PMID- 36940754 OWN - NLM STAT- MEDLINE DCOM- 20230418 LR - 20240313 IS - 1090-2139 (Electronic) IS - 0889-1591 (Linking) VI - 110 DP - 2023 May TI - Serum immune markers and transition to psychosis in individuals at clinical high risk. PG - 290-296 LID - S0889-1591(23)00071-5 [pii] LID - 10.1016/j.bbi.2023.03.014 [doi] 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. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Mondelli, Valeria AU - Mondelli V AD - King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, London, UK; 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, UK. Electronic address: valeria.mondelli@kcl.ac.uk. FAU - Blackman, Graham AU - Blackman G AD - 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, UK; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK. FAU - Kempton, Matthew J AU - Kempton MJ AD - 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, UK; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK. FAU - Pollak, Thomas A AU - Pollak TA AD - King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK. FAU - Iyegbe, Conrad AU - Iyegbe C AD - King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK. FAU - Valmaggia, Lucia R AU - Valmaggia LR AD - 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, UK; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychology, London, UK. FAU - Amminger, Paul AU - Amminger P AD - Centre for Youth Mental Health, University of Melbourne, 35 Poplar Road (Locked Bag 10), Parkville, Victoria 485 3052, Australia. FAU - Barrantes-Vidal, Neus AU - Barrantes-Vidal N AD - Departament de Psicologia Clinica i de la Salut (Universitat Autonoma de Barcelona), Fundacio Sanitaria Sant Pere Claver (Spain), Spanish Mental Health Research Network (CIBERSAM), Australia. FAU - Bressan, Rodrigo AU - Bressan R AD - LiNC - Lab Interdisciplinar Neurociencias Clinicas, Depto Psiquiatria, Escola Paulista de Medicina, Universidade Federal de Sao Paulo - UNIFESP), Australia. FAU - van der Gaag, Mark AU - van der Gaag M AD - VU University, Department of Clinical Psychology and Amsterdam Public Health Research Institute, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands; Parnassia Psychiatric Institute, Department of Psychosis Research, Zoutkeetsingel 40, 2512 HN The Hague, The Netherlands. FAU - de Haan, Lieuwe AU - de Haan L AD - AMC, Academic Psychiatric Centre, Department Early Psychosis, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands; Arkin Amsterdam, The Netherlands. FAU - Krebs, Marie-Odile AU - Krebs MO AD - University Paris Descartes, Hopital Sainte-Anne, C'JAAD, Service Hospitalo-Universitaire, Inserm U894, Institut de Psychiatrie (CNRS 3557), Paris, France. FAU - Nordentoft, Merete AU - Nordentoft M AD - Mental Health Center Copenhagen and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Center Glostrup, Mental Health Services in the Capital Region of Copenhagen, University of Copenhagen, Germany. FAU - Ruhrmann, Stephan AU - Ruhrmann S AD - Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany. FAU - Riecher-Rossler, Anita AU - Riecher-Rossler A AD - Medical Faculty, University of Basel, Switzerland. FAU - Rutten, Bart P F AU - Rutten BPF AD - Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, P.O. Box 616, 6200 MD 464 Maastricht, The Netherlands; Max-Planck Institute of Psychiatry, Munich, Germany. FAU - Sachs, Gabriele AU - Sachs G AD - Medical University of Vienna, Department of Psychiatry and Psychotherapy, The Netherlands. FAU - Koutsouleris, Nikolaos AU - Koutsouleris N AD - King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK; Medical University of Vienna, Department of Psychiatry and Psychotherapy, The Netherlands; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany. CN - EU GEI High Risk Study FAU - McGuire, Philip AU - McGuire P AD - 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, UK; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, London, UK. LA - eng GR - MR/J008915/1/MRC_/Medical Research Council/United Kingdom GR - MR/W006251/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230320 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Vascular Endothelial Growth Factor A) RN - 130068-27-8 (Interleukin-10) RN - 0 (Interleukin-6) RN - 0 (Biomarkers) RN - 0 (Cytokines) SB - IM MH - Humans MH - *Vascular Endothelial Growth Factor A MH - Interleukin-10 MH - Interleukin-6 MH - *Psychotic Disorders MH - Biomarkers MH - Cytokines OTO - NOTNLM OT - Clinical high risk OT - Cytokines OT - Immune markers OT - Inflammation OT - Interleukin-6 OT - Psychosis OT - Transition OT - VEGF COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VM has received research funding from Johnson & Johnson as part of a research program on depression and inflammation, but this is unrelated to the work presented in this study. The remaining authors report no conflicts of interest. EDAT- 2023/03/21 06:00 MHDA- 2023/04/18 06:41 CRDT- 2023/03/20 20:21 PHST- 2022/07/20 00:00 [received] PHST- 2023/03/10 00:00 [revised] PHST- 2023/03/16 00:00 [accepted] PHST- 2023/04/18 06:41 [medline] PHST- 2023/03/21 06:00 [pubmed] PHST- 2023/03/20 20:21 [entrez] AID - S0889-1591(23)00071-5 [pii] AID - 10.1016/j.bbi.2023.03.014 [doi] PST - ppublish SO - Brain Behav Immun. 2023 May;110:290-296. doi: 10.1016/j.bbi.2023.03.014. Epub 2023 Mar 20.