Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum

• Grant number: 19/13229-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2019
• End date: July 31, 2024
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Cristina Marta Del-Ben
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 21/07448-3 - Immunophenotype of immune-active psychosis patients and the role of interleukin-6, BE.EP.DR

Abstract

According to theories of a psychosis continuum, Psychotic-Like Experiences (PLEs) are present in a significant proportion of the general population, increasing in 5 to 16 times the future risk of transiting toward a schizophrenia-spectrum disorder. Growing body of evidence suggests a role of the immune system in psychosis; hitherto, little is known about alterations of inflammatory markers prior to the onset of psychosis. Aim: To investigate innate and adaptive immune-related markers (monocyte type-1: IL-1², TNF-±, IL-6; T helper 1: IFN-³; monocyte type-2: IL-10; T helper 2: IL-4; and T regulatory: IL-10, TGF-²) as predictors of the positive, negative, depressive and total dimensions of PLEs, as well as associations with the degree of suffering caused by such experiences, in non-psychotic population-based participants and unaffected siblings of first-episode psychosis patients, while adjusting for potential confounders (age, gender, BMI, tobacco smoking, psychoactive substances, years of study). Methods: This study is part of the epidemiological investigation named STREAM (Schizophrenia and other psychoses translational research: environment and molecular biology), conducted in the Ribeirão Preto-SP (Brazil) catchment area. The STREAM study is part of the international multicentre consortium EU-GEI (European Network of National Schizophrenia Networks Studying Gene-Environment Interactions). We will include 257 population-based controls and 75 unaffected siblings of patients with psychosis, aged between 16 and 64 years for both sexes. The three dimensions of PLEs will be evaluated by the Community Assessment of Psychic Experiences, and cytokines will be measured using the multiplex technology. The investigation of inflammatory mediators in phases that precede psychosis can potentially assist in the identification of high-risk subjects and in the prediction of transition to psychosis, facilitating target intervention strategies. Research Abroad (BEPE): In a subsample of participants, we plan to investigate the association between the aforementioned inflammatory markers and the network connectivity through resting-state fMRI. Linking blood-based biomarkers with neuroimage will help in the understanding of possible neuroanatomic and functional implications underlying the inflammatory processes as well as the understanding of the location and participation of inflammation in psychosis. (AU)

Scientific publications

(20)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CONEN, SILKE; GREGORY, CATHERINE J.; HINZ, RAINER; SMALLMAN, RICHARD; CORSI-ZUELLI, FABIANA; DEAKIN, BILL; TALBOT, PETER S.. Neuroinflammation as measured by positron emission tomography in patients with recent onset and established schizophrenia: implications for immune pathogenesis. MOLECULAR PSYCHIATRY, JUN 2020. (19/13229-2)

LOUREIRO, CAMILA MARCELINO; FACHIM, HELENE APARECIDA; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; JOCA, SAMIA; MENEZES, PAULO ROSSI; DALTON, CAROLINE F.; DEL-BEN, CRISTINA MARTA; LOUZADA-JUNIOR, PAULO; REYNOLDS, GAVIN P.. Epigenetic-mediated N-methyl-D-aspartate receptor changes in the brain of isolated reared rats. Epigenomics, v. 12, n. 22, NOV 2020. (13/08216-2, 16/12195-9, 12/05178-0, 13/11167-3, 12/17626-7, 15/02948-7, 19/13229-2, 17/00624-5)

RAGAZZI, TACIANA C. C.; SHUHAMA, ROSANA; SINVAL, JORGE; MAROCO, JOAO; CORSI-ZUELLI, FABIANA; DA ROZA, DAIANE L.; VAN OS, JIM; MENEZES, PAULO R.; DEL-BEN, CRISTINA M.. Validation of the Portuguese version of the Community Assessment of Psychic Experiences and characterization of psychotic experiences in a Brazilian sample. Revista Brasileira de Psiquiatria, v. 42, n. 4, p. 9-pg., 2020-07-01. (19/13229-2, 12/05178-0, 18/07581-2)

CAMILA MARCELINO LOUREIRO; FABIANA CORSI-ZUELLI; HELENE APARECIDA FACHIM; ROSANA SHUHAMA; ADRIELLE MARTINS DE OLIVEIRA; PAULO ROSSI MENEZES; CAROLINE F. DALTON; PAULO LOUZADA-JUNIOR; SINTIA IOLE BELANGERO; FERNANDA COELI-LACCHINI; et al. Lifetime cannabis use and childhood trauma increase risk of psychosis in carriers of CNR1 genetic variants: findings from the STREAM study. Revista Brasileira de Psiquiatria, v. 45, n. 3, p. 226-235, 2023-07-03. (12/05178-0, 19/13229-2, 17/00624-5, 15/02948-7, 20/15752-1, 13/08216-2, 21/07448-3, 13/11167-3)

CONEN, SILKE; GREGORY, CATHERINE J.; HINZ, RAINER; SMALLMAN, RICHARD; CORSI-ZUELLI, FABIANA; DEAKIN, BILL; TALBOT, PETER S.. Neuroinflammation as measured by positron emission tomography in patients with recent onset and established schizophrenia: implications for immune pathogenesis. MOLECULAR PSYCHIATRY, v. 26, n. 9, p. 5398-5406, SEP 2021. (19/13229-2)

SHUHAMA, ROSANA; ROCHA, VICTORIA HELENA STELZER; LOUREIRO, CAMILA MARCELINO; CORSI-ZUELLI, FABIANA; SANTOS, JAIR LICIO FERREIRA; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA. Social and clinical features associated with duration of untreated psychosis in the Brazilian STREAM study. ASIAN JOURNAL OF PSYCHIATRY, v. 65, p. 3-pg., 2021-09-07. (19/13229-2, 13/11167-3, 12/05178-0)

CORSI-ZUELLI, FABIANA; DEAKIN, BILL. Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 125, p. 637-653, JUN 2021. (19/13229-2)

FOLEY, EIMEAR M.; GRIFFITHS, SIAN LOWRI; MURRAY, ALEXANDER; ROGERS, JACK; CORSI-ZUELLI, FABIANA; HICKINBOTHAM, HANNAH; WARWICK, ELLA; WILSON, MARTIN; KASER, MUZAFFER; MURRAY, GRAHAM K.; et al. Protocol for the Psychosis Immune Mechanism Stratified Medicine (PIMS) trial: a randomised double-blind placebo-controlled trial of single-dose tocilizumab in patients with psychosis. BMJ OPEN, v. 13, n. 3, p. 10-pg., 2023-02-01. (19/13229-2, 21/07448-3)

CORSI-ZUELLI, FABIANA; MARQUES, LEONARDO; DA ROZA, DAIANE LEITE; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Cannabis Consumption Increases Risk of Psychosis in a Subgroup of Patients With High Peripheral Blood Inflammation. BIOLOGICAL PSYCHIATRY, v. 87, n. 9, p. 1-pg., 2020-05-01. (13/08216-2, 19/13229-2, 12/05178-0)

CORSI-ZUELLI, FABIANA; CARVALHO RAGAZZI, TACIANA CRISTINA; LOUREIRO, CAMILA MARCELINO; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Signals of Adaptive Immune Activation in Non-Clinical Populations With Psychotic Experiences. BIOLOGICAL PSYCHIATRY, v. 89, n. 9, p. 1-pg., 2021-05-01. (13/08216-2, 19/13229-2, 12/05178-0)

RAGAZZI, TACIANA C. C.; SHUHAMA, ROSANA; SINVAL, JORGE; MAROCO, JOAO; CORSI-ZUELLI, FABIANA; DA ROZA, DAIANE L.; VAN OS, JIM; MENEZES, PAULO R.; DEL-BEN, CRISTINA M.. Validation of the Portuguese version of the Community Assessment of Psychic Experiences and characterization of psychotic experiences in a Brazilian sample. Revista Brasileira de Psiquiatria, v. 42, n. 4, p. 389-397, JUL-AUG 2020. (18/07581-2, 19/13229-2, 12/05178-0)

LOUREIRO, CAMILA MARCELINO; DA ROZA, DAIANE LEITE; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; FACHIM, HELENE APARECIDA; SIMOES-AMBROSIO, LIVIA MARIA CORDEIRO; DEMINICE, RAFAEL; JORDAO, ALCEU AFONSO; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA; et al. Plasma amino acids profile in first-episode psychosis, unaffected siblings and community-based controls. SCIENTIFIC REPORTS, v. 10, n. 1, DEC 8 2020. (13/11167-3, 16/12195-9, 18/07581-2, 17/00624-5, 15/02948-7, 19/13229-2)

CHAUDHRY, I. B.; HUSAIN, M. O.; KHOSO, A. B.; HUSAIN, I, M.; BUCH, M. H.; KIRAN, T.; FU, B.; BASSETT, P.; QURASHI, I; RAHMAN, R. UR; et al. A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis. TRANSLATIONAL PSYCHIATRY, v. 10, n. 1, DEC 30 2020. (19/13229-2)

CORSI-ZUELLI, FABIANA; DEAKIN, BILL; LIMA, MIKHAEL HARUO FERNANDES DE; QURESHI, OMAR; BARNES, NICHOLAS M.; UPTHEGROVE, RACHEL; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 17, p. 14-pg., 2021-11-01. (12/05178-0, 13/08216-2, 20/02642-3, 19/13229-2, 21/07448-3)

FACHIM, HELENE A.; CORSI-ZUELLI, FABIANA; LOUREIRO, CAMILA M.; IAMJAN, SRI-ARUN; SHUHAMA, ROSANA; JOCA, SAMIA; MENEZES, PAULO ROSSI; HEALD, ADRIAN; LOUZADA-JUNIOR, PAULO; DALTON, CAROLINE F.; et al. Early-life stress effects on BDNF DNA methylation in first-episode psychosis and in rats reared in isolation. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 108, JUN 8 2021. (12/05178-0, 12/17626-7, 13/11167-3, 17/00624-5, 13/08216-2, 19/13229-2, 17/17480-6, 15/02948-7)

LOUREIRO, CAMILA M.; FACHIM, HELENE A.; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; MENEZES, PAULO R.; DALTON, CAROLINE F.; DEL-BEN, CRISTINA M.; REYNOLDS, GAVIN P.; LOUZADA-JUNIOR, PAULO. The relationship of childhood trauma and DNA methylation of NMDA receptor genes in first-episode schizophrenia. Epigenomics, v. 13, n. 12, p. 927-937, JUN 2021. (12/05178-0, 13/11167-3, 17/00624-5, 16/12195-9, 19/13229-2, 15/02948-7, 13/08216-2)

CORSI-ZUELLI, FABIANA. One size does not fit all: trans-diagnostic immune signatures for personalized treatment of psychoses. Revista Brasileira de Psiquiatria, v. 44, n. 2, p. 2-pg., 2022-03-01. (19/13229-2, 21/07448-3)

CORSI-ZUELLI, FABIANA; QUATTRONE, DIEGO; CARVALHO RAGAZZI, TACIANA CRISTINA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; VAN OS, JIM; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Low-Grade Inflammation, Familial Liability and the Psychosis Continuum Model. BIOLOGICAL PSYCHIATRY, v. 91, n. 9, p. 2-pg., 2022-05-01. (21/07448-3, 19/13229-2)

CORSI-ZUELLI, FABIANA; MARQUES, LEONARDO; DA ROZA, DAIANE LEITE; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; DI FORTI, MARTA; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. The independent and combined effects of cannabis use and systemic inflammation during the early stages of psychosis: exploring the two-hit hypothesis. PSYCHOLOGICAL MEDICINE, v. N/A, p. 11-pg., 2021-03-19. (12/05178-0, 17/13353-0, 13/11167-3, 13/08216-2, 19/13229-2, 18/07581-2)

CORSI-ZUELLI, FABIANA; HENRIQUES SCHNEIDER, AYDA; SANTOS-SILVA, THAMYRIS; MARCELINO LOUREIRO, CAMILA; SHUHAMA, ROSANA; ROSSI MENEZES, PAULO; SILVEIRA GUIMARAES, FRANCISCO; VILLELA GOMES, FELIPE; QUEIROZ CUNHA, FERNANDO; LOUZADA, PAULO; et al. Increased blood neutrophil extracellular traps (NETs) associated with early life stress: translational findings in recent-onset schizophrenia and rodent model. TRANSLATIONAL PSYCHIATRY, v. 12, n. 1, p. 11-pg., 2022-12-26. (13/08216-2, 13/11167-3, 18/17597-3, 12/05178-0, 19/19190-0, 19/13229-2, 21/07448-3, 20/15752-1, 17/24304-0)