TY - JOUR
T1 - Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder
T2 - Findings from the EMBARC study
AU - Greenberg, Tsafrir
AU - Chase, Henry W.
AU - Almeida, Jorge R.
AU - Stiffler, Richelle
AU - Zevallos, Carlos R.
AU - Aslam, Haris A.
AU - Deckersbach, Thilo
AU - Weyandt, Sarah
AU - Cooper, Crystal
AU - Toups, Marisa
AU - Carmody, Thomas
AU - Kurian, Benji
AU - Peltier, Scott
AU - Adams, Phillip
AU - McInnis, Melvin G.
AU - Oquendo, Maria A.
AU - McGrath, Patrick J.
AU - Fava, Maurizio
AU - Weissman, Myrna
AU - Parsey, Ramin
AU - Trivedi, Madhukar H.
AU - Phillips, Mary L.
N1 - Publisher Copyright:
© 2015, American Psychiatric Association. All rights reserved.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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. Method: 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.
AB - 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. Method: 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.
UR - http://www.scopus.com/inward/record.url?scp=84941039644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941039644&partnerID=8YFLogxK
U2 - 10.1176/appi.ajp.2015.14050594
DO - 10.1176/appi.ajp.2015.14050594
M3 - Article
C2 - 26183698
AN - SCOPUS:84941039644
SN - 0002-953X
VL - 172
SP - 881
EP - 891
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 9
ER -