Auditory P300 as a predictor of short-term prognosis in subjects at clinical high risk for psychosis

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Abstract

Background

The aim of this study was to investigate whether P300 could predict the short-term prognosis of subjects at clinical high risk (CHR) for psychosis who do not convert to psychotic disorder (non-converters).

Method

CHR subjects were examined with auditory P300 at baseline, and their clinical state was regularly assessed up to 2 years. 45 CHR non-converters were divided into remitter and non-remitter groups. Repeated-measures analysis of variance (ANOVA) was performed to compare baseline P300 between the two groups. Multiple regression analysis was used to identify factors predicting symptomatic or functional improvement in CHR subjects during the follow-up period.

Results

There were no group differences in P300 amplitude or latency between CHR remitters and non-remitters. In the multiple regression analysis, P300 amplitude at Pz (β = 0.206, 95% confidence interval [95CI] = 0.035 to 0.567, p = 0.028) significantly predicted later amelioration of the Scale of Prodromal Symptoms (SOPS) negative symptoms. Improvement in SOPS general symptoms was significantly predicted by P300 amplitude at Pz (β = 0.255, 95CI = 0.065 to 0.455, p = 0.010) and mood stabilizer use (β = 0.199, 95CI = 0.081 to 4.154, p = 0.042).

Conclusions

These results indicate that P300 may be a possible predictor of improvement in negative and general symptoms in CHR non-converters. Our findings support the recommendation that a broader concept of assessment guidelines is needed to forecast clinical outcome and provide appropriate interventions for CHR non-converters.

Introduction

Early psychosis detection and intervention have been matters of grave concern for many years. ‘Clinical high risk (CHR)’ or ‘ultra-high risk’ criteria were established to identify subjects at imminent risk of psychotic disorder (Miller et al., 2003, Yung et al., 2004). Although longitudinal studies demonstrated the predictive value of these criteria, the initially reported high transition rates have been decreasing in subjects at CHR for psychosis (Miller et al., 2002, Yung et al., 2007, Simon et al., 2011). Recently, an increasing portion of CHR subjects who do not convert to psychosis (i.e., non-converters) has resulted in more attention being paid to the prognosis of this group (Ziermans et al., 2011, Schlosser et al., 2012).

CHR non-converters are a heterogeneous group in terms of their prognosis, and consist of individuals who are in remission, who are neither remitted nor converted, and who later will convert to psychosis (Velthorst et al., 2011, de Wit et al., 2014). Therefore, early detection of putative remitters in CHR non-converters may be helpful in reducing problems with false positives, such as application of inappropriate treatment and social stigmatization. Furthermore, considering that some CHR non-converters are non-remitters with sustained prodromal symptoms and even symptomatic remitters are remained at poor functional status (Addington et al., 2011, Lee et al., 2014a), factors predictive of the clinical course in CHR non-converters would provide useful guidelines for decision making regarding appropriate interventions. Despite its clinical importance, few studies of prediction of the prognosis of CHR non-converters have been conducted (Lee et al., 2014b, Lin et al., 2015).

In addition, there are studies suggesting that clinical manifestations other than positive prodromal symptoms may be important in subjects at CHR for psychosis (Lencz et al., 2004, Addington et al., 2011, Fusar-Poli et al., 2014). Fusar-Poli et al. reported that Axis I comorbidity of depressive and anxiety disorders is high in CHR subjects, and is associated with negative symptoms and functional impairment (Fusar-Poli et al., 2014). According to Lencz et al., negative symptoms were related with later conversion to psychotic disorder in CHR subjects (Lencz et al., 2004). Addington et al. also noted that attenuated positive symptoms may predict a more severe condition in some cases, but not in all CHR subjects, and thus better predictors are needed (Addington et al., 2011). Therefore, future studies aimed at identifying factors associated with the clinical prognosis of CHR subjects—other than positive prodromal symptoms such as negative symptoms, general symptoms or neurophysiological variables—would be of great interest.

P300 is a late cognitive component of event-related potentials (ERPs), which is thought to reflect a working memory update of change and attention (Nieman et al., 2002). A large number of studies found that P300 amplitude is reduced in patients with schizophrenia, as well as in their biological relatives (Winterer et al., 2003, Bramon et al., 2004). These findings suggest that P300 may be a potential trait marker for psychosis. On the other hand, evidence supporting the notion that P300 could be used as a state marker for symptom severity also exists (Mathalon et al., 2000, Higashima et al., 2003). Therefore, P300 can be simultaneously a trait marker for psychosis and a state marker for symptom change. Thus, P300 can be also useful in predicting the prognosis, in terms of both psychotic transition and symptom change, of subjects at CHR for psychosis.

In CHR subjects, P300 amplitude was found to be reduced compared with that of healthy controls (van der Stelt et al., 2005, Bramon et al., 2008, Ozgurdal et al., 2008). P300 impairment was more severe in CHR converters than that in CHR non-converters, and reduced parietal P300 predicted later development of a psychotic episode (van Tricht et al., 2010, Nieman et al., 2013). However, little is known regarding P300 as a prognosis predictor in subjects at CHR, other than psychotic transition. Regarding recent concern about CHR non-converters and the potential role of P300 as a marker for symptom change, it would be interesting to attempt to predict symptomatic improvement in CHR non-converters using P300.

In this study, we aimed to investigate whether P300 predicts the outcome specifically for CHR subjects who did not convert to psychosis during the 2-year follow-up period. We hypothesized that individuals who remitted from their initial prodromal state would display greater baseline P300 amplitude than those who did not remit. We also hypothesized that greater baseline P300 amplitude would predict more symptomatic and functional improvement in CHR non-converters within 2 years.

Section snippets

Participants

141 CHR subjects were recruited from November 2004 to January 2014 via a prospective, longitudinal CHR study in the Seoul Youth Clinic (Kim et al., 2012). CHR status was assessed using the Structural Interview of Prodromal Symptoms (SIPS) criteria (Miller et al., 2002, Jung et al., 2010). Past and current psychiatric disorders were determined using the Structural Clinical Interview for DSM-IV Axis I (SCID-I). Exclusion criteria included a lifetime diagnosis of psychotic illness, history of

Subject characteristics

At the point of baseline P300 and clinical assessment, all CHR subjects were antipsychotic-naïve; 29 subjects were drug-naïve, 8 subjects were taking antidepressants, 1 subject was taking a mood stabilizer, and 10 subjects were taking benzodiazepines. Among the 45 CHR non-converters who had baseline ERP data and at least one follow-up assessment over 2 years, 19 subjects remitted from CHR status and 26 subjects remained in the prodromal status for psychosis. There was no difference in

Discussion

To our knowledge, this is the first study to investigate short-term prognosis in CHR non-converters using P300. Inconsistent with our initial hypothesis, there was no difference in baseline P300 amplitude between the CHR-R and CHR-NR groups, which were classified according to remission criteria based on improvement in positive prodromal symptoms and general functional status. Nevertheless, P300 peak amplitude significantly predicted later improvement in negative and general symptoms during the

Role of funding source

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (Grant no. 2013R1A2A1A03071089).

Contributors

Minah Kim, Tae Young Lee, Sung Nyun Kim and Jun Soo Kwon designed the study. Minah Kim, Tae Young Lee, and Sung Nyun Kim contributed to the participants' enrollment and clinical assessment. Suji Lee collected event-related potentials (ERPs) data. Minah Kim performed the statistical analysis and wrote the manuscript. Tae Young Lee and Sung Nyun Kim supported the statistical analysis and interpretation of the data. Jun Soo Kwon managed and supervised the whole procedure of this study. All authors

Conflict of interest

All authors have no conflict of interest to declare.

Acknowledgments

The authors have no acknowledgements to make.

References (42)

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