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

• Published in: NeuroImage (Orlando, Fla.) Vol. 108; pp. 243 - 250
• Main Authors: Sladky, Ronald, Spies, Marie, Hoffmann, Andre, Kranz, Georg, Hummer, Allan, Gryglewski, Gregor, Lanzenberger, Rupert, Windischberger, Christian, Kasper, Siegfried
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2015; Elsevier Limited
• Subjects: Activation; Adult; Amygdala; Amygdala - drug effects; Antidepressants; Anxiety; Citalopram; Citalopram - chemistry; Citalopram - pharmacology; Cortexes; Cross-Over Studies; Crossovers; Discrimination; Double-Blind Method; Dynamic causal modeling; Dynamic tests; Dynamics; Escitalopram; Female; Grants; Healthy Volunteers; Humans; Influence; Isomerism; Magnetic Resonance Imaging; Male; Medical imaging; Neurobiology; OFC; Serotonin; Serotonin Uptake Inhibitors - chemistry; Serotonin Uptake Inhibitors - pharmacology; SSRI; Studies; Tasks; SSRI; Dynamic causal modeling; Amygdala; Escitalopram; OFC; Citalopram
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2014.12.044

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.