Severity of thought disorder predicts psychosis in persons at clinical high-risk

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Abstract

Background

Improving predictive accuracy is of paramount importance for early detection and prevention of psychosis. We sought a symptom severity classifier that would improve psychosis risk prediction.

Methods

Subjects were from two cohorts of the North American Prodrome Longitudinal Study. All subjects met Criteria of Psychosis-Risk States. In Cohort-1 (n = 296) we developed a classifier that included those items of the Scale of Psychosis-Risk Symptoms that best distinguished subjects who converted to psychosis from nonconverters, with performance initially validated by randomization tests in Cohort-1. Cohort-2 (n = 592) served as an independent test set.

Results

We derived 2-Item and 4-Item subscales. Both included unusual thought content and suspiciousness; the latter added reduced ideational richness and difficulties with focus/concentration. The Concordance Index (C-Index), a measure of discrimination, was similar for each subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI = [0.64, 0.77], Cohort-1: 0.74, 95% CI = [0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI = [0.3, 0.76], Cohort-1: 0.72, 95% CI = [0.66–0.79]). The 4-Item performed better than the 2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects (p-value = 1.3E  55). Subscale calibration between cohorts was proportional (higher scores/lower survival), but absolute conversion risk predicted from Cohort-1 was higher than that observed in Cohort-2, reflecting the cohorts' differences in 2-year conversion rates (Cohort-2: 0.16, 95% CI = [0.13, 0.19]; Cohort-1: 0.30, 95% CI = [0.24, 0.36]).

Conclusion

Severity of unusual thought content, suspiciousness, reduced ideational richness, and difficulty with focus/concentration informed psychosis risk prediction. Scales based on these symptoms may have utility in research and, assuming further validation, eventual clinical applications.

Introduction

Development of preventative interventions for schizophrenia requires identifying persons at very high risk. An early study examining psychosis conversion in persons meeting high-risk diagnostic criteria reported a 45% 2-year conversion rate (Yung et al., 2004), however subsequent studies found 2-year conversion rates that ranged from 15 to 30% (Demjaha et al., 2012, DeVylder et al., 2014, Katsura et al., 2014, Lee et al., 2014, Liu et al., 2011, Nelson et al., 2013, Riecher-Rossler et al., 2009, Ruhrmann et al., 2010, Woods et al., 2009, Ziermans et al., 2011). Efforts are needed to improve psychosis risk prediction.

Prominent among the scales used to evaluate symptoms associated with psychosis risk is the Scale of Psychosis-Risk Symptoms (SOPS) (McGlashan et al., 2010, Miller et al., 2002). The SOPS comprises 19 symptoms in four domains that include: positive (unusual thought content/delusional ideas, suspiciousness/persecutory ideas, grandiose ideas, perceptual abnormalities/hallucinations, disorganized communication), negative (social anhedonia, avolition, decreased expression of emotion, decreased experience of emotions and self, reduced ideational richness, reduced occupational functioning), disorganized (odd behavior or appearance, bizarre thinking, trouble with focus and attention, impaired hygiene), and general (sleep disturbance, dysphoric mood, motor disturbances, impaired stress tolerance). The symptoms evaluated by the SOPS were chosen to reflect broadly the symptoms experienced by persons with schizophrenia during their prodrome.

We sought to identify among items measured by the SOPS subsets that best predicted psychosis conversion. We considered two large independent cohorts, the North American Prodrome Longitudinal Study Cohort-1 and the North American Prodrome Longitudinal Study Cohort-2. This allowed construction of risk prediction subscales in Cohort-1 and evaluation of subscale performance in Cohort-2.

Section snippets

Subjects

Detailed study methods were reported previously (Addington et al., 2007, Addington et al., 2012, Cannon et al., 2008). In brief, the North American Prodrome Longitudinal Study is a multisite observational study of the predictors and mechanisms of conversion to psychosis in persons meeting Criteria of Psychosis-Risk Syndromes (COPS) (Miller et al., 2003). There were two non-overlapping waves of recruitment, Cohort-1 and Cohort-2. For Cohort-1 a database combined the results post hoc from eight

Study subjects (Table 1)

Baseline evaluations for Cohort-1 occurred in 1998–2005 and for Cohort-2 in 2008–2013. Compared to included subjects, excluded subjects had significantly lower parental education in both cohorts. For Cohort-1, the diagnosis at conversion was known for 59 (66%): Bipolar Disorder (n = 6), Brief Psychotic Disorder (n = 2), Delusional Disorder (n = 2), Psychosis NOS (n = 16), Schizoaffective Disorder (n = 6), Schizophrenia (n = 15), and Schizophreniform Disorder (n = 12). For Cohort-2, the diagnosis at

Discussion

The performance of the 2-Item subscale indicates that the severity of unusual thought content (P1), referential thinking (both P1,P2) and suspiciousness (P2) are key high-risk symptoms. The majority of published studies examining symptoms and risk prediction likewise have reported that items reflecting disordered thought content (unusual ideas (Katsura et al., 2014, Nelson et al., 2013, Salokangas et al., 2013, Thompson et al., 2013, Thompson et al., 2011, Wilcox et al., 2014), suspiciousness (

Role of the funding source

This project was a cooperative agreement between the investigator sites and the National Institutes of Health.

Contributors

Drs. Perkins and Jeffries contributed equally to the work. Drs. Perkins and Jeffries undertook the statistical analysis, and Dr. Perkins wrote the first draft of the manuscript. All of the authors were involved in study design, contributed to and have approved the final manuscript.

Conflict of interest

The authors declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence, or be perceived to influence, their work.

Acknowledgments

U01 MH081902 (Cannon), P50 MH066286 (Bearden), U01 MH081857 (Cornblatt), U01 MH82022 (Woods), U01 MH066134 (Addington), U01 MH081944 (Cadenhead), R01, U01 MH066069 (Perkins, Jeffries), MH076989 (Mathalon), U01 MH081928 (Seidman), and U01 MH081988 (Walker).

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