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

Abstract

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.

Dopamine effects on evidence gathering and integration

“…Participants were healthy individuals aged 18-40 years recruited through postings on university recruitment sites. The sample size was calculated based on effect sizes of a previous study by our group 28 on dopaminergic modulation of reasoning biases, with which there was no participant overlap. Exclusion criteria were any past or current psychiatric or neurologic disorder, including substance use disorders; history of schizophrenia or bipolar disorder in a first-degree relative; history of craniocerebral trauma, arterial hypertension, cardiologic or serious medical conditions; pregnancy; or treatment with any psychotropic or other drugs.…”

“…28,32 In 3 successive visits, participants were administered either 100 mg of L-dopa and 25 mg of benserazide, 2 mg of haloperidol, or placebo in randomized order and under double-blind conditions (see Andreou and colleagues 28 for dose selection rationale). The 3 visits were separated by at least 7 days to allow a complete wash-out of the drug with the long er half-time (haloperidol).…”

“…18 Additionally, neurocognitive impairments that are typical for schizophrenia 25 might constitute a confounding factor, as they have been suggested to contribute to reasoning biases. 26,27 For these reasons, a previous study by our group 28 used a complementary approach, investigating the effects of dopaminergic agonists (L-dopa) and antagonists (haloperidol) on delusion-associated reasoning biases in healthy individuals. We observed that, although overconfidence in errors significantly decreased with haloperidol, dopaminergic agents had no effect on evidence gathering.…”

“…We observed that, although overconfidence in errors significantly decreased with haloperidol, dopaminergic agents had no effect on evidence gathering. 28 However, the paradigm used to assess the latter was a variant of the classical beads task, a very simple task consisting of a single trial. 29 Although the validity of this task has been repeatedly confirmed in patients with schizophrenia, 4 it is possible that its simplicity led to insufficient variance and/or practice effects 30,31 that made it difficult to detect effects of single-dose medication in healthy individuals.…”

Neuroenhancement in Healthy Adults, Part I: Pharmaceutical Cognitive Enhancement: A Systematic Review

“…L-DOPA seems to improve encoding but showed no effect on long-term memory and selective attention [65][66][67][68][69][70][71].…”