Effects of Blocking D2/D3 Receptors on Mismatch Negativity and P3a Amplitude of Initially Antipsychotic Naïve, First Episode Schizophrenia Patients

BackgroundReduced Mismatch negativity (MMN) and P3a amplitude have been suggestedto be among the core deficits inschizophrenia since the late seventies. Blockade of dopamine D2 receptors play an important role in the treatment of schizophrenia. In addition, there is some evidence indicating that deficits in MMN and P3a amplitudeare related to increased dopaminergic activity. This is the first study investigating the effect of amisulpride, a potent D2-antagonist, on MMN and P3a amplitude in a large group of antipsychotic-naïve, first-episode schizophrenia.MethodFifty-one antipsychotic-naïve, first-episode schizophrenia patients were tested in a MMN paradigm at baseline and after six weeks of treatment with amisulpride. We further examined 48 age and gender matched controls in this paradigm.ResultsAt baseline the patients showed significantly reduced P3a amplitude compared to healthy controls, but no differences in MMN. Although the treatment with amisulpride significantly improved the patients' psychopathological (PANSS) and functional (GAF) scores, it did not influence their MMN amplitude, while also theirreduced P3a amplitude persisted.ConclusionOur findings show that antipsychotic naïve, first-episode patients with schizophrenia have normal MMN, yet reduced P3a amplitude compared to healthycontrols. In spite of the fact that the six weeks amisulpride treatment improved the patients both clinically and functionally, it had no effect on either MMN or P3a amplitude. This suggests that even though there is a dopaminergic involvement in global functioning and symptomatology in schizophrenia, there is no such involvement in these particular measures of early information processing.