P300 subcomponent abnormalities in schizophrenia: I. Physiological evidence for gender and subtype specific differences in regional pathology.

BACKGROUND

P300 event-related brain potential (ERP) amplitude is reduced in patients with schizophrenia. Little attention has been paid to gender differences underlying this abnormality, despite clinical differences between male and female schizophrenics. Studies have also largely ignored the fact that the P300 represents the activity of multiple neural generators and have not assessed the separate activity of different subcomponents.

METHODS

Auditory P300 ERPs were recorded from 65 patients (42 male, 23 female) and 48 controls (30 male, 18 female). Positive and negative symptoms were assessed with standardized rating scales, and patients were subtyped as deficit or nondeficit. Five P300 subcomponents were identified using current source density measures: frontal (P3f), bilateral parietal (P3pL, P3pR), and bilateral temporal (P3tL, P3tR).

RESULTS

Three subcomponents (P3tL, P3f, P3pR) were reduced in patients. The left temporal (P3tL) deficit was common across patient groups, but the overall profile of P300 abnormalities varied by gender and deficit/nondeficit status. Women had greater P3tL and P3f decrements; P3pR was abnormal in men. Deficit and nondeficit patients resembled men and women, respectively, independent of gender. P3f and P3tL amplitudes were correlated and unrelated to symptomatology. P3pR was related to Brief Psychiatric Rating Scale score.

CONCLUSIONS

A left temporal abnormality exists in schizophrenia, along with two different profiles of regional pathology, which segregate by gender and deficit/nondeficit status. This supports the hypothesis of two distinct illness subtypes and suggests a physiological basis for phenotypic gender and deficit/nondeficit differences. P300 subcomponent abnormalities may serve as subtype markers. Correlated left temporal and frontal dysfunction is consistent with a frontotemporal neural network disturbance in some schizophrenics. Further investigation of the longitudinal stability and familial inheritance of these subcomponent abnormalities is warranted.