Decreased production of reactive oxygen species by blood monocytes caused by clozapine correlates with EEG slowing in schizophrenic patients

We have earlier reported an increased theta-power value in clozapine (CLO)-treated patients with schizophrenia, nonresponsive to conventional antipsychotics. We also found that the decrease in the production of reactive oxygen species (ROS), induced by CLO, by peripheral blood monocytes (MO) of these patients correlates with clinical improvement. MO share the capability of ROS production with their more mature descendants, microglia of the brain. We hypothesized that the CLO-related changes in peripheral blood MO might be related to a parallel process in microglia and thus be reflected in brain activity. In those 8 patients for whom both QEEG and MO data were available, we explored possible relationships between these parameters. A clear-cut correlation between ROS production (R(2) = 0.929, p < 0.05) for nonstimulated MO, and (R(2) = 0.907, p < 0.001) for stimulated MO and theta-power values in the central frontal electrode (F(z)) was found. It is intriguing to speculate that the EEG slowing is a result of the modulatory action of the activated microglial cells in the central nervous system via production of ROS or cytokines or both. However, this proposition has to be confirmed by future research.