Dopamine D2 receptor antagonism modulates antidepressant placebo effects on reward sensitivity in healthy participants
Description
Content:
Open code and data for the manuscript "Augustat, N., Lee, E., Ahn, W. Y., Chuang, L. C., Endres, D., Mueller, E.: Dopamine D2 receptor antagonism modulates antidepressant placebo effects on reward sensitivity in healthy participants".
Abstract:
"Although antidepressant placebo effects are well-known, their underlying mechanisms are not fully understood yet. Given that (i) depression has been related to aberrant dopamine signaling and (ii) placebo effects in Parkinson’s disease have been linked to dopamine, antidepressant placebo effects may likewise be driven by dopamine. More specifically, positive treatment expectations may lead to changes in dopamine and enhance the sensitivity for reward, which is frequently reduced in depression and anhedonia. The goal of this study was to test whether treatment expectations generally affect dopamine-related reward sensitivity in healthy individuals.
In a double-blind 2x2 design with N=272 participants, we verbally induced antidepressant treatment expectations (high vs. low), crossed with oral intake of a highly selective dopamine D2/3 receptor antagonist (sulpiride 400mg) vs. placebo. Afterwards, participants performed a probabilistic selection task capturing reward sensitivity, presumably related to dopamine functioning. We performed an extensive computational model fitting procedure, including recovery and comparison of 74 different reinforcement learning models using a hierarchical Bayesian sampling method, to enable a reliable parameter estimation.
We found that high treatment expectations increased learning rate in the winning model, which was parametrized by a learning rate, forgetting rate, and inverse temperature. While learning rate was not modulated by sulpiride intake, sulpiride specifically decreased inverse temperature under high treatment expectations. Higher learning rates reflect higher reward sensitivity, while higher inverse temperatures indicate more random choices. Our results thus provide evidence that antidepressant treatment expectations particularly affect reward sensitivity, which is partially modulated by dopamine."
Files
Document
Type
Size
Creative Commons license
Except where otherwised noted, this item's license is described as Attribution 4.0 International