Electrophysiological basis for the ability of olanzapine to improve verbal memory and functional outcome in patients with schizophrenia: a LORETA analysis of P300.

Abnormality of P300 waveforms of event-related potentials (ERPs) has been suggested to represent an aspect of the pathophysiology of schizophrenia. Previous work points to the contribution of altered neural function in discrete brain regions in the left hemisphere to psychotic symptoms and cognitive deficits of schizophrenia. In this study, we sought to determine: 1) if patients with schizophrenia elicit a decreased P300 current source density in brain areas, such as the superior temporal gyrus (STG); 2) if decreased P300 generator density in the left STG is recovered by treatment with the most widely-used antipsychotic drug olanzapine; and 3) if the recovery of P300 source density is associated with improvements of cognitive and functional status. P300 in response to an auditory oddball task, as well as verbal learning memory, psychopathology, and quality of life were evaluated in 16 right-handed patients with schizophrenia before and after treatment with olanzapine for 6 months. ERP data were also obtained from 16 right-handed age and gender-matched normal volunteers. Low resolution electromagnetic tomography (LORETA) analysis was used to obtain current density images of P300. Patients with schizophrenia showed significantly smaller LORETA values in several brain regions in the left side, particularly STG, middle frontal gyrus, and precentral gyrus, compared with control subjects. Six-month treatment with olanzapine significantly increased P300 source density only in the left STG. Positive symptoms, negative symptoms, verbal learning memory, and quality of life were also improved during treatment. Significant correlations were found between the increase in LORETA values of left STG vs. improvements of negative symptoms, as measured by Scale for the Assessment of the Negative Symptoms, and verbal learning memory, as measured by the Japanese Verbal Learning Test. Improvement of quality of life, as evaluated by the Quality of Life Scale, were significantly associated with an increase in LORETA values of middle frontal gyrus, and tended to correlate with that of precentral gyrus. The results of this study suggest that changes in cortical activity, as measured by ERPs, are responsible for the ability of some antipsychotic drugs to improve cognition and functional outcome in patients with schizophrenia.