Reduced reward learning predicts outcome in major depressive disorder

Abstract

Background: Reduced reward learning might contribute to the onset and maintenance of major depressive disorder (MDD). In particular, the inability to utilize rewards to guide behavior is hypothesized to be associated with anhedonia, a core feature and potential trait marker of MDD. Few studies have investigated whether reduced reward learning normalizes with treatment and/or reward learning predicts clinical outcome. Our goal was to test whether MDD is characterized by reduced reward learning, especially in the presence of anhedonic symptoms, and to investigate the relationship between reward learning and MDD diagnosis after 8 weeks of treatment.

Methods: Seventy-nine inpatients and 63 healthy control subjects performed a probabilistic reward task yielding an objective measure of participants' ability to modulate behavior as a function of reward. We compared reward responsiveness between depressed patients and control subjects, as well as high- versus low-anhedonic MDD patients. We also evaluated whether reward-learning deficits predicted persistence of MDD after 8 weeks of treatment.

Results: Relative to control subjects, MDD patients showed reduced reward learning. Moreover, patients with high anhedonia showed diminished reward learning compared with patients with low anhedonia. Reduced reward learning at study entry increased the odds of a persisting diagnosis of MDD after 8 weeks of treatment (odds ratio 7.84).

Conclusions: Our findings indicate that depressed patients, especially those with anhedonic features, are characterized by an impaired ability to modulate behavior as a function of reward. Moreover, reduced reward learning increased the odds for the diagnosis of MDD to persist after 8 weeks of treatment.

Figure 1

Schematic representation of the probabilistic reward task. In each trial, participants identified (via key press) whether a short or long month stimulus had been presented in the mouthless face on the screen. In approximately 40% of the trials, a positive reinforcement (monetary reward) was presented.

Figure 2

Response bias as a function of blocks for (A) control and MDD group at baseline; (B) control and MDD group at follow up (after 8 weeks); (C) control, low anhedonic (low A) and high anhedonia (high A) group at baseline; and (D) Low A and high A group at baseline, as well as at follow up (after 8 weeks). Error bars denote SEM.

Figure 3

Response bias as a function of blocks for patients with (MDD diagnosis) vs. without (No MDD diagnosis) MDD diagnosis at follow up. Error bars denote SEM.