Predicting Remission in Subjects at Clinical High Risk for Psychosis Using Mismatch Negativity

Abstract

Background: The declining transition rate to psychotic disorder and the increasing rate of nonpsychotic poor outcomes among subjects at clinical high risk (CHR) for psychosis have increased the need for biomarkers to predict remission regardless of transition. This study investigated whether mismatch negativity (MMN) predicts the prognosis of CHR individuals during a 6-year follow-up period.

Methods: A total of 47 healthy control (HC) subjects and 48 subjects at CHR for psychosis participated in the MMN assessment. The clinical statuses of the CHR subjects were examined at baseline and regularly for up to 6 years. The CHR subjects were divided into remitter and nonremitter groups, and the baseline MMN amplitudes and latencies were compared across the remitter, nonremitter, and HC groups. Regression analyses were performed to identify the predictive factors of remission, the improvement of attenuated positive symptoms, and functional recovery.

Results: CHR nonremitters showed reduced MMN amplitudes at baseline compared to CHR remitters and HC subjects. A logistic regression analysis revealed that the baseline MMN amplitude at the frontal electrode site was the only significant predictor of remission. In a multiple regression analysis, the MMN amplitude, antipsychotic use, and years of education predicted an improvement in attenuated positive symptoms. The MMN amplitude at baseline predicted functional recovery.

Conclusions: These results suggest that MMN is a putative predictor of prognosis regardless of the transition to psychotic disorder in subjects at CHR. Early prognosis prediction and the provision of appropriate interventions based on the initial CHR status might be aided using MMN.

Figures

Fig. 1.

(a) Grand-averaged mismatch negativity (MMN) waveforms across the healthy controls (HC) and subjects at clinical high risk (CHR) for psychosis who remitted (CHR-R) or did not remit (CHR-NR). (b) The MMN amplitudes at the Fz and FCz electrode sites across the groups. The horizontal lines in the group indicate the means, and the vertical lines in the group indicate the10 to 90 percentile. * indicates that the mean difference is significant at the .05 level; ** indicates that the mean difference is significant at the .005 level. (c) Two-dimensional topographic maps of MMN in the HC, CHR-R, CHR-NR, and CHR-T subjects. The 6 frontocentral electrodes are indicated by an x in the topographic maps. The colored bar with numbers indicates the amplitude of MMN (μV).

Fig. 2.

The correlation between the change in the Global Assessment of Functioning (GAF) scores and the MMN amplitude at baseline (left). The partial correlation between the baseline MMN amplitude at Fz and the change in the Scale of Prodromal Symptoms (SOPS) positive symptom scores adjusted for the olanzapine equivalent antipsychotic dose and education years (right). The subjects at CHR who transitioned to psychosis are indicated by the open circles.