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Quantification of Cerebral Blood Flow as Biomarker of Drug Effect: Arterial Spin Labeling phMRI After a Single Dose of Oral Citalopram
Author(s) -
Chen Y,
Wan HI,
O'Reardon JP,
Wang DJJ,
Wang Z,
Korczykowski M,
Detre JA
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.296
Subject(s) - cerebral blood flow , orbitofrontal cortex , medicine , citalopram , pharmacology , biomarker , insula , anesthesia , psychology , neuroscience , cardiology , chemistry , antidepressant , hippocampus , prefrontal cortex , biochemistry , cognition
Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood flow (CBF), which can be used as a biomarker of drug effects in pharmacological magnetic resonance imaging (phMRI). In a double‐blind, placebo‐controlled crossover study, we investigated the effects of a single oral dose of citalopram (20 mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support‐vector machine (SVM) analysis detected significant drug‐induced reduction in CBF in brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal cortex. These regions have been shown to have abnormally elevated CBF in patients with major depression, as well as in subjects genetically prone to depression. Mixed‐effects analysis on data extracted from selected regions of interest (ROIs) revealed significant drug effect only in serotonergic areas of the brain ( z = −4.45, P < 0.005). These results demonstrate the utility of ASL phMRI as a biomarker of pharmacological activity of orally administered drugs in the brain. Clinical Pharmacology & Therapeutics (2011) 89 2, 251–258. doi: 10.1038/clpt.2010.296