Universität zu Köln

Mongan, David ORCID: 0000-0001-7931-9636, Focking, Melanie, Healy, Colm ORCID: 0000-0001-7974-1861, Susai, Subash Raj ORCID: 0000-0002-3818-6504, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby ORCID: 0000-0002-6263-2332, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie-Odile ORCID: 0000-0002-4715-9890, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus ORCID: 0000-0002-8671-1238, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele ORCID: 0000-0002-8359-9877, Pantelis, Christos ORCID: 0000-0002-9565-0238, van der Gaag, Mark ORCID: 0000-0002-3525-6415, de Haan, Lieuwe, Valmaggia, Lucia ORCID: 0000-0001-6099-8464, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P. F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R. and McGuire, Philip ORCID: 0000-0003-4381-0532 (2021). Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence. JAMA Psychiatry, 78 (1). S. 77 - 91. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6238

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Abstract

Question Can plasma proteomic biomarkers aid prediction of transition to psychotic disorder in people at clinical high risk (CHR) of psychosis and adolescent psychotic experiences in the general population? Findings In this diagnostic study of 133 individuals at CHR in EU-GEI and 121 individuals from the general population in ALSPAC, models were developed based on baseline proteomic data, with excellent predictive performance for transition to psychotic disorder in individuals at CHR. In a general population sample, models based on proteomic data at age 12 years had fair predictive performance for psychotic experiences at age 18 years. Meaning Predictive models based on proteomic biomarkers may contribute to personalized prognosis and stratification strategies in individuals at risk of psychosis. This diagnostic study investigates whether proteomic biomarkers may aid the prediction of transition to psychotic disorder in the clinical high-risk state and adolescent psychotic experiences in the general population. Importance Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. Main Outcomes and Measures In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. Results The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99; PPV, 76.9%; and NPV, 100%) and test (AUC, 0.92; PPV, 81.8%; and NPV, 96.8%) data. The ALSPAC subsample (121 participants from the general population with plasma samples available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8%; and NPV, 75.8%). Conclusions and Relevance In individuals at risk of psychosis, proteomic biomarkers may contribute to individualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mongan, David UNSPECIFIED orcid.org/0000-0001-7931-9636 UNSPECIFIED Focking, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Healy, Colm UNSPECIFIED orcid.org/0000-0001-7974-1861 UNSPECIFIED Susai, Subash Raj UNSPECIFIED orcid.org/0000-0002-3818-6504 UNSPECIFIED Heurich, Meike UNSPECIFIED UNSPECIFIED UNSPECIFIED Wynne, Kieran UNSPECIFIED UNSPECIFIED UNSPECIFIED Nelson, Barnaby UNSPECIFIED orcid.org/0000-0002-6263-2332 UNSPECIFIED McGorry, Patrick D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Amminger, G. Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Nordentoft, Merete UNSPECIFIED UNSPECIFIED UNSPECIFIED Krebs, Marie-Odile UNSPECIFIED orcid.org/0000-0002-4715-9890 UNSPECIFIED Riecher-Rossler, Anita UNSPECIFIED UNSPECIFIED UNSPECIFIED Bressan, Rodrigo A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Barrantes-Vidal, Neus UNSPECIFIED orcid.org/0000-0002-8671-1238 UNSPECIFIED Borgwardt, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruhrmann, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachs, Gabriele UNSPECIFIED orcid.org/0000-0002-8359-9877 UNSPECIFIED Pantelis, Christos UNSPECIFIED orcid.org/0000-0002-9565-0238 UNSPECIFIED van der Gaag, Mark UNSPECIFIED orcid.org/0000-0002-3525-6415 UNSPECIFIED de Haan, Lieuwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Valmaggia, Lucia UNSPECIFIED orcid.org/0000-0001-6099-8464 UNSPECIFIED Pollak, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kempton, Matthew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rutten, Bart P. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Whelan, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Cannon, Mary UNSPECIFIED UNSPECIFIED UNSPECIFIED Zammit, Stan UNSPECIFIED UNSPECIFIED UNSPECIFIED Cagney, Gerard UNSPECIFIED UNSPECIFIED UNSPECIFIED Cotter, David R. UNSPECIFIED UNSPECIFIED UNSPECIFIED McGuire, Philip UNSPECIFIED orcid.org/0000-0003-4381-0532 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-606104
DOI:	10.1001/jamapsychiatry.2020.2459
Journal or Publication Title:	JAMA Psychiatry
Volume:	78
Number:	1
Page Range:	S. 77 - 91
Date:	2021
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2168-6238
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SCHIZOPHRENIA; PROTEIN; BLOOD; COMPLEMENT; DEPRESSION; BIOMARKERS; ENVIRONMENT; INDIVIDUALS; CHILDHOOD; DISCOVERY Multiple languages Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60610