Effects of blocking D2/D3 receptors on mismatch negativity and P3a amplitude of initially antipsychotic naïve, first episode schizophrenia patients

Background: Reduced mismatch negativity and P3a amplitude have been suggested to be among the core deficits in schizophrenia since the late 1970s. Blockade of dopamine D2 receptors play an important role in the treatment of schizophrenia. In addition, there is some evidence indicating that deficits in mismatch negativity and P3a amplitude are related to increased dopaminergic activity. This is the first study investigating the effect of amisulpride, a potent D2-antagonist, on mismatch negativity and P3a amplitude in a large group of antipsychotic-naïve, first-episode schizophrenia patients. Methods: Fifty-one antipsychotic-naïve, first-episode schizophrenia patients were tested in a mismatch negativity paradigm at baseline and after 6 weeks of treatment with amisulpride. We further examined 48 age- and gender-matched controls in this paradigm. Results: At baseline, the patients showed significantly reduced P3a amplitude compared with healthy controls, but no differences in mismatch negativity. Although the treatment with amisulpride significantly improved the patients' psychopathological (PANSS) and functional (GAF) scores, it did not influence their mismatch negativity amplitude, while also their reduced P3a amplitude persisted. Conclusion: Our findings show that antipsychotic naïve, first-episode patients with schizophrenia have normal mismatch negativity yet reduced P3a amplitude compared with healthy controls. In spite of the fact that the 6-week amisulpride treatment improved the patients both clinically and functionally, it had no effect on either mismatch negativity 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.