INCT 2014: National Institute of Biomarkers in Neuropsychiatry

Abstract

The search for the biological substrate of neuropsychiatric disorders is a pre-requisite for the development of more efficacious therapies and mainly of preventive strategies by means of early diagnosis. The experimental attempts to identify specific markers for the different diseases remain unsuccessful to date. At least partially, these negative results derive from a probable lack of specificity of global alterations of the brain biology for certain clinical conditions. Such lack of specificity may be related to the fact that a common genetic basis may be linked to common abnormalities of the brain structure and function in diseases such as Schizophrenia, Bipolar Disorder and Alzheimers disease. By creating the Instituto Nacional de Ciência e Tecnologia de Biomarcadores em Doenças Neuropsiquiátricas (INBioN National lnstitute for Biomarkers in Neuropsychiatry), we aim to carry out an integrative project bringing together scientists from Brazil and abroad, from different areas of expertise, to search for a greater understanding of such bases of the neuropsychiatric disorders. We will adopt experimental strategies that consider both the biological differences and the similarities among the diagnoses of those three disorders, taking as starting point the rationale that a genetic basis confers a common vulnerability to disorders of brain maturation, plasticity, and function, and that the interactions between such genetic basis and non-genetic factors determines the pathoplasty and the differences in the clinical manifestations. A nuclear group of patients of the 3 diagnostic categories shall be studied simultaneously before any exposure to treatment in 6 comprehensive dimensions (neurochemistry, neuroimaging, neuromodulation, neurocognition, genomics and proteomics). They will be subsequently followed up longitudinally in the medium term. These groups findings will be compared to a control group of healthy individuals matched for demographic variables. With such strategy, we aim to identify clinical and biological markers for: early detection of individuals with an increased risk for neuropsychiatric disorders in general; discrimination between the different psychiatric diagnoses with a greater degree of specificity, shedding light on the understanding of the causal mechanisms of those three disorders; and definition of predictive indices of therapeutic response and medium-term prognosis. In addition, we will correlate the findings of alteration in each of the six dimensions investigated, aiming to identify combinations of specific markers that may guide changes in the clinical decision process. Finally, we will also explore the following lines of investigation: studies of individuals suffering from subclinical disorders and presenting sporadic psychiatric symptoms, allowing us to investigate transition stages to clarify the continuum between health and disease in the clinical and neurodiagnostic dimensions, thus affording reliable tools for the early diagnosis and the development of preventive strategies of the diseases in question; clinical studies of longitudinal follow up of healthy elderly subjects and individuals with mild cognitive impairment, testing the efficacy of innovative treatments; evaluation of molecular and biochemical changes in post-mortem brains of patients with Schizophrenia, Bipolar Disorder or Alzheimer's disease against healthy controls, in order to unravel dysregulated molecular and biochemical pathways common and distinct between major psychiatric disorders; and comparisons of central and peripheral results of humans against results of gene expression in transgenic animal models, in order to elucidate the effects of genes of risk to psychiatric disorders at the molecular level, in a translational fashion. The feasibility of such a multidimensional project demands a sophisticated organization, with top level human resources and an integrated network of laboratories of high complexity, compatible with the solid infra-structure and financing provided to the INCTs. Such structure will allow us to increment the worldwide impact of the scientific publications produced over the next few years, foster the participation of international partners in such publications, and help to generate products with potential for intellectual protection and commercialization, such as diagnostic kits or new therapeutic strategies. Besides, in a completely integrated fashion with the generation of novel scientific, knowledge, the creation of our INCT will also foster strongly activities of specialized training in our centers in Brazil and abroad, as we activities of transfer of knowledge to the society, through the dissemination of information on the research results about biomarkers in appropriate manner, by well-prepared professionals who are proficient in such kind of communication. (AU)