Reward Behavior Disengagement, a Neuroeconomic Model-Based Objective Measure of Reward Pathology in Depression: Findings from the EMBARC Trial

Author:

Giles Michael A.1ORCID,Cooper Crystal M.23,Jha Manish K.2ORCID,Chin Fatt Cherise R.2,Pizzagalli Diego A.45,Mayes Taryn L.2ORCID,Webb Christian A.45,Greer Tracy L.26,Etkin Amit7,Trombello Joseph M.2,Chase Henry W.8,Phillips Mary L.8,McInnis Melvin G.9,Carmody Thomas10,Adams Phillip11,Parsey Ramin V.12,McGrath Patrick J.11,Weissman Myrna11,Kurian Benji T.1,Fava Maurizio413,Trivedi Madhukar H.2

Affiliation:

1. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

2. Center for Depression Research and Clinical Care, Peter O’Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

3. Jane and John Justin Neurosciences Center, Cook Children’s Health Care System, Fort Worth, TX 76104, USA

4. Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA

5. McLean Hospital, Belmont, MA 02478, USA

6. Department of Psychology, University of Texas at Arlington, Arlington, TX 76019, USA

7. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA

8. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA

9. Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA

10. Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

11. Department of Psychiatry, Columbia University, New York, NY 10032, USA

12. Department of Psychiatry and Behavioral Health, Stony Brook University Renaissance School of Medicine, Stony Brook, NY 11794, USA

13. Massachusetts General Hospital, Boston, MA 02114, USA

Abstract

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged. Data were gathered as part of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a double-blind, placebo-controlled clinical trial of antidepressant response. Participants included 195 individuals with moderate to severe MDD (Quick Inventory of Depressive Symptomatology (QIDS–SR) score ≥ 15), not in treatment for depression, and with complete PRT data. Healthy controls (n = 40) had no history of psychiatric illness, a QIDS–SR score < 8, and complete PRT data. Participants with MDD were treated with sertraline or placebo for 8 weeks (stage I of the EMBARC trial). RBD was applied to PRT data using discriminant analysis, and classified MDD participants as reward task engaged (n = 137) or reward task disengaged (n = 58), relative to controls. Reward task engaged/disengaged groups were compared on sociodemographic features, reward–behavior, and sertraline/placebo response (Hamilton Depression Rating Scale scores). Reward task disengaged MDD participants responded only to sertraline, whereas those who were reward task engaged responded to sertraline and placebo (F(1293) = 4.33, p = 0.038). Reward task engaged/disengaged groups did not differ otherwise. RBD was predictive of reward impairment in depressed patients and may have clinical utility in identifying patients who will benefit from antidepressants.

Funder

National Institute of Mental Health of the National Institutes of Health

Translational Research Activities in Neuropsychiatry

Publisher

MDPI AG

Subject

Behavioral Neuroscience,General Psychology,Genetics,Development,Ecology, Evolution, Behavior and Systematics

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