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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)

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Scientific publications (19)
(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)
LOCH, ALEXANDRE ANDRADE; MOTA, NATALIA BEZERRA; ROESSLER, WULF; GATTAZ, WAGNER FARID. Exacerbation of psychosis risk during the COVID-19 pandemic: The disproportionate impact on the lower income population. PSYCHIATRY RESEARCH, v. 307, JAN 2022. Web of Science Citations: 0.
TALIB, LEDA L.; COSTA, ALANA C.; JOAQUIM, HELENA P. G.; PEREIRA, CICERO A. C.; VAN DE BILT, MARTINUS T.; LOCH, ALEXANDRE A.; GATTAZ, WAGNER F. Increased PLA(2) activity in individuals at ultra-high risk for psychosis. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 271, n. 8, p. 1593-1599, DEC 2021. Web of Science Citations: 0.
DE-PAULA, V. J.; FORLENZA, V, O. Lithium modulates multiple tau kinases with distinct effects in cortical and hippocampal neurons according to concentration ranges. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 395, n. 1 NOV 2021. Web of Science Citations: 0.
JOAQUIM, HELENA P. G.; COSTA, ALANA C.; PEREIRA, CICERO A. C.; TALIB, LEDA L.; BILT, V, MARTINUS M.; LOCH, ALEXANDRE A.; GATTAZ, WAGNER F. lasmatic endocannabinoids are decreased in subjects with ultra-high risk of psychosi. European Journal of Neuroscience, v. 55, n. 4, SI NOV 2021. Web of Science Citations: 1.
STELLA, FLORINDO; PAIS, V, MARCOS; LOUREIRO, JULIA C.; RADANOVIC, MARCIA; FORLENZA, V, ORESTES. Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C). PSYCHOGERIATRICS, OCT 2021. Web of Science Citations: 0.
CECCHINI, MARIO AMORE; YASSUDA, MONICA SANCHES; SQUARZONI, PAULA; COUTINHO, ARTUR MARTINS; FARIA, DANIELE DE PAULA; DE SOUZA DURAN, FABIO LUIZ; DA COSTA, NAOMI ANTUNES; DE GOBBI PORTO, FABIO HENRIQUE; NITRINI, RICARDO; FORLENZA, ORESTES VICENTE; DOZZI BRUCKI, SONIA MARIA; BUCHPIGUEL, CARLOS ALBERTO; PARRA, MARIO A.; BUSATTO, GERALDO F. Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum. BRAIN AND COGNITION, v. 152, AUG 2021. Web of Science Citations: 0.
SAJATOVIC, MARTHA; DOLS, ANNEMIEK; REJ, SOHAM; ALMEIDA, OSVALDO P.; BEUNDERS, ALEXANDRA J. M.; BLUMBERG, HILARY P.; BRIGGS, FARREN B. S.; FORESTER, BRENT P.; PATRICK, REGAN E.; FORLENZA, V, ORESTES; GILDENGERS, ARIEL; JIMENEZ, ESTHER; VIETA, EDUARD; MULSANT, BENOIT; SCHOUWS, SIGFRIED; PAANS, NADINE; STREJILEVICH, SERGIO; SUTHERLAND, ASHLEY; TSAI, SHANGYING; WILSON, BETSY; EYLER, LISA T. Bipolar symptoms, somatic burden, and functioning in older-age bipolar disorder: Analyses from the Global Aging & Geriatric Experiments in Bipolar Disorder Database project. BIPOLAR DISORDERS, AUG 2021. Web of Science Citations: 0.
FELIPE DA SILVA, RENATA DE MELO; BRUNONI, ANDRE R.; GOERIGK, STEPHAN; BATISTUZZO, MARCELO CAMARGO; DA CONCEICAO COSTA, DANIEL LUCAS; DINIZ, JULIANA BELO; PADBERG, FRANK; D'URSO, GIORDANO; MIGUEL, EURIPEDES CONSTANTINO; SHAVITT, ROSELI GEDANKE. Efficacy and safety of transcranial direct current stimulation as an add-on treatment for obsessive-compulsive disorder: a randomized, sham-controlled trial. NEUROPSYCHOPHARMACOLOGY, v. 46, n. 5 JAN 2021. Web of Science Citations: 0.
ROCHA, NICOLE KEMBERLY R.; THEMOTEO, RAFAEL; BRENTANI, HELENA; FORLENZA, ORESTES V.; DE PAULA, VANESSA DE JESUS RODRIGUES. Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways. FRONTIERS IN NEUROSCIENCE, v. 14, DEC 1 2020. Web of Science Citations: 0.
PAIS, MARCOS; MARTINEZ, LUANA; RIBEIRO, OCTAVIO; LOUREIRO, JULIA; FERNANDEZ, ROMEL; VALIENGO, LEANDRO; CANINEU, PAULO; STELLA, FLORINDO; TALIB, LEDA; RADANOVIC, MARCIA; FORLENZA, V, ORESTES. Early diagnosis and treatment of Alzheimer's disease: new definitions and challenges. Revista Brasileira de Psiquiatria, v. 42, n. 4, p. 431-441, JUL-AUG 2020. Web of Science Citations: 3.
JOAQUIM, HELENA P. G.; COSTA, ALANA C.; TALIB, LEDA L.; DETHLOFF, FREDERIK; SERPA, MAURICIO H.; ZANETTI, V, MARCUS; VAN DE BILT, MARTINUS; TURCK, CHRISTOPH W. Plasma Metabolite Profiles in First Episode Psychosis: Exploring Symptoms Heterogeneity/Severity in Schizophrenia and Bipolar Disorder Cohorts. FRONTIERS IN PSYCHIATRY, v. 11, JUN 5 2020. Web of Science Citations: 0.
COSTA, ALANA C.; JOAQUIM, HELENA P. G.; FORLENZA, V, ORESTES; GATTAZ, WAGNER F.; TALIB, LEDA L. Three plasma metabolites in elderly patients differentiate mild cognitive impairment and Alzheimer's disease: a pilot study. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 270, n. 4, p. 483-488, JUN 2020. Web of Science Citations: 0.
JOAQUIM, HELENA P. G.; COSTA, ALANA CAROLINE; SERPA, MAURICIO HENRIQUES; TALIB, LEDA L.; GATTAZ, WAGNER F. Reduced Annexin A3 in schizophrenia. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 270, n. 4, p. 489-494, JUN 2020. Web of Science Citations: 0.
MARCOS PAIS; LUANA MARTINEZ; OCTÁVIO RIBEIRO; JÚLIA LOUREIRO; ROMEL FERNANDEZ; LEANDRO VALIENGO; PAULO CANINEU; FLORINDO STELLA; LEDA TALIB; MARCIA RADANOVIC; ORESTES V. FORLENZA. Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Revista Brasileira de Psiquiatria, n. ahead, p. -, 2020.
MARCOS PAIS; LUANA MARTINEZ; OCTÁVIO RIBEIRO; JÚLIA LOUREIRO; ROMEL FERNANDEZ; LEANDRO VALIENGO; PAULO CANINEU; FLORINDO STELLA; LEDA TALIB; MARCIA RADANOVIC; ORESTES V. FORLENZA. Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Revista Brasileira de Psiquiatria, v. 42, n. 4, p. 431-441, Ago. 2020.
SQUARZONI, PAULA; FARIA, DANIELE DE PAULA; YASSUDA, MONICA SANCHES; DE GOBBI PORTO, FABIO HENRIQUE; COUTINHO, ARTUR MARTINS; DA COSTA, NAOMI ANTUNES; NITRINI, RICARDO; FORLENZA, ORESTES VICENTE; DE SOUZA DURAN, FABIO LUIZ; DOZZI BRUCKI, SONIA MARIA; BUCHPIGUEL, CARLOS ALBERTO; BUSATTO, GERALDO F. Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects. JOURNAL OF ALZHEIMER'S DISEASE, v. 78, n. 1, p. 229-244, 2020. Web of Science Citations: 0.
BUSATTO, GERALDO F.; DE GOBBI PORTO, FABIO HENRIQUE; FARIA, DANIELE DE PAULA; SQUARZONI, PAULA; COUTINHO, ARTUR MARTINS; GARCEZ, ALEXANDRE TELES; PENTEADO ROSA, PEDRO GOMES; DA COSTA, NAOMI ANTUNES; CARVALHO, CLEUDIANA LIMA; TORRALBO, LETICIA; DE ALMEIDA HERNANDES, JULLIE ROSANA; ONO, CARLA RACHEL; DOZZI BRUCKI, SONIA MARIA; NITRINI, RICARDO; BUCHPIGUEL, CARLOS ALBERTO; SOUZA DURAN, FABIO LUIS; FORLENZA, ORESTES VICENTE. In vivo imaging evidence of poor cognitive resilience to Alzheimer's disease pathology in subjects with very low cognitive reserve from a low-middle income environment. ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING, v. 12, n. 1 2020. Web of Science Citations: 2.
HELENA P. G. JOAQUIM; ALANA C. COSTA; ORESTES V. FORLENZA; WAGNER F. GATTAZ; LEDA L. TALIB. Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer's disease patients. ARCHIVES OF CLINICAL PSYCHIATRY, v. 46, n. 5, p. 120-124, Out. 2019. Web of Science Citations: 0.
JOAQUIM, HELENA P. G.; COSTA, ALANA C.; GATTAZ, WAGNER F.; TALIB, LEDA LEME. Kynurenine is correlated with IL-1 beta in plasma of schizophrenia patients. JOURNAL OF NEURAL TRANSMISSION, v. 125, n. 5, SI, p. 869-873, MAY 2018. Web of Science Citations: 2.

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