Dopaminergic Modulation of Probabilistic Reasoning and Overconfidence in Errors: A Double-Blind Study

Introduction: Reasoning biases such as jumping to conclusions (JTC) and overconfidence in errors have been well replicated in patients with delusions. However, their relation to dopaminergic activity, central to pathophysiologic models of psychosis, has not yet been investigated. This study aimed to examine the effects of a dopaminergic agonist (l-dopa) and a dopaminergic antagonist (haloperidol) on the JTC bias and overconfidence in errors after single-dose administration in healthy individuals. Methods: The study used a randomized, double-blind, placebo-controlled, 3-way crossover design. Participants were 36 healthy individuals aged 18-36 years. The variables of interest were draws to decision and probability threshold to decision on a computerized variant of the beads task and the number of high-confident incorrect responses on a visual memory task. Results: There were no significant effects of substance on draws to decision and probability threshold to decision. A significant effect emerged for high-confident incorrect responses in the memory task; pairwise comparisons indicated a significant reduction of the number of high-confident incorrect responses after administration of haloperidol vs l-dopa and placebo. Conclusions: This is the first study to investigate the direct effects of dopaminergic drugs on reasoning biases. The JTC bias and overconfidence in errors showed a differential pattern of dopaminergic modulation, suggesting that they represent different facets of reasoning abnormalities that interact with each other to produce delusions in susceptible individuals.