title: Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study.
abstract: OBJECTIVE
  Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected outcome value) and prediction error- (discrepancy between expected and actual outcome) related ventral striatal reactivity, as well as the relationship between these measures.
  
  
  METHODS
  A total of 148 unmedicated individuals with major depressive disorder and 31 healthy comparison individuals recruited for the multisite EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study underwent functional MRI during a well-validated reward task. Region of interest and whole-brain data were examined in the first- (N=78) and second- (N=70) recruited cohorts, as well as the total sample, of depressed individuals, and in healthy individuals.
  
  
  RESULTS
  Healthy, but not depressed, individuals showed a significant inverse relationship between reward expectancy and prediction error-related right ventral striatal reactivity. Across all participants, and in depressed individuals only, greater anhedonia severity was associated with a reduced reward expectancy-prediction error inverse relationship, even after controlling for other symptoms.
  
  
  CONCLUSIONS
  The normal reward expectancy and prediction error-related ventral striatal reactivity inverse relationship concords with conditioning models, predicting a shift in ventral striatal responding from reward outcomes to reward cues. This study shows, for the first time, an absence of this relationship in two cohorts of unmedicated depressed individuals and a moderation of this relationship by anhedonia, suggesting reduced reward-contingency learning with greater anhedonia. These findings help elucidate neural mechanisms of anhedonia, as a step toward identifying potential biosignatures of treatment response.
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Tsafrir
authors.initials: T
authors.lastname: Greenberg
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Henry W
authors.initials: HW
authors.lastname: Chase
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Almeida
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Richelle
authors.initials: R
authors.lastname: Stiffler
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Zevallos
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Haris A
authors.initials: HA
authors.lastname: Aslam
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Thilo
authors.initials: T
authors.lastname: Deckersbach
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weyandt
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Crystal
authors.initials: C
authors.lastname: Cooper
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Marisa
authors.initials: M
authors.lastname: Toups
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carmody
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Benji
authors.initials: B
authors.lastname: Kurian
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Scott
authors.initials: S
authors.lastname: Peltier
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Phillip
authors.initials: P
authors.lastname: Adams
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McGrath
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Myrna
authors.initials: M
authors.lastname: Weissman
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Ramin
authors.initials: R
authors.lastname: Parsey
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.affiliation: From the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; the Department of Psychiatry, Massachusetts General Hospital, Boston; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; Functional MRI Laboratory, University of Michigan, Ann Arbor, Mich.; the Department of Psychiatry, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, New York; the Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, Mich.; and the Departments of Psychiatry and Behavioral Science and Radiology, Stony Brook University, Stony Brook, N.Y.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000328:Adult; D059445:Anhedonia / Q000502:physiology*; D059031:Anticipation, Psychological / Q000502:physiology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011569:Psychiatric Status Rating Scales; D012201:Reward; D066328:Ventral Striatum / Q000503:physiopathology*