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In Schizophrenia research ; h5-index 61.0

INTRODUCTION : Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

METHODS : We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction.

RESULTS : Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %).

IMPLICATIONS : Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

Smart Sophie E, Agbedjro Deborah, Pardiñas Antonio F, Ajnakina Olesya, Alameda Luis, Andreassen Ole A, Barnes Thomas R E, Berardi Domenico, Camporesi Sara, Cleusix Martine, Conus Philippe, Crespo-Facorro Benedicto, D’Andrea Giuseppe, Demjaha Arsime, Di Forti Marta, Do Kim, Doody Gillian, Eap Chin B, Ferchiou Aziz, Guidi Lorenzo, Homman Lina, Jenni Raoul, Joyce Eileen, Kassoumeri Laura, Lastrina Ornella, Melle Ingrid, Morgan Craig, O’Neill Francis A, Pignon Baptiste, Restellini Romeo, Richard Jean-Romain, Simonsen Carmen, Španiel Filip, Szöke Andrei, Tarricone Ilaria, Tortelli Andrea, Üçok Alp, Vázquez-Bourgon Javier, Murray Robin M, Walters James T R, Stahl Daniel, MacCabe James H


First episode psychosis, Machine learning, Prediction modelling, Prospective longitudinal cohort, Stratification, Treatment resistant schizophrenia