positron emission tomography studies comparing patients and controls have been inconsistent. To circumvent some of the limitations of clinical studies, such as antipsychotic exposure, an alternative approach is to examine subclinical psychotic symptoms within the general population, i.e. psychosis proneness traits. In this study, we investigated whether D1R availability is associated with delusional ideation in healthy controls, in four experiments, using [11C]SCH23390 PET (n = 76) and psychometric questionnaires (n = 217). We performed exploratory analyses, direct self-replication, and confirmatory analyses using Bayesian statistical modelling. Collectively, we found strong evidence that there is little to no linear association between delusional ideation and D1R. If hypothesised changes in D1R in drug-naive psychosis patients can be confirmed, our results suggest that they may either occur at disease onset, or that they are associated with specific aspects of psychosis other than delusional ideation.

Highlights

The dopamine system has been centrally implicated in the pathophysiology of schizophrenia for over fifty years, due primarily to the fact that antipsychotic drugs exert their effect by blocking the D2 dopamine receptor (D2R) (Farde et al, 1988; Kapur and Mamo, 2003; Nordström et al, 1993)
We aimed to investigate the relationship between D1 receptor (D1R) availability and delusional ideation in healthy control subjects using a combination of exploratory and confirmatory analyses, in order to generate and test hypotheses respectively
We created a new scale for measurement of delusional ideation from items of the Temperament and Character Inventory (TCI) questionnaire and validated its psychometric properties

Summary

Introduction

The dopamine system has been centrally implicated in the pathophysiology of schizophrenia for over fifty years, due primarily to the fact that antipsychotic drugs exert their effect by blocking the D2 dopamine receptor (D2R) (Farde et al, 1988; Kapur and Mamo, 2003; Nordström et al, 1993). Increases in presynaptic dopamine synthesis capacity have been observed in individuals at high risk of developing schizophrenia (Howes et al, 2009), with greater levels observed for those individuals who later developed a psychotic disorder compared to those who did not (Howes et al, 2011). These observations suggest that changes in dopamine function are evident prior to the onset of psychosis. The frontal cortex, and the dorsolateral prefrontal cortex (DLPFC) in particular, is thought to be a crucial brain region for understanding the biological underpinnings of schizophrenia symptoms (Callicott et al, 2000; Cannon et al, 2002; Selemon and Goldman-Rakic, 1999; Wagstyl et al, 2016), and further study of the D1R in this region has the potential to provide important insights into the postsynaptic dopaminergic aberrations which may occur in the disorder

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