Asset Type: Publications, In-house Clinical and Imaging Centers, Preclinical Imaging, Neuroscience

Effects of antipsychotics on human cognitive function: causal evidence from healthy volunteers following sustained D2/D3 antagonism, D2/D3 partial agonism and placebo

Effects of antipsychotics on human cognitive function: causal evidence from healthy volunteers following sustained D2/D3 antagonism, D2/D3 partial agonism and placebo

How Sustained D2/D3 Modulation Impacts Working Memory Performance

This study provides the first causal evidence in healthy adults that sustained use of both a D2/D3 antagonist (amisulpride) and a D2/D3 partial agonist (aripiprazole) impairs visuospatial working memory (VS-WM). Across a double-blind, placebo-controlled, crossover design, participants experienced slower response times in memory tasks without loss of accuracy, indicating altered speed-accuracy trade-offs. These cognitive effects occurred without broader impacts on sustained attention, response inhibition, or subjective alertness, suggesting a specific effect of dopamine modulation on working memory processes.

Why Read this Publication:

  • First causal evidence of how sustained D2/D3 receptor modulation affects human working memory
  • Clinical relevance with dosing levels commonly prescribed for schizophrenia and other conditions
  • Demonstrates targeted effects on working memory latency without general cognitive decline
  • Highlights dopamine’s role in regulating decision thresholds and working memory retrieval
  • Supports deeper exploration into optimizing antipsychotic therapy while minimizing cognitive burden

Journal: Molecular Psychiatry
Authors: Martin Osugo, Uzma Zahid, Pierluigi Selvaggi, Alexandria Chilimidos, Valeria Finelli, George E. Chapman, Thomas Whitehurst, Ellis Chika Onwordi, Robin M. Murray, Matthew B. Wall, Tiago Reis Marques, Mitul A. Mehta & Oliver D. Howes