Pharmacodynamics of IV Citalopram Using Functional MRI
Although much is known about the role of serotonin (5-HT) in the pathophysiology of depression, little is known about the temporal and regional brain alterations in 5-HT as they relate to the treatment of depression and anxiety. This study aimed to evaluate the acute effects of the selective serotonin reuptake inhibitor (SSRI), citalopram, on neuronal activation elicited during an emotional task using functional MRI (fMRI) in healthy subjects. Eight healthy men completed the double-blind placebo-controlled crossover study of citalopram (20 mg infused over 30 min) and normal saline. Subjects performed the emotional task once before drug/placebo infusion (Faces 1) and twice during drug/placebo infusion, once early in the infusion (Faces 2) and once at the end of infusion (Faces 3).
A main effect of task was found in the L and R amygdala. A cluster in the right amygdala had increased activation for the Faces 2 task during the citalopram infusion, compared to the baseline Faces 1 task. An even greater bilateral amygdala response to citalopram was found at the end of infusion (Faces 3), when the citalopram concentrations approach their maxima, compared to the baseline Faces 1 task. This suggests that acute citalopram administration potentiates the amygdala response to emotional stimuli. An exploratory analysis was done using serotonin transporter genotype as a covariate. S allele carriers (2 s/s and 3 s/l) had a greater baseline amygdala response than l/l (n=3) homozygotes. However l/l homozygotes had a greater response to citalopram, comparing the Faces 3 to the Faces 1 task.
This study generated the first in vivo human data regarding the regional effects of acute intravenous SSRI administration on affective task-related neuronal activation. An understanding of the regional effects of SSRIs may aid in understanding the mechanism by which these agents produce their therapeutic effects. By including 5-HTTLPR genotype in the analyses, we may account for some of the variability in response to citalopram and other SSRIs. These efforts contribute to the identification of biological mechanisms and pathways that mediate response to SSRIs, and contribute to our understanding of individual differences in complex behaviors and vulnerability to psychiatric illnesses.
Advisor:Bruce G. Pollock, MD, PhD; Robert R. Bies, PharmD, PhD; Wen Xie, MD, PhD; Howard J. Aizenstein, MD, PhD; Randall B. Smith, PhD; Ahmad R. Hariri, PhD
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication:04/27/2007