P300 and symptom improvement in schizophrenia

Rationale: A reduced amplitude of the auditory evoked P300 was interpreted as a trait marker of schizophrenia but reports about correlations between s chizophrenic psychopathology and P300 amplitude indicate also a state chara cter. Objectives: To shed light upon these trait and state aspects a longit udinal study was per-formed to investigate the influence of symptom improve ment and atypical neuroleptics on the amplitudes of the P300 and their subc omponents. Methods: P300 was recorded in 17 schizophrenic patients before a nd after 4 weeks under either clozapine or olanzapine in a double-blind con trolled design. For comparison, 17 age- and sex-matched healthy subjects we re investigated. Parietal and frontal P300 subcomponents were investigated separately using dipole source analysis. Results: Schizophrenic patients ha d smaller parietal (temporo-basal dipole) but not frontal subcomponent ampl itudes (temporo-superior dipole) than controls. For the whole sample subcom ponent amplitudes did not change over 4 weeks despite clinical improvement but patients with a pronounced improvement of the PANSS positive score show ed a slight enhancement of both subcomponents. This was not significant whe n the P300 amplitude was measured at a single electrode (Pz). No significan t difference between clozapine and olanzapine concerning effects on P300 am plitudes were observed. Conclusions: The results indicate that P300 subcomp onents are modulated by changes of positive but not by changes of negative symptoms or different neuroleptics. This result was obvious for P300 subcom ponents but not for Pz electrode measurement, which may be due to a higher reliability of the dipole source activity. The results can be integrated in to a hypothetical model containing two pathophysiological subgroups of schi zophrenia.