title: 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.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: szczepaj@mail.nih.gov.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanik
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.affiliation: Janssen Pharmaceuticals, LLC of Johnson and Johnson, Inc., Titusville, NJ, USA.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: Physical Medicine and Rehabilitation, Jewish Medical Center, Brooklyn Hospital Center, Brooklyn, NY, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA; Neuroscience Biomarkers Division, Janssen Research and Development, San Diego, CA, USA.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Furey
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D015415:Biomarkers; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D005149:Facial Expression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D018727:Muscarinic Antagonists; D012601:Scopolamine
keywords: Amygdala; Functional magnetic resonance imaging (fMRI); Major depressive disorder; Rapid-acting antidepressants; Scopolamine; Stimulus processing