Dopaminergic influences on emotional decision making in euthymic bipolar patients

Abstract

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F=0.63; p=0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group's pattern was similar to that reported in healthy individuals (treatment × time × block interaction, p<0.05). Analyses of choice strategy using the expectancy valence model revealed that after 8 weeks on pramipexole, BPD patients attended more readily to feedback related to gains than to losses, which could explain the impaired learning. There were no significant changes in mood symptoms over the 8 weeks, and no increased propensity toward manic-like behaviors were reported. Our results suggest that the enhancement of dopaminergic activity influences risk-associated decision-making performance in euthymic BPD. The clinical implications remain unknown.

Figure 1

The Iowa Gambling Task (IGT) results by group pre- and post-treatment. Performance across five blocks on the IGT. The x-axis represents the five blocks of the task, with the left panel marking the performance at baseline and the right panel marking the performance at week 8. A gray-scale rectangle depicts the 8-week treatment trial, during which time no testing was conducted. The y-axis shows the NET score variable, which is calculated by subtracting the total number of cards chosen from the disadvantageous decks from the total number of cards chosen from the advantageous decks.

Figure 2

Choice strategy: Attention to Losses vs Gains. The card-by-card selection strategy employed with scores from the Attention Losses/Gains index of the expectancy valence model. The x-axis is labeled for the two time points (baseline and week 8), with the y-axis representing the ratio of attention given to negative feedback information (losses) relative to positive feedback (wins). Higher scores represent more attention to losses than to gains.