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.
"ASL perfusion MRI has received considerable attention in clinical neuroscience due to its quantitative and non-invasive nature. Absolute CBF values obtained using ASL in the whole brain and specific brain regions have been shown to be reproducible across time scales of minutes, hours to days (Chen et al., 2011; Jain et al., 2012; Jann et al., 2013; Wu et al., 2011). There is a good correlation between ASL CBF and the gold standard of 15 O-PET in both resting state and activation studies (Feng et al., 2004; Kilroy et al., 2013; Ye et al., 2000). "
"Despite the novelty of the approach, the reliability of the study using perfusion SPECT to explore functional connectivity in depression was reinforced by the large number of investigated subjects and the high statistical reliability of the study since the sampling error decreases with increase of sample size. In the present study, 32% of patients were medicated with various drugs, mainly selective serotonin reuptake inhibitors and anxiolytics, whose use has been reported to decrease CBF (Chen et al., 2011). "
[Show abstract][Hide abstract] ABSTRACT: Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed.
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