Electrophysiological and neuropsychological predictors of conversion to schizophrenia in at-risk subjects

Patients with schizophrenia show neurophysiological and psychological disturbances before the onset of the illness. Mismatch negativity (MMN), an event-related potential, has been shown to be associated with cognitive function. Specifically, duration MMN (dMMN) amplitudes have been indicated to predict progression to overt schizophrenia in subjects with at-risk mental state. The aim of this article is to provide a hypothesis that a combined assessment of dMMN and neuropsychological performance would enhance accuracy for predicting conversion to schizophrenia in at-risk subjects. Data from these neurocognitive modalities in subjects with first-episode schizophrenia (FES) are also presented. There is accumulated evidence that converters to schizophrenia among at-risk subjects show significantly smaller dMMN amplitudes than those in healthy control (HC) subjects at the frontal lead before the onset. In fact, the amplitudes in these converters have been reported to be similar to those in FES to begin with. dMMN current source density, by means of low-resolution brain electromagnetic tomography, was significantly lower in FES than HC subjects, especially in some medial temporal regions which are implicated in the pathophysiology of schizophrenia. Importantly, dMMN current density in the frontal lobe was positively correlated with working memory performance in FES subjects. These findings indicate the utility of the combination of electrophysiological/neuropsychological assessments for early intervention into patients with schizophrenia and high-risk people.