Abstract
Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied. A total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression. MMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(β) = 2.100, 95% confidence interval (CI) 1.104-3.993, p = 0.024] and nonremission in CHR individuals [Exp(β) = 1.898, 95% CI 1.065-3.374, p = 0.030]. These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.
Highlights
Stages of psychotic disorder have been regarded as critical periods for early intervention to improve the clinical outcome of the disorder (Correll et al, 2018; Fusar-Poli, McGorry, & Kane, 2017; Lieberman et al, 2001)
Diagnosis based on the symptomatic phenotype produces significant prognostic heterogeneity that interferes with the goal of early intervention in early psychosis; investigation of biomarkers that are predictive of prognostic trajectories of early psychosis patients is warranted (Allswede et al, 2020; Birchwood et al, 1998; Clementz et al, 2016)
In line with many previous studies (Erickson et al, 2016; Higgins et al, 2021; Tateno et al, 2021), deviant MMN (dMMN) amplitudes at the FCz electrode site were impaired in both first-episode psychosis (FEP) and clinical high risk (CHR) patients; these amplitudes were used for further analysis for prognosis prediction
Summary
Stages of psychotic disorder have been regarded as critical periods for early intervention to improve the clinical outcome of the disorder (Correll et al, 2018; Fusar-Poli, McGorry, & Kane, 2017; Lieberman et al, 2001). The concept of clinical high risk (CHR) for psychosis was established for early detection of FEP to shorten the DUP and for delaying or preventing the onset of psychotic disorder (Miller et al, 2002; Yung et al, 2005). Those patients in the early stages of psychotic disorder were proven to be heterogeneous in their prognostic trajectories. These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention
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