title: The Effect of Mineralocorticoid and Glucocorticoid Receptor Antagonism on Autobiographical Memory Recall and Amygdala Response to Implicit Emotional Stimuli.
abstract: BACKGROUND
  Acutely elevated cortisol levels in healthy humans impair autobiographical memory recall and alter hemodynamic responses of the amygdala to emotionally valenced stimuli. It is hypothesized that the effects of the cortisol on cognition are influenced by the ratio of mineralocorticoid receptor to glucocorticoid receptor occupation. The current study examined the effects of acutely blocking mineralocorticoid receptors and glucocorticoid receptors separately on 2 processes known to be affected by altering levels of cortisol: the specificity of autobiographical memory recall, and the amygdala hemodynamic response to sad and happy faces.
  
  
  METHODS
  We employed a within-subjects design in which 10 healthy male participants received placebo, the mineralocorticoid receptor antagonist spironolactone (600mg) alone, and the glucocorticoid receptor antagonist mifepristone (600mg) alone in a randomized, counter-balanced order separated by 1-week drug-free periods.
  
  
  RESULTS
  On autobiographical memory testing, mineralocorticoid receptor antagonism impaired, while glucocorticoid receptor antagonism improved, recall relative to placebo, as evinced by changes in the percent of specific memories recalled. During fMRI, the amygdala hemodynamic response to masked sad faces was greater under both mineralocorticoid receptor and glucocorticoid receptor antagonism relative to placebo, while the response to masked happy faces was attenuated only during mineralocorticoid receptor antagonism relative to placebo.
  
  
  CONCLUSIONS
  These data suggest both mineralocorticoid receptor and glucocorticoid receptor antagonism (and potentially any deviation from the normal physiological mineralocorticoid receptor/glucocorticoid receptor ratio achieved under the circadian pattern) enhances amygdala-based processing of sad stimuli and may shift the emotional processing bias away from the normative processing bias and towards the negative valence. In contrast, autobiographical memory was enhanced by conditions of reduced glucocorticoid receptor occupancy.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets). youngk@pitt.edu.
authors.forename: Kymberly D
authors.initials: KD
authors.lastname: Young
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets).
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets).
authors.forename: Teresa
authors.initials: T
authors.lastname: Victor
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets).
authors.forename: Masaya
authors.initials: M
authors.lastname: Misaki
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets).
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bodurka
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA (Dr Young) Laureate Institute for Brain Research, Tulsa, OK (Drs Young, Preskorn, Victor, Misaki, Bodurka, and Drevets); Kansas University School of Medicine, Wichita, KS (Dr Preskorn); Biomedical Engineering Center, University of Oklahoma College of Engineering, Norman, OK (Dr Bodurka); Janssen Research and Development, LLC, of Johnson & Johnson, Inc., New Brunswick, NJ (Dr Drevets).
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
keywords: amygdala; autobiographical memory; cortisol; glucocorticoid; mineralocorticoid