(S)-citalopram influences amygdala modulation in healthy subjects: a randomized placebo-controlled double-blind fMRI study using dynamic causal modeling

• DOI: 10.1016/j.neuroimage.2014.12.044
• Publication Date: 2014-12-20T07:40:38Z
• Authors: Ronald Sladky; Marie Spies; Andre Hoffmann; Georg Kranz; Allan Hummer; Gregor Gryglewski; Rupert Lanzenberger; Christian Windisc...; Siegfried Kasper
• Keywords: Adult; Male; Cross-Over Studies; 301401 Brain research; OFC; Citalopram; Amygdala; 301210 Psychopharmakologie; Magnetic Resonance Imaging; Healthy Volunteers; 3. Good health; 03 medical and health sciences; Escitalopram; 0302 clinical medicine; Double-Blind Method; Isomerism; 301210 Psychopharmacology; Dynamic causal modeling; SSRI; Humans; Female; 301401 Hirnforschung; Selective Serotonin Reuptake Inhibitors

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.