Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder

Abstract

The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala.

Trial registration: ClinicalTrials.gov NCT00369915.

Keywords: Amygdala; Functional magnetic resonance imaging (fMRI); Major depressive disorder; Rapid-acting antidepressants; Scopolamine; Stimulus processing.

Figure 1.

Anatomically defined left and right amygdala region of interest (ROI) placement.

Figure 2.

Amygdalar activity and treatment response to scopolamine. Pre-treatment activity during explicit processing of sad faces (AFs) correlated negatively with antidepressant response (percent reduction of symptoms relative to baseline, represented by positive numbers) to scopolamine, r= −.72, p =0.004 in the left amygdala (a) and r= −.55, p=0.04 in the right amygdala (b).

Figure 3.

Baseline amygdalar activity in healthy control subjects (N=14), subjects with major depressive disorder (MDD) who responded to subsequent scopolamine treatment (N=7), and MDD subjects who did not respond to scopolamine treatment (N=7). Treatment responders differed significantly from healthy subjects and treatment non-responders in both the left (p<0.03) and right (p<0.02) amygdala.