Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Byrne Jonah F, Healy Colm, Föcking Melanie, Susai Subash Raj, Mongan David, Wynne Kieran, Kodosaki Eleftheria, Heurich Meike, de Haan Lieuwe, Hickie Ian B, Smesny Stefan, Thompson Andrew, Markulev Connie, Young Alison Ruth, Schäfer Miriam R, Riecher-Rössler Anita, Mossaheb Nilufar, Berger Gregor, Schlögelhofer Monika, Nordentoft Merete, Chen Eric Y H, Verma Swapna, Nieman Dorien H, Woods Scott W, Cornblatt Barbara A, Stone William S, Mathalon Daniel H, Bearden Carrie E, Cadenhead Kristin S, Addington Jean, Walker Elaine F, Cannon Tyrone D, Cannon Mary, McGorry Pat, Amminger Paul, Cagney Gerard, Nelson Barnaby, Jeffries Clark, Perkins Diana, Cotter David R
Аннотация
Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.