title: (S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling.
abstract: Citalopram and Escitalopram are gold standard pharmaceutical treatment options for affective, anxiety, and other psychiatric disorders. However, their neurophysiologic function on cortico-limbic circuits is incompletely characterized. Here we studied the neuropharmacological influence of Citalopram and Escitalopram on cortico-limbic regulatory processes by assessing the effective connectivity between orbitofrontal cortex (OFC) and amygdala using dynamic causal modeling (DCM) applied to functional MRI data. We investigated a cohort of 15 healthy subjects in a randomized, crossover, double-blind design after 10days of Escitalopram (10mg/d (S)-citalopram), Citalopram (10mg/d (S)-citalopram and 10mg/d (R)-citalopram), or placebo. Subjects performed an emotional face discrimination task, while undergoing functional magnetic resonance imaging (fMRI) scanning at 3 Tesla. As hypothesized, the OFC, in the context of the emotional face discrimination task, exhibited a down-regulatory effect on amygdala activation. This modulatory effect was significantly increased by (S)-citalopram, but not (R)-citalopram. For the first time, this study shows that (1) the differential effects of the two enantiomers (S)- and (R)-citalopram on cortico-limbic connections can be demonstrated by modeling effective connectivity methods, and (2) one of their mechanisms can be linked to an increased inhibition of amygdala activation by the orbitofrontal cortex.
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sladky
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Marie
authors.initials: M
authors.lastname: Spies
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Andre
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Kranz
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Allan
authors.initials: A
authors.lastname: Hummer
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gryglewski
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.affiliation: MR Center of Excellence, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Windischberger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: sci-biolpsy@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
mesh_terms: D000328:Adult; D000679:Amygdala / Q000187:drug effects*; D015283:Citalopram / Q000737:chemistry* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007536:Isomerism; D008279:Magnetic Resonance Imaging; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Amygdala; Citalopram; Dynamic causal modeling; Escitalopram; OFC; SSRI