1. Serum immune markers and transition to psychosis in individuals at clinical high risk
- Author
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Valeria Mondelli, Graham Blackman, Matthew J. Kempton, Thomas A. Pollak, Conrad Iyegbe, Lucia R. Valmaggia, Paul Amminger, Neus Barrantes-Vidal, Rodrigo Bressan, Mark van der Gaag, Lieuwe de Haan, Marie-Odile Krebs, Merete Nordentoft, Stephan Ruhrmann, Anita Riecher-Rössler, Bart P.F. Rutten, Gabriele Sachs, Nikolaos Koutsouleris, Philip McGuire, Clinical Psychology, and APH - Mental Health
- Subjects
DISRUPTION ,EXPRESSION ,DISORDER ,SDG 16 - Peace ,Immunology ,Behavioral Neuroscience ,SDG 3 - Good Health and Well-being ,SCHIZOPHRENIA ,Inflammation ,PLASMA ,Endocrine and Autonomic Systems ,Interleukin-6 ,SDG 16 - Peace, Justice and Strong Institutions ,SDG 10 - Reduced Inequalities ,Psychosis ,Clinical high risk ,VEGF ,Justice and Strong Institutions ,1-YEAR FOLLOW-UP ,1ST-EPISODE PATIENTS ,Transition ,ENDOTHELIAL GROWTH-FACTOR ,ONSET ,Cytokines ,Immune markers - Abstract
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.
- Published
- 2023