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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
Effective date (Start): September 01, 2019
Effective date (End): 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


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)

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Scientific publications (9)
(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, v. 26, n. 9, p. 5398-5406, . (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, . (13/08216-2, 16/12195-9, 12/05178-0, 13/11167-3, 12/17626-7, 15/02948-7, 19/13229-2, 17/00624-5)
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, . (19/13229-2)
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, . (19/13229-2)
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, . (18/07581-2, 19/13229-2, 12/05178-0)
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, . (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, . (12/05178-0, 13/11167-3, 17/00624-5, 16/12195-9, 19/13229-2, 15/02948-7, 13/08216-2)
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, . (19/13229-2)
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, . (13/11167-3, 16/12195-9, 18/07581-2, 17/00624-5, 15/02948-7, 19/13229-2)

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