Effects of a small dose of olanzapine on healthy subjects according to their schizotypy: An ERP study using a semantic categorization and an oddball task

Delusions and hallucinations are often meaningful. They thus reveal abnormal semantic activations. To start testing whether antipsychotics act by reducing abnormal semantic activations we focused on the N400 event-related brain potential, which is elicited by meaningful stimuli, such as words, and whose distribution on the scalp is known to depend on the semantic category of these stimuli. We used a semantic-categorization task specially designed to reduce the impact of the variations of context processing across subjects' groups and a classical oddball task as a control. Healthy subjects were recruited rather than psychotic patients to ensure that the medication effects could not be secondary to a reduction of symptoms. These participants (n=47) were tested in a double-blind cross-over paradigm where the ERP effects of 2.5 mg of olanzapine taken on the eve of the testing were compared to those of the placebo. The amplitudes of the N400s elicited by the target words were greater at anterior scalp sites in the half of the subjects having higher schizotypal scores. Olanzapine reduced these larger N400s and had no effect on the small anterior N400s of the half of the subjects with lower scores. These results are discussed as consistent with the idea that antipsychotics reduce abnormal activations of particular semantic representations. Further studies should thus be done to see if this reduction correlates with and predicts the decrease of psychotic symptoms in patients.