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Increased cerebral blood flow after single dose of antipsychotics in healthy volunteers depends on dopamine D2 receptor density profiles

Research output: Contribution to journalArticle

Pierluigi Selvaggi, Peter C.T. Hawkins, Ottavia Dipasquale, Gaia Rizzo, Alessandro Bertolino, Juergen Dukart, Fabio Sambataro, Giulio Pergola, Steven C.R. Williams, Federico Turkheimer, Fernando Zelaya, Mattia Veronese, Mitul A. Mehta

Original languageEnglish
Pages (from-to)774-784
JournalNeuroImage
Volume188
Early online date13 Dec 2018
DOIs
Publication statusE-pub ahead of print - 13 Dec 2018

King's Authors

Abstract

As a result of neuro-vascular coupling, the functional effects of antipsychotics in human brain have been investigated in both healthy and clinical populations using haemodynamic markers such as regional Cerebral Blood Flow (rCBF). However, the relationship between observed haemodynamic effects and the pharmacological action of these drugs has not been fully established. Here, we analysed Arterial Spin Labelling (ASL) rCBF data from a placebo-controlled study in healthy volunteers, who received a single dose of three different D2 receptor (D2R) antagonists and tested the association of the main effects of the drugs on rCBF against normative population maps of D2R protein density and gene-expression data. In particular, we correlated CBF changes after antipsychotic administration with non-displaceable binding potential (BPND) template maps of the high affinity D2-antagonist Positron Emission Tomography (PET) ligand [18F]Fallypride and with brain post-mortem microarray mRNA expression data for the DRD2 gene from the Allen Human Brain Atlas (ABA). For all antipsychotics, rCBF changes were directly proportional to brain D2R densities and DRD2 mRNA expression measures, although PET BPND spatial profiles explained more variance as compared with mRNA profiles (PET R2 range = 0.20–0.60, mRNA PET R2 range 0.04–0.20, pairwise-comparisons all pcorrected

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