title: Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression.
abstract: BACKGROUND
  Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals.
  
  
  METHODS
  In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI.
  
  
  RESULTS
  Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences.
  
  
  CONCLUSIONS
  Small sample size, which warrants replication.
  
  
  CONCLUSIONS
  Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression.
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, MA, USA. Electronic address: pkumar@mclean.harvard.edu.
authors.forename: Poornima
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, USA; Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Slavich
authors.affiliation: Department of Psychology, Harvard University, Cambridge, MA, USA.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Berghorst
authors.affiliation: Department of Psychology, Emory University, Atlanta, GA, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Treadway
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Brooks
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Sunny J
authors.initials: SJ
authors.lastname: Dutra
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA; San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Donovan
authors.affiliation: Department of Family and Child Nursing, University of Washington, WA, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Bleil
authors.affiliation: California National Primate Research Center, University of California, Davis, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Maninger
authors.affiliation: Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, MA, USA. Electronic address: dap@mclean.harvard.edu.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Pizzagalli
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010465:Perception / Q000502:physiology; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D012201:Reward; D013315:Stress, Psychological / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D055815:Young Adult
keywords: Anhedonia; Depression; Life events; Reward processing; Stress; fMRI