title: Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype.
abstract: This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n=11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques.
authors.affiliation: St. Elizabeth's Medical Center, Department of Psychiatry, Boston, MA 02135, USA. mhenry14@partners.org
authors.forename: Michael E
authors.initials: ME
authors.lastname: Henry
authors.forename: Tara L
authors.initials: TL
authors.lastname: Lauriat
authors.forename: Steven B
authors.initials: SB
authors.lastname: Lowen
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Churchill
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005145:Face; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010100:Oxygen; D010597:Pharmacogenetics; D010775:Photic Stimulation; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D010100:Oxygen; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Affective stimulus; Antidepressant; Functional magnetic resonance imaging; Imaging genetics; Pharmaco-fMRI