| Grant number: | 18/19823-0 |
| Support Opportunities: | Regular Research Grants |
| Start date: | April 01, 2019 |
| End date: | June 30, 2021 |
| Field of knowledge: | Health Sciences - Medicine - Psychiatry |
| Principal Investigator: | Alexandre Andrade Loch |
| Grantee: | Alexandre Andrade Loch |
| Host Institution: | Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated researchers: | Leda Leme Talib ; Wagner Farid Gattaz |
Abstract
Overview: Schizophrenia is a disorder that affects about 1% of the general population. Science has focused its efforts on research into prodromal states, termed "ultra-high risk," in an attempt to find a way to block conversion to psychosis. Our hypothesis is that the interaction between target genes and exposure to childhood trauma constitute risk factors for the onset of psychosis. Such risk factors would influence neuronal growth and brain maturation via neurotrophins. In a state with altered neurotrophic production, a trigger (psychological, environmental, etc.), would produce the first psychotic outbreak.Objectives: 1) to assess levels of neurotrophins in 4 populations: healthy controls, subjects at risk for psychosis, first psychotic outbreak patients, and individuals with chronic schizophrenia. 2) Evaluate if the levels of neurotrophins and pro-neurotrophins correlate with stages of the disease. 3) To evaluate if, in prodromal states, levels of neurotrophins and pro-neurotrophins can be correlated through the evaluation of the interaction of a series of risk genes with environmental trauma in childhood.Methods: Selection of a representative sample of the population of the city of São Paulo, in two stages (Application of Prodrommal questionaire (PQ) and for those with a score> 18, SIPS application) from the SSAPP study in addition to 30 patients already diagnosed with schizophrenia and 20 patients in the first outbreak from other projects and patients from the LIM-27 Psychosocial Outpatient Clinic. 2700 individuals were initially selected by population sampling, and of these, 236 individuals reached score> 18 in the PQ. Of these, 98 were classified as UHR, 2 as already having a diagnosis of psychosis, and 136 controls. Among the individuals who consented to participate in the study we will analyze serological markers (genotyping and neurotrophins), cognitive evaluation, gestational antecedents, stress level evaluation, level of urbanity, socioeconomic level, religiosity and history of childhood trauma of 80 controls, 80 UHR , 20 first unmedicated psychotic outbreak, and 30 individuals with schizophrenia.The sample will be described in its continuous and categorical variables. Genetic, neurotrophic, and childhood trauma related to risk and schizophrenia will be analyzed by simple correlations (chi-square for categorical variables and Pearson's correlation or Student's t-test for continuous ones) compared to controls. Factors that have some correlation with the risk state, diagnosis, or possibly conversion to psychosis may enter into regression models with other variables. Cluster analysis may also be performed to ascertain whether there are different groups of psychoses; that is, whether there are different combinations of genetic and environmental factors that lead to the same pathway to the development of psychotic symptoms. For this, path analysis may also be employed. (AU)
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