TY - JOUR
T1 - Serum immune markers and transition to psychosis in individuals at clinical high risk
AU - EU-GEI High Risk Study
AU - Mondelli, Valeria
AU - Blackman, Graham
AU - Kempton, Matthew J.
AU - Pollak, Thomas A.
AU - Iyegbe, Conrad
AU - Valmaggia, Lucia R.
AU - Amminger, Paul
AU - Barrantes-Vidal, Neus
AU - Bressan, Rodrigo
AU - van der Gaag, Mark
AU - de Haan, Lieuwe
AU - Krebs, Marie Odile
AU - Nordentoft, Merete
AU - Ruhrmann, Stephan
AU - Riecher-Rössler, Anita
AU - Rutten, Bart P.F.
AU - Sachs, Gabriele
AU - Koutsouleris, Nikolaos
AU - McGuire, Philip
AU - EU GEI High Risk Study
N1 - Funding Information: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. Additional support was provided by a Medical Research Council Fellowship to M Kempton (grant MR/J008915/1). Prof Mondelli, Dr Blackman, Dr Kempton, Prof Valmaggia, and Prof McGuire receive funding support from the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NIHR, or the Department of Health and Social Care. Prof Mondelli is also funded by MQ: Transforming Mental Health (Grant: MQBF/1 and MQBF/4) and the Medical Research Foundation (Grant: MRF-160-0005-ELP-MONDE). Dr Barrantes-Vidal was supported by the Ministerio de Ciencia, Innovación e Universidades (PSI2017-87512-C2-1-R) and the Generalitat de Catalunya (2017SGR1612 and ICREA Academia Award). Funding Information: The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community's Seventh Framework Programme. Additional support was provided by a Medical Research Council Fellowship to M Kempton (grant MR/J008915/1). Prof Mondelli, Dr Blackman, Dr Kempton, Prof Valmaggia, and Prof McGuire receive funding support from the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NIHR, or the Department of Health and Social Care. Prof Mondelli is also funded by MQ: Transforming Mental Health (Grant: MQBF/1 and MQBF/4) and the Medical Research Foundation (Grant: MRF-160-0005-ELP-MONDE). Dr Barrantes-Vidal was supported by the Ministerio de Ciencia, Innovación e Universidades (PSI2017-87512-C2-1-R) and the Generalitat de Catalunya (2017SGR1612 and ICREA Academia Award). Publisher Copyright: © 2023 The Author(s)
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood–brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.
AB - Individuals at clinical high risk (CHR) for psychosis have been found to have altered cytokine levels, but whether these changes are related to clinical outcomes remains unclear. We addressed this issue by measuring serum levels of 20 immune markers in 325 participants (n = 269 CHR, n = 56 healthy controls) using multiplex immunoassays, and then followed up the CHR sample to determine their clinical outcomes. Among 269 CHR individuals, 50 (18.6 %) developed psychosis by two years. Univariate and machine learning techniques were used to compare levels of inflammatory markers in CHR subjects and healthy controls, and in CHR subjects who had (CHR-t), or had not (CHR-nt) transitioned to psychosis. An ANCOVA identified significant group differences (CHR-t, CHR-nt and controls) and post-hoc tests indicated that VEGF levels and the IL-10/IL-6 ratio were significantly higher in CHR-t than CHR-nt, after adjusting for multiple comparisons. Using a penalised logistic regression classifier, CHR participants were distinguished from controls with an area-under the curve (AUC) of 0.82, with IL-6 and IL-4 levels the most important discriminating features. Transition to psychosis was predicted with an AUC of 0.57, with higher VEGF level and IL-10/IL-6 ratio the most important discriminating features. These data suggest that alterations in the levels of peripheral immune markers are associated with the subsequent onset of psychosis. The association with increased VEGF levels could reflect altered blood–brain-barrier (BBB) permeability, while the link with an elevated IL-10/IL-6 ratio points to an imbalance between anti- and pro-inflammatory cytokines.
KW - Clinical high risk
KW - Cytokines
KW - Immune markers
KW - Inflammation
KW - Interleukin-6
KW - Psychosis
KW - Transition
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=85150758749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85150758749&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbi.2023.03.014
DO - https://doi.org/10.1016/j.bbi.2023.03.014
M3 - Article
C2 - 36940754
SN - 0889-1591
VL - 110
SP - 290
EP - 296
JO - Brain, behavior, and immunity
JF - Brain, behavior, and immunity
ER -