Abstract

BackgroundIn the early intervention in psychosis, ultra-high risk (UHR) criteria have been used to identify individuals who are prone to develop psychosis. Although the transition rate to psychosis in individuals at UHR is 10% to 30% within several years, some individuals at UHR present with poor prognoses even without transition occurring. Therefore, it is important to identify biomarkers for predicting the prognosis of individuals at UHR, regardless of transition. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR.Materials and MethodsIndividuals at UHR (n = 24) and healthy controls (HC; n = 18) participated in this study. In an auditory oddball paradigm, both dMMN and fMMN were measured at baseline. Remission and neurocognitive function after > 180 days were examined in the UHR group. Remission from UHR was defined as functional and symptomatic improvement using the Global Assessment of Functioning (GAF) score and Scale of Prodromal Symptoms (SOPS) positive subscales. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia (BACS). We examined differences in MMN amplitude at baseline between those who achieved remission (remitters) and those who did not (non-remitters). Multiple regression analyses were performed to identify predictors for functioning, positive symptoms, and neurocognitive function.ResultsCompared with the HC group, the UHR group had a significantly attenuated dMMN amplitude (p = 0.003). In the UHR group, GAF scores significantly improved during the follow-up period (mean value 47.1 to 55.5, p = 0.004). The dMMN amplitude at baseline was significantly larger in the remitter (n = 6) than in the non-remitter group (n = 18) (p = 0.039). The total SOPS positive subscale scores and fMMN amplitude at baseline could predict BACS attention subscore at the follow-up point (SOPS positive subscales, p = 0.030; fMMN, p = 0.041).ConclusionOur findings indicate that dMMN and fMMN predicted remission and neurocognitive function, respectively, in individuals at UHR, which suggests that there are both promising biomarker candidates for predicting prognosis in individuals at UHR.

Highlights

  • Intervention for individuals with schizophrenia is important, as the duration of untreated psychosis is known to predict the outcomes of schizophrenia [1]

  • Individuals at ultra-high risk for psychosis (UHR) were categorized based on whether they met the criteria for brief intermittent psychotic syndrome (BIPS), attenuated positive symptom syndrome (APS), and genetic risk and deterioration syndrome (GRDS)

  • This study assessed whether baseline dMMN and fMMN amplitudes could predict the prognosis of individuals at UHR, regardless of whether they transitioned to psychosis

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Summary

Introduction

Intervention for individuals with schizophrenia is important, as the duration of untreated psychosis is known to predict the outcomes of schizophrenia [1]. A meta-analysis by Simon et al reported that 73% of individuals at UHR did not transition to psychosis within 2 years of follow-up, and the percentage of non-converters who achieved remission from UHR status was 46% [5]. A longitudinal study examining the natural history of 111 non-converted medication-naive individuals at UHR reported an improvement of baseline social and role functions over the course of 2 years. These functions were still significantly lower compared to those of nonpsychiatric participants [8]. It is important to investigate and identify biomarkers for predicting prognoses and allowing for early intervention for individuals at UHR, regardless of whether they transition to psychosis. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR

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