BackgroundA shorter duration of untreated psychosis has been associated with better prognosis in schizophrenia. In this study, we measured the duration mismatch negativity (dMMN), an event-related potential, and cognitive performance in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these neurocognitive measures predict progression to overt schizophrenia in ARMS subjects.Methodology/Principal FindingsSeventeen ARMS subjects, meeting the criteria of the Comprehensive Assessment of At-Risk Mental State, 31 schizophrenia patients (20 first-episode and 11 chronic) and healthy controls (N = 20) participated in the study. dMMN was measured by an auditory odd-ball paradigm at baseline. Neuropsychological performance was evaluated by the Japanese version of the Brief assessment of cognitive function of schizophrenia (BACS-J). The first-episode schizophrenia group showed significantly smaller amplitudes at frontal electrodes than did control subjects whereas chronic patients elicited smaller amplitudes at frontal and central electrodes, consistent with previous reports. During the follow-up period, 4 out of the 17 ARMS subjects transitioned to schizophrenia (converters) while 13 did not (non-converters). Specifically, dMMN amplitudes of non-converters did not differ from those of healthy controls, while converters showed significantly smaller dMMN amplitudes at some electrodes compared to control subjects. Converters performed significantly worse on tests of working memory, verbal fluency, and attention/information processing than did non-converters. There was a significant positive correlation between dMMN amplitudes at the frontal electrodes and verbal fluency, as measured by the BACS, in the AMRS subjects as a whole.Conclusions/SignificanceARMS subjects who later developed schizophrenia elicited smaller dMMN amplitudes to begin with, compared to non-converters. Notably, we have provided the first evidence for the ability of verbal fluency to predict dMMN amplitudes in ARMS subjects. These findings are expected to add to the efforts for early diagnosis and intervention of schizophrenia.

Introduction: We measured duration mismatch negativity (dMMN), P3a, and reorienting negativity (RON) in subjects with at-risk mental state (ARMS), patients with first-episode or chronic schizophrenia, and healthy volunteers. The main interest was to determine if these event-related potentials provide a biomarker associated with progression to overt schizophrenia in ARMS subjects.Methods: Nineteen ARMS subjects meeting the criteria of the Comprehensive Assessment of ARMS, 38 patients with schizophrenia (19 first-episode and 19 chronic), and 19 healthy controls participated in the study. dMMN, P3a, and RON were measured with an auditory odd-ball paradigm at baseline.Results: During the follow-up period (2.2 years), 4 out of the 19 ARMS subjects transitioned to schizophrenia (Converters) while 15 did not (non-Converters). dMMN amplitudes of Converters were significantly smaller than those of non-Converters at frontal and central electrodes before onset of illness. dMMN amplitudes of non-Converters did not differ from those of healthy controls, while Converters showed significantly smaller dMMN amplitudes compared to control subjects. RON amplitudes were also reduced at frontal and central electrodes in subjects with schizophrenia, but not ARMS. Converter subjects tended to show smaller RON amplitudes compared to non-Converters.Conclusions: Our data confirm that diminished dMMN amplitudes provide a biomarker, which is present before and after the development of psychosis. In this respect, RON amplitudes may also be useful, as suggested for the first time based on longitudinal observations.

IntroductionPatients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia.MethodsData were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J).ResultsPatients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients.ConclusionsThis is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia.

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.

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