(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.

Keywords: Amygdala; Citalopram; Dynamic causal modeling; Escitalopram; OFC; SSRI.