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Impact of early life stress in the inflammatory profile of first episode of psychosis (FEP) patients and in the animal model of post-weaning social isolation

Grant number: 17/17480-6
Support Opportunities:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): March 01, 2018
Effective date (End): August 31, 2018
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Cristina Marta Del-Ben
Grantee:Fabiana Maria das Graças Corsi Zuelli
Supervisor: Valeria Mondelli
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: King's College London, England  
Associated to the scholarship:16/12195-9 - Impact of early life stress in the inflammatory profile of first episode of psychosis (FEP) patients and in the animal model of post-weaning social isolation, BP.MS


Epidemiological studies strongly suggest an association between childhood maltreatment and psychosis, and that the cessation of traumatic experiences may reduce the incidence of psychosis by 33%. Recent investigations started to suggest inflammatory cytokine dysfunction in psychosis, and that childhood adversity may underlie this relationship. Despite of that, only two clinical studies have been published so far. Methodological improvements are needed to better understand the relationship between childhood adversity, psychosis and inflammation. We recruited a sizeable, epidemiologically based sample of 507 participants, composed by 166 first-episode psychosis patients, 76 siblings and 265 population-based controls. In an animal model of schizophrenia ((n=20/group), we analysed cytokines in the peripheral blood (plasma) and target brain areas (hippocampus and pre-frontal cortex). Our preliminary results points to cytokine deregulation in an animal model of schizophrenia. We herein propose to build up on our preliminary results by investigating cytokines abnormalities in the plasma of a sizeable clinical model, and whether different types of childhood adversities may underlie these inflammatory changes. We will include in the analysis the proposed cytokines (IL-6, TNF, IL-10), as well as four extra cytokines (IL-1², IL-4, INF-³, TGF-²) and the potential of moderating factors in the association between childhood trauma and adulthood inflammation. All the analysis will be done in partnership with experts from King's College London, U.K. We strongly believe that this collaboration will bring benefits to the analysis of our data. To the best of our knowledge, this will be the first study to investigate the influence of different types of childhood maltreatment on the low-grade inflammatory profile of a large population-based sample of patients during the first manifestation of psychosis.

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Scientific publications (5)
(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)
LOUREIRO, CAMILA MARCELINO; CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; SHUHAMA, ROSANA; DE SOUZA CHAGAS, NATALIA MOTA; MENEZES, PAULO ROSSI; DEL-BEN, CRISTINA MARTA; LOUZADA-JUNIOR, PAULO. Plasma prevalence of anti-N-methyl-d-aspartate receptor IgG antibodies in early stages of psychosis. Ciênc. saúde coletiva, v. 26, n. 3, p. 1085-1094, . (17/17480-6, 13/08216-2, 13/11167-3, 17/00624-5, 16/12195-9, 12/05178-0, 15/02948-7)
CORSI-ZUELLI, FABIANA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; FACHIM, HELENE APARECIDA; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; MONDELLI, VALERIA; DEL-BEN, CRISTINA MARTA. Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment. PSYCHOLOGICAL MEDICINE, v. 50, n. 7, p. 1139-1147, . (12/05178-0, 16/12195-9, 13/11167-3, 13/08216-2, 17/17480-6, 15/02948-7)
FACHIM, HELENE A.; LOUREIRO, CAMILA M.; CORSI-ZUELLI, FABIANA; SHUHAMA, ROSANA; LOUZADA, JR., PAULO; MENEZES, PAULO ROSSI; DALTON, CAROLINE F.; DEL-BEN, CRISTINA MARTA; REYNOLDS, GAVIN P.. GRIN2B promoter methylation deficits in early-onset schizophrenia and its association with cognitive function. Epigenomics, v. 11, n. 4, p. 401-410, . (12/05178-0, 12/17626-7, 16/12195-9, 13/11167-3, 13/08216-2, 17/17480-6, 15/02948-7)
CORSI-ZUELLI, FABIANA; FACHIM, HELENE APARECIDA; LOUREIRO, CAMILA MARCELINO; SHUHAMA, ROSANA; BERTOZI, GIULIANO; JOCA, SAMIA REGIANE LOURENGO; MENEZES, PAULO ROSSI; LOUZADA-JUNIOR, PAULO; DEL-BEN, CRISTINA MARTA. Prolonged Periods of Social Isolation From Weaning Reduce the Anti-inflammatory Cytokine IL-10 in Blood and Brain. FRONTIERS IN NEUROSCIENCE, v. 12, . (13/11167-3, 13/08216-2, 17/00624-5, 16/12195-9, 15/02948-7, 17/17480-6, 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)

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