Impaired P3 generation reflects high-level and progressive neurocognitive dysfunction in schizophrenia.

Abstract

In this study, we assessed the integrity of several components of the event-related potential (ERP) associated with different levels of visual and auditory processing in patients with schizophrenia. The objective was to clarify whether high-level attention-dependent cognitive deficits, as indexed by the P3 component, in patients with schizophrenia are related to or originate from potential preceding deficits at lower levels of information processing, as indexed by earlier-occurring ERP components. Also, given that the auditory P3 amplitude has recently been observed to be inversely correlated with illness duration and, hence, may potentially track the operation of a putative neurodegenerative process across the illness course, we recruited patients with schizophrenia varying greatly in illness duration to attempt to replicate this observation. Multichannel ERPs were recorded in 22 patients with schizophrenia at different stages of illness and 22 age-matched healthy control subjects while they performed a visual and auditory oddball task. Patients displayed smaller P3 amplitudes to visual novel and auditory target stimuli than did control subjects, whereas small or no significant between-group differences were observed in sensory-evoked and cognitive-related ERP components preceding P3. Additionally, patients showed a distinct left-smaller-than-right auditory P3 temporal scalp voltage asymmetry. Furthermore, we replicated previous study results of an inverse correlation between the auditory P3 amplitude and illness duration. These results indicate that high-level attention-dependent cognitive deficits central to schizophrenia do not originate from potential preceding impairments at lower levels of sensory, perceptual, or cognitive processing. The data support the view that schizophrenia is characterized by fundamental deficits in integrative cortical functions that specifically impair the ability to analyze and represent stimulus context to guide behavior. Moreover, abnormalities of the auditory P3 amplitude in schizophrenia seem to reflect a basic underlying pathophysiological process that is present at illness onset and progresses across the illness course.