Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study.

Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are highly heterogeneous in terms of symptom expression and underlying disease biological mechanisms, thereby impeding the identification of one-size-fits-all predictors of treatment response. We have used a clustering approach to stratify 325 FEP patients into four clinical subtypes, termed C1A, C1B, C2A and C2B, based on their symptoms assessed using the Positive and Negative Syndrome Scale (PANSS) scale. Compared to C1B, C2A and C2B patients, those from the C1A subtype exhibited the most severe symptoms and were the most at risk of being non-remitters when treated with the second-generation antipsychotic drug amisulpride. Before treatment, C1A patients exhibited higher serum levels of several pro-inflammatory cytokines and inflammation-associated biomarkers therefore validating our stratification approach on external biological measures. Most importantly, in the C1A subtype, but not others, lower serum levels of interleukin (IL)-15, higher serum levels of C-X-C motif chemokine 12 (CXCL12), previous exposure to cytomegalovirus (CMV), use of recreational drugs and being younger were all associated with higher odds of being non-remitters 4 weeks after treatment. The predictive value of this model was good (mean area under the curve (AUC) = 0.73 ± 0.10), and its specificity and sensitivity were 45 ± 0.09% and 83 ± 0.03%, respectively. Further validation and replication of these results in clinical trials would pave the way for the development of a blood-based assisted clinical decision support system in psychosis.

Correction: Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study.

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Magnetic resonance imaging and the prediction of outcome in first-episode schizophrenia: a review of current evidence and directions for future research.

UNLABELLED: Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient. METHODS: Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness. RESULTS: The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes. CONCLUSION: Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings.