Tolcapone-Enhanced Neurocognition in Healthy Adults: Neural Basis and Predictors.

Background: Failure of procognitive drug trials in schizophrenia may reflect the clinical heterogeneity of schizophrenia, underscoring the need to identify biomarkers of treatment sensitivity. We used an experimental medicine design to test the procognitive effects of a putative procognitive agent, tolcapone, using an electroencephalogram-based cognitive control task in healthy subjects.

Methods: Healthy men and women (n=27; ages 18-35 years), homozygous for either the Met/Met or Val/Val rs4680 genotype, received placebo and tolcapone 200 mg orally across 2 test days separated by 1 week in a double-blind, randomized, counterbalanced, within-subject design.

Effects of acute memantine administration on MATRICS Consensus Cognitive Battery performance in psychosis: Testing an experimental medicine strategy.

Rationale: Pro-cognitive agents for chronic psychotic disorders (CPDs) might be detected via experimental medicine models, in which neural targets engaged by the drug predict sensitivity to the drug's pro-cognitive effects.

Objective: This study aims to use an experimental medicine model to test the hypothesis that "target engagement" predicts pro-cognitive effects of the NMDA antagonist, memantine (MEM), in CPDs.

Methods: MATRICS Consensus Cognitive Battery (MCCB) performance was assessed in CPD (n = 41) and healthy subjects (HS; n = 41) in a double-blind, randomized cross-over design of acute (single dose) MEM (placebo vs.

Memantine Effects On Sensorimotor Gating and Mismatch Negativity in Patients with Chronic Psychosis.

Patients with chronic psychotic disorders (CPD) exhibit deficient sensorimotor gating (measured by prepulse inhibition (PPI) of startle) and mismatch negativity (MMN). In healthy subjects (HS), N-methyl-D-aspartate (NMDA) antagonists like memantine and ketamine increase PPI, and under some conditions, memantine enhances MMN; these findings present a challenge to understanding the basis for deficient PPI and MMN in psychotic disorders, as reduced NMDA activity is implicated in the pathogenesis of these disorders. Here we assessed for the first time the effects of memantine on PPI and MMN in CPD subjects.