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.
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.
Authors: Victoria B Gradin; Poornima Kumar; Gordon Waiter; Trevor Ahearn; Catriona Stickle; Marteen Milders; Ian Reid; Jeremy Hall; J Douglas Steele Journal: Brain Date: 2011-04-10 Impact factor: 13.501
Authors: Jennifer Keller; Christina B Young; Elizabeth Kelley; Katherine Prater; Daniel J Levitin; Vinod Menon Journal: J Psychiatr Res Date: 2013-06-19 Impact factor: 4.791
Authors: Henry W Chase; Robin Nusslock; Jorge Rc Almeida; Erika E Forbes; Edmund J LaBarbara; Mary L Phillips Journal: Bipolar Disord Date: 2013-10-21 Impact factor: 6.744
Authors: A Manelis; C D Ladouceur; S Graur; K Monk; L K Bonar; M B Hickey; A C Dwojak; D Axelson; B I Goldstein; T R Goldstein; G Bebko; M A Bertocci; M K Gill; B Birmaher; M L Phillips Journal: Psychol Med Date: 2015-09-16 Impact factor: 7.723
Authors: Kailyn A L Bradley; Julia A C Case; Rachel D Freed; Emily R Stern; Vilma Gabbay Journal: J Affect Disord Date: 2016-12-01 Impact factor: 4.839
Authors: Bharathi S Gadad; Manish K Jha; Andrew Czysz; Jennifer L Furman; Taryn L Mayes; Michael P Emslie; Madhukar H Trivedi Journal: J Affect Disord Date: 2017-07-05 Impact factor: 4.839
Authors: Matthias Kirschner; Oliver M Hager; Larissa Muff; Martin Bischof; Matthias N Hartmann-Riemer; Agne Kluge; Benedikt Habermeyer; Erich Seifritz; Philippe N Tobler; Stefan Kaiser Journal: Schizophr Bull Date: 2018-01-13 Impact factor: 9.306
Authors: Jean-Philippe Fortin; Nicholas Cullen; Yvette I Sheline; Warren D Taylor; Irem Aselcioglu; Philip A Cook; Phil Adams; Crystal Cooper; Maurizio Fava; Patrick J McGrath; Melvin McInnis; Mary L Phillips; Madhukar H Trivedi; Myrna M Weissman; Russell T Shinohara Journal: Neuroimage Date: 2017-11-17 Impact factor: 6.556
Authors: Alexis E Whitton; Jenna M Reinen; Mark Slifstein; Yuen-Siang Ang; Patrick J McGrath; Dan V Iosifescu; Anissa Abi-Dargham; Diego A Pizzagalli; Franklin R Schneier Journal: Brain Date: 2020-02-01 Impact factor: 13.501