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Article / Publication Details

First-Page Preview

Received: October 22, 2022
Accepted: December 12, 2022
Published online: February 16, 2023

Number of Print Pages: 13
Number of Figures: 3
Number of Tables: 3

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS

Abstract

Introduction: Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). Methods: We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. Results: The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, p = 0.010; IL-2, p = 0.023; IL-6, p = 0.012) and HC (IL-6: p = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (p = 0.028), and IL-6 levels tended toward significance (p = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (p = 0.017) and VEGF (p = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (F = 4.502, p = 0.037, effect size (η2) = 0.051), a group effect related to IL-1β (F = 4.590, p = 0.036, η2 = 0.062), and IL-2 (F = 7.521, p = 0.011, η2 = 0.212), but no time × group effect. Discussion: Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

© 2023 S. Karger AG, Basel

References McGorry PD. Early clinical phenotypes, clinical staging, and strategic biomarker research: building blocks for personalized psychiatry. Biol Psychiatry. 2013 Sep 15;74(6):394–5. Yung AR, McGorry PD, McFarlane CA, Jackson HJ, Patton GC, Rakkar A. Monitoring and care of young people at incipient risk of psychosis. Schizophr Bull. 1996;22(2):283–303. Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A, Schultze-Lutter F, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013 Jan;70(1):107–20. Collin G, Seidman LJ, Keshavan MS, Stone WS, Qi Z, Zhang T, et al. Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program. Mol Psychiatry. 2020;25(10):2431–40. Tang Y, Pasternak O, Kubicki M, Rathi Y, Zhang T, Wang J, et al. Altered cellular white matter but not extracellular free water on diffusion MRI in individuals at clinical high risk for psychosis. Am J Psychiatry. 2019 Oct 1;176(10):820–8. Hamilton HK, Boos AK, Mathalon DH. Electroencephalography and event-related potential biomarkers in individuals at clinical high risk for psychosis. Biol Psychiatry. 2020 Aug 15;88(4):294–303. Lieberman JA, Small SA, Girgis RR. Early detection and preventive intervention in schizophrenia: from fantasy to reality. Am J Psychiatry. 2019 Oct 1;176(10):794–810. Fineberg AM, Ellman LM. Inflammatory cytokines and neurological and neurocognitive alterations in the course of schizophrenia. Biol Psychiatry. 2013 May 15;73(10):951–66. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011 Oct 1;70(7):663–71. Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016 Dec;21(12):1696–709. Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry. 2008 Apr 15;63(8):801–8. O'Connor MF, Bower JE, Cho HJ, Creswell JD, Dimitrov S, Hamby ME, et al. To assess, to control, to exclude: effects of biobehavioral factors on circulating inflammatory markers. Brain Behav Immun. 2009 Oct;23(7):887–97. Smith RS. A comprehensive macrophage-T-lymphocyte theory of schizophrenia. Med Hypotheses. 1992 Nov;39(3):248–57. Smith RS, Maes M. The macrophage-T-lymphocyte theory of schizophrenia: additional evidence. Med Hypotheses. 1995 Aug;45(2):135–41. Schwarz MJ, Muller N, Riedel M, Ackenheil M. The Th2-hypothesis of schizophrenia: a strategy to identify a subgroup of schizophrenia caused by immune mechanisms. Med Hypotheses. 2001 Apr;56(4):483–6. Monji A, Kato T, Kanba S. Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257–65. Kamińska T, Wysocka A, Marmurowska-Michalowska H, Dubas-Slemp H, Kandefer-Szerszeń M. Investigation of serum cytokine levels and cytokine production in whole blood cultures of paranoid schizophrenic patients. Arch Immunol Ther Exp. 2001;49(6):439–45. Ebrinc S, Top C, Oncul O, Başoğlu C, Cavuşlu S, Cetin M. Serum interleukin 1 alpha and interleukin 2 levels in patients with schizophrenia. J Int Med Res. 2002 May–Jun;30(3):314–7. Zeni-Graiff M, Rizzo LB, Mansur RB, Maurya PK, Sethi S, Cunha GR, et al. Peripheral immuno-inflammatory abnormalities in ultra-high risk of developing psychosis. Schizophr Res. 2016 Oct;176(2–3):191–5. Stojanovic A, Martorell L, Montalvo I, Ortega L, Monseny R, Vilella E, et al. Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. 2014 Mar;41:23–32. Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry. 2002 May;159(5):863–5. Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003;29(4):703–15. Zheng L, Wang J, Zhang T, Li H, Li C, Jiang K. The Chinese version of the SIPS/SOPS: a pilot study of reliability and validity. Chin Ment Health J. 2012;26(8):571–6. Zhang T, Li H, Woodberry KA, Seidman LJ, Zheng L, Li H, et al. Prodromal psychosis detection in a counseling center population in China: an epidemiological and clinical study. Schizophr Res. 2014 Feb;152(2–3):391–9. Zhang T, Li H, Woodberry KA, Seidman LJ, Chow A, Xiao Z, et al. Interaction of social role functioning and coping in people with recent-onset attenuated psychotic symptoms: a case study of three Chinese women at clinical high risk for psychosis. Neuropsychiatr Dis Treat. 2015;11:1647–54. Zhang TH, Li HJ, Woodberry KA, Xu LH, Tang YY, Guo Q, et al. Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion. Epidemiol Psychiatr Sci. 2017 Jun;26(3):287–98. McGlashan T, Walsh B, Woods S. The psychosis-risk syndrome: handbook for diagnosis and follow-up. New York: Oxford University Press; 2010. Delaney S, Fallon B, Alaedini A, Yolken R, Indart A, Feng T, et al. Inflammatory biomarkers in psychosis and clinical high risk populations. Schizophr Res. 2019 Apr;206:440–3. Karanikas E, Griveas I, Ntouros E, Floros G, Garyfallos G. Evidence for increased immune mobilization in first episode psychosis compared with the prodromal stage in males. Psychiatry Res. 2016 Oct 30;244:333–8. Karanikas E, Manganaris S, Ntouros E, Floros G, Antoniadis D, Garyfallos G. Cytokines, cortisol and IGF-1 in first episode psychosis and ultra high risk males. Evidence for TNF-α, IFN-γ, ΤNF-β, IL-4 deviation. Asian J Psychiatr. 2017 Apr;26:99–103. Zhang T, Tang X, Li H, Woodberry KA, Kline ER, Xu L, et al. Clinical subtypes that predict conversion to psychosis: a canonical correlation analysis study from the ShangHai at Risk for Psychosis program. Aust N Z J Psychiatry. 2019 Sep 5;54:482–95. Fusar-Poli P, Cappucciati M, Borgwardt S, Woods SW, Addington J, Nelson B, et al. Heterogeneity of psychosis risk within individuals at clinical high risk: a meta-analytical stratification. JAMA Psychiatry. 2016 Feb;73(2):113–20. Capuzzi E, Bartoli F, Crocamo C, Clerici M, Carra G. Acute variations of cytokine levels after antipsychotic treatment in drug-naive subjects with a first-episode psychosis: a meta-analysis. Neurosci Biobehav Rev. 2017 Jun;77:122–8. Fraguas D, Diaz-Caneja CM, Rodriguez-Quiroga A, Arango C. Oxidative stress and inflammation in early onset first episode psychosis: a systematic review and meta-analysis. Int J Neuropsychopharmacol. 2017 Jun 1;20(6):435–44. Misiak B, Bartoli F, Carra G, Stańczykiewicz B, Gładka A, Frydecka D, et al. Immune-inflammatory markers and psychosis risk: a systematic review and meta-analysis. Psychoneuroendocrinology. 2021 May;127:105200. Hayes LN, Severance EG, Leek JT, Gressitt KL, Rohleder C, Coughlin JM, et al. Inflammatory molecular signature associated with infectious agents in psychosis. Schizophr Bull. 2014 Sep;40(5):963–72. Zhang T, Zeng J, Wei Y, Ye J, Tang X, Xu L, et al. Changes in inflammatory balance correlates with conversion to psychosis among individuals at clinical high-risk: a prospective cohort study. Psychiatry Res. 2022 Oct 31;318:114938. Zhang T, Wei Y, Zeng J, Ye J, Tang X, Xu L, et al. Interleukin-2/interleukin-6 imbalance correlates with conversion to psychosis from a clinical high-risk state. Psychiatry Clin Neurosci. 2022 Sep 12;77(1):62–3. Cannon TD, Yu C, Addington J, Bearden CE, Cadenhead KS, Cornblatt BA, et al. An individualized risk calculator for research in prodromal psychosis. Am J Psychiatry. 2016 Oct 1;173(10):980–8. Zhang T, Xu L, Li H, Woodberry KA, Kline ER, Jiang J, et al. Calculating individualized risk components using a mobile app-based risk calculator for clinical high risk of psychosis: findings from ShangHai at Risk for Psychosis (SHARP) program. Psychol Med. 2019 Dec 16;51(4):653–60. Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, et al. Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci. 2003 Nov 26;23(34):10841–51. Khoury R, Nasrallah HA. Inflammatory biomarkers in individuals at clinical high risk for psychosis (CHR-P): state or trait? Schizophr Res. 2018 Sep;199:31–8. Cannon TD, Chung Y, He G, Sun D, Jacobson A, van Erp TGM, et al. Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry. 2015 Jan 15;77(2):147–57. Labad J, Stojanovic-Perez A, Montalvo I, Sole M, Cabezas A, Ortega L, et al. Stress biomarkers as predictors of transition to psychosis in at-risk mental states: roles for cortisol, prolactin and albumin. J Psychiatr Res. 2015 Jan;60:163–9. Focking M, Dicker P, Lopez LM, Cannon M, Schafer MR, McGorry PD, et al. Differential expression of the inflammation marker IL12p40 in the at-risk mental state for psychosis: a predictor of transition to psychotic disorder? BMC Psychiatry. 2016 Sep 20;16(1):326. Smesny S, Milleit B, Schaefer MR, Hesse J, Schlogelhofer M, Langbein K, et al. Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis: results of the randomized controlled Vienna omega-3 study. Schizophr Res. 2017 Oct;188:110–7. Penninx BW, Kritchevsky SB, Yaffe K, Newman AB, Simonsick EM, Rubin S, et al. Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition study. Biol Psychiatry. 2003 Sep 1;54(5):566–72. Kim YK, Na KS, Shin KH, Jung HY, Choi SH, Kim JB. Cytokine imbalance in the pathophysiology of major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1044–53. Article / Publication Details

First-Page Preview

Received: October 22, 2022
Accepted: December 12, 2022
Published online: February 16, 2023

Number of Print Pages: 13
Number of Figures: 3
Number of Tables: 3

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

For additional information: https://www.karger.com/NPS