Navegando por Palavras-chave "first episode psychosis"

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    Biomarcadores periféricos nos transtornos psicóticos: a influência de características clínicas, estágio da doença e tratamento
    (Universidade Federal de São Paulo (UNIFESP), 2015-10-16) Noto, Cristiano de Souza [UNIFESP]; Brietzke, Elisa Macedo Brietzke [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    INTRODUCTION: Schizophrenia is a chronic disease, with considerable impact on live of individuals and their families. Its origin is related to a complex interaction between genetic and environmental factors during brain development. Despite advances in research, there are no biological markers to confirm the diagnosis, indicate the prognosis, or assist in therapeutic decision. Changes in immune system and oxidation processes have been consistently associated with schizophrenia and markers of these processes emerge as promising biomarkers. However, the current literature is still heterogeneous, and the role of factors such as the use of medication or phenotypic variability remain a challenge to be surmounted. This thesis presents seven studies investigating biomarkers related to inflammation and oxidative stress in different aspects of the disorder. AIMS: To investigate psychotic disorders longitudinally, with a multi-phase and multimodal approach, taking into account clinical heterogeneity. Hence, it was explored the immunological profile and oxidative biomarkers, by evaluating different subgroups of the disease (first episode, drug-naïve patients, the presence of depression, before and after treatment, treatment-resistance). It was also evaluated the relationship between inflammation, oxidative and genetic biomarkers. METHODS: Patients were recruited in their first psychotic episode (FEP), drug-naïve, and followed for an average period of 8 weeks under risperidone. It was also evaluated patients in advanced stages, with more than 1 year of disease. Patients were diagnosed by SCID, with psychopathological evaluation by PANSS and CDSS. RESULTS: FEP patients have increased levels of interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-alpha when compared to healthy controls. They also have increased total reactive antioxidant potential (TRAP) and decreased activity of paraoxonase (PON) 1. Those in FEP with depression had higher levels of IL-4 and TNFalfa compared to those without depression, and increased expression of COMT and decrease expression NDEL1. After treatment with risperidone, the three mentioned cytokines, and additionally, IL-4 reduced significantly, and lipid hydroperoxides (LOOH) levels decreased and PON1 activity increased. Next, it was demonstrated that the combination of five biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of schizophrenia with a sensitivity of 70.0% and a specificity of 89 4%. Treatment resistance patients showed distinct inflammatory profile, with an increase in increased levels of sTNF-R1, sTNF-R2, and MCP-1. Finally, increased levels of IL-6 was associated with reduced expression of AKT1 and DROSHA, while an increase of IL-10 was associated with increased expression NDEL1, DISC1 and MBP. IL-6 also significantly increased expression of AKT1, DICER1, DROSHA and COMT induced by risperidone. DISCUSSION: It was shown that a disorder in the immune system and oxidative balance is already present from the onset of schizophrenia, before the use of antipsychotic drugs. Moreover, it was suggested that risperidone has antioxidative and anti-inflammatory effects. Features such as depression and treatment resistance also presented a specific immunological profile. Finally, it was showed that inflammatory cytokines play an important role in the regulation of oxidative processes and gene expression. Using an innovative approach and seeking for convergence between different methodologies, the results generated new perspectives in understanding the pathophysiological mechanisms underpinning the neurobiology of schizophrenia.