Abstract

BackgroundSchizophrenia and related disorders have heterogeneous outcomes. Predicting long-term psychosis outcome may be helpful in improving treatment decision making. The aim of our study was to develop and validate a long-term outcome prediction model of psychosis in individual patients. Many studies have shown that outcome is related to symptoms, demographic, clinical, cognitive, genetic and environmental data – at the level of correlations. We hypothesized that, using machine learning (ML), it is possible to predict individual long-term outcome based on patterns that are present in these data at baseline. Second, we test if variables that were recently found to be predictive of short-term outcome (European First Episode Schizophrenia Trial (EUFEST), Koutsouleris et al, 2016) can yield accurate long-term outcome predictions in our sample.MethodsThis study included 523 patients (mean (SD) age = 27.6 (7.4) year) from the Genetic Risk and Outcome of Psychosis study. The study extensively assessed patients at baseline, 3- and 6-year follow-up. Outcome was defined in two ways: 1) Symptomatic: being in remission (good outcome) or not in remission (poor outcome), according to the Remission Tool (i.e. a consensus definition which defines remission as maintaining core DSM symptoms, based on Positive and Negative Symptom Scale [PANSS] on a low level during ≥6 months); and 2) Functional, using Global Assessment of Functioning (GAF) scale, divided into good (GAF≥65) and poor (GAF <65) outcome. A support vector machine was trained to predict outcome based on (combinations of) the following sets of baseline data: PANSS, clinical and demographic variables, substance use, neurocognitive/ social cognitive tasks, premorbid adjustment, need of care items (CANSAS), extrapyramidal symptoms, genetic features, environmental variables; and the sets of predictors from 4- and 52-week GAF-based outcome prediction models from the EUFEST study. We trained full and leaner models, using recursive feature elimination (RFE). We tested performance of outcome prediction models using nested cross-validation, i.e., predicting outcome in patients not part of the training set.Results6-year functional outcome (i.e. GAF status) was best predicted by a multi-modal model based on baseline PANSS, CANSAS, clinical and demographic variables, using RFE: 75% of the patients was correctly predicted. Significant predictions using single-modal models were obtained for baseline PANSS (62.7%), clinical (60.9%) and CANSAS predictors (58.0%). For functional outcome (GAF) at 6 years, also baseline PANSS, clinical and CANSAS related features produced highest accuracies (61.1%, 63.1% and 59.3% resp.). Classification of symptomatic and functional outcome at 3 years yielded comparable results. Replication using the best scoring predictors of 4 and 52 weeks outcome in the EUFEST study resulted in accuracies of 61.5% and 56.5% for remission 3-year outcome; 61.6% and 61.0% for remission 6-year outcome; 60.1% and 57.7% for GAF 3-year outcome; 62.3% and 64.6% for GAF 6-year outcome.DiscussionOur results show that predicting long-term symptomatic and functional outcome can be done with reasonable accuracies of up to 75%. Training a ML algorithm revealed that PANSS, clinical and need of care features predicted our multiple endpoints best. Interestingly, EUFEST predictors included these three types of data as a main part of best performing predictors. We showed that these short-term outcome predictors are, to certain extent (up to 65%), also predictive of long-term outcome. Our study is a promising step in pursuit of personalized medicine applicability in mental care institutes. However, our model needs replication in independent samples.

Highlights

  • Aberrant regulation of dopamine system function is thought to contribute to psychosis in schizophrenia patients; the brain regions associated with this dysregulation have not been conclusively demonstrated

  • Our results using a novel machine learning approach suggest that an ensemble of cognitive, early environmental and genetic features can predict schizophrenia with significant accuracy

  • We have recently demonstrated that medium spiny neurons in the nucleus accumbens (NAc) receive convergent input from the ventral hippocampus and paraventricular nucleus of the thalamus (PVT)

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Summary

Introduction

Aberrant regulation of dopamine system function is thought to contribute to psychosis in schizophrenia patients; the brain regions associated with this dysregulation have not been conclusively demonstrated. These data demonstrate that the vHipp and thalamus ( the PVT) work in concert to regulate VTA dopamine neuron population activity Such data are important as they provide evidence that thalamic abnormalities may contribute to the aberrant dopamine system function observed in schizophrenia and suggest that the PVT may be a novel site for intervention in psychosis. The reverse pattern (i.e., a negative linear relationship and a positive quadratic relationship) was shown in the model for life event distress and memory domain scores (P < 0.01) whilst trauma history showed only a trend-level association with poorer memory performance (P = 0.084) These relationships, which did not differ across CHR and healthy control groups, were largely unchanged after adjusting for demographic factors and salivary cortisol. This study investigated abnormalities in graph-based gyrification connectome in CHR subjects and patients with first-episode psychosis (FEP) and tested the accuracy of this systems-based approach to predict the transition to psychosis among CHR individuals

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