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NEUROBIOLOGICAL DIFFERENCES BETWEEN TREATMENT-NAIVE PATIENTS WITH BIPOLAR DISORDER SUBTYPES I AND II

Grant number: 13/03905-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2013
Effective date (End): May 31, 2016
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Geraldo Busatto Filho
Grantee:Marcus Vinicius Zanetti
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In spite of its high prevalence and clinical severity, the neurobiological basis of type II bipolar disorder (BD) is still relatively understudied. The study of the types I and II subtypes of BD would allow us to identify biological markers (endophenotypes) of diagnosis and treatment-response, besides improving our knowledge about the underlying pathophysiology of its clinical manifestations. We sought to study treatment-naïve patients with the types I and II subtypes of BD combining neuroimaging (structural MRI and diffusion tensor imaging), neurocognitive assessment, measurement of brain-derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF) levels in the serum, and expression and activity of the glycogen synthase kinase 3 ² (GSK3-²) enzyme in platelets. A group of healthy volunteers matched for age, gender and socioeconomic status will also be studied. A high-dimensional and multivariate classifier will be generated based on all obtained measures aiming to identify the pattern of neurobiological features that better separate the groups under study (i.e., BD type I, BD type II and controls). Measures of diagnostic performance will also be calculated (sensitivity, specificity, positive predictive value, negative predictive value and area under the ROC curve).

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Scientific publications (15)
(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)
CHING, CHRISTOPHER R. K.; HIBAR, DERREK P.; GURHOLT, TIRIL P.; NUNES, ABRAHAM; THOMOPOULOS, SOPHIA I.; ABE, CHRISTOPH; AGARTZ, INGRID; BROUWER, RACHEL M.; CANNON, DARA M.; DE ZWARTE, SONJA M. C.; et al. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group. Human Brain Mapping, v. 43, n. 1, SI, p. 56-82, . (10/18672-7, 13/03905-4, 09/14891-9, 12/23796-2)
CHING, CHRISTOPHER R. K.; HIBAR, DERREK P.; GURHOLT, TIRIL P.; NUNES, ABRAHAM; THOMOPOULOS, SOPHIA I.; ABE, CHRISTOPH; AGARTZ, INGRID; BROUWER, RACHEL M.; CANNON, DARA M.; DE ZWARTE, SONJA M. C.; et al. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group. Human Brain Mapping, . (10/18672-7, 12/23796-2, 13/03905-4, 09/14891-9)
JOAQUIM, HELENA P. G.; ZANETTI, MARCUS V.; SERPA, MAURICIO H.; VAN DE BILT, MARTINUS T.; SALLET, PAULO C.; CHAIM, TIFFANY M.; BUSATTO, GERALDO F.; GATTAZ, WAGNER F.; TALIB, LEDA L.. Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis. SCHIZOPHRENIA RESEARCH, v. 195, p. 402-405, . (13/03905-4, 13/10350-9)
HIBAR, D. P.; WESTLYE, L. T.; DOAN, N. T.; JAHANSHAD, N.; CHEUNG, J. W.; CHING, C. R. K.; VERSACE, A.; BILDERBECK, A. C.; UHLMANN, A.; MWANGI, B.; et al. Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. MOLECULAR PSYCHIATRY, v. 23, n. 4, p. 932-942, . (12/23796-2, 10/18672-7, 13/03905-4, 09/14891-9)
FAVRE, PAULINE; PAULING, MELISSA; STOUT, JACQUES; HOZER, FRANZ; SARRAZIN, SAMUEL; ABE, CHRISTOPH; ALDA, MARTIN; ALLOZA, CLARA; ALONSO-LANA, SILVIA; ANDREASSEN, OLE A.; et al. Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals. NEUROPSYCHOPHARMACOLOGY, v. 44, n. 13, p. 2285-2293, . (10/18672-7, 12/23796-2, 13/03905-4, 09/14891-9)
ZANETTI, MARCUS V.; OTADUY, MARIA C.; DE SOUSA, RAFAEL T.; GATTAZ, WAGNER F.; BUSATTO, GERALDO F.; LEITE, CLAUDIA C.; MACHADO-VIEIRA, RODRIGO. Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 18, n. 6, . (13/03905-4, 09/14891-9)
CHAIM-AVANCINI, T. M.; DOSHI, J.; ZANETTI, M. V.; ERUS, G.; SILVA, M. A.; DURAN, F. L. S.; CAVALLET, M.; SERPA, M. H.; CAETANO, S. C.; LOUZA, M. R.; et al. Neurobiological support to the diagnosis of ADHD in stimulant-naive adults: pattern recognition analyses of MRI data. ACTA PSYCHIATRICA SCANDINAVICA, v. 136, n. 6, p. 623-636, . (13/03905-4)
LOCH, ALEXANDRE A.; ZANETTI, MARCUS V.; DE SOUSA, RAFAEL T.; CHAIM, TIFFANY M.; SERPA, MAURICIO H.; GATTAZ, WAGNER F.; TEIXEIRA, ANTONIO L.; MACHADO-VIEIRA, RODRIGO. Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 56, p. 243-246, . (13/03905-4, 09/14891-9)
HAN, LAURA K. M.; DINGA, RICHARD; HAHN, TIM; CHING, CHRISTOPHER R. K.; EYLER, LISA T.; AFTANAS, LYUBOMIR; AGHAJANI, MOJI; ALEMAN, ANDRE; BAUNE, BERNHARD T.; BERGER, KLAUS; et al. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group. MOLECULAR PSYCHIATRY, v. 26, n. 9, p. 16-pg., . (13/03905-4)
SERPA, MAURICIO H.; OU, YANGMING; SCHAUFELBERGER, MARISTELA S.; DOSHI, JIMIT; FERREIRA, LUIZ K.; MACHADO-VIEIRA, RODRIGO; MENEZES, PAULO R.; SCAZUFCA, MARCIA; DAVATZIKOS, CHRISTOS; BUSATTO, GERALDO F.; et al. Neuroanatomical Classification in a Population-Based Sample of Psychotic Major Depression and Bipolar I Disorder with 1 Year of Diagnostic Stability. BIOMED RESEARCH INTERNATIONAL, . (13/03905-4)
SERPA, MAURICIO H.; OU, YANGMING; SCHAUFELBERGER, MARISTELA S.; DOSHI, JIMIT; FERREIRA, LUIZ K.; MACHADO-VIEIRA, RODRIGO; MENEZES, PAULO R.; SCAZUFCA, MARCIA; DAVATZIKOS, CHRISTOS; BUSATTO, GERALDO F.; et al. Neuroanatomical Classification in a Population-Based Sample of Psychotic Major Depression and Bipolar I Disorder with 1 Year of Diagnostic Stability. BIOMED RESEARCH INTERNATIONAL, v. 2014, p. 9-pg., . (13/03905-4)
EYLER, LISA; TIMMONS, GARRETT; BAUNE, BERNHARD; BUSATTO, GERALDO; CASERAS, XAVIER; DANNLOWSKI, UDO; GROTEGERD, DOMINIK; HAHN, TIM; HAJEK, TOMAS; HOUENOU, JOSSELIN; et al. Advanced Brain Age and its Clinical Correlates in Bipolar Disorder: A Global, Multi-Site Analysis of Data From the ENIGMA Bipolar Disorders Working Group. BIOLOGICAL PSYCHIATRY, v. 85, n. 10, p. 1-pg., . (13/03905-4)
DE MOURA, MARIANA T. M.; ZANETTI, MARCUS V.; DURAN, FABIO L. S.; SCHAUFELBERGER, MARISTELA S.; MENEZES, PAULO R.; SCAZUFCA, MARCIA; BUSATTO, GERALDO F.; SERPA, MAURICIO H.. Corpus callosum volumes in the 5 years following the first-episode of schizophrenia: Effects of antipsychotics, chronicity and maturation. NEUROIMAGE-CLINICAL, v. 18, p. 932-942, . (13/03905-4, 14/00481-1)
GERMANN, JUERGEN; GOUVEIA, FLAVIA VENETUCCI; MARTINEZ, RAQUEL C. R.; ZANETTI, MARCUS VINICIUS; DE SOUZA DURAN, FABIO LUIS; CHAIM-AVANCINI, TIFFANY M.; SERPA, MAURICIO H.; CHAKRAVARTY, M. MALLAR; DEVENYI, GABRIEL A.. Fully Automated Habenula Segmentation Provides Robust and Reliable Volume Estimation Across Large Magnetic Resonance Imaging Datasets, Suggesting Intriguing Developmental Trajectories in Psychiatric Disease. BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING, v. 5, n. 9, p. 7-pg., . (09/14891-9, 13/03905-4, 10/18672-7, 12/23796-2)
ZANETTI, MARCUS V.; MACHADO-VIEIRA, RODRIGO; JOAQUIM, HELENA P. G.; CHAIM, TIFFANY M.; SERPA, MAURICIO H.; DE SOUSA, RAFAEL T.; GATTAZ, WAGNER F.; BUSATTO, GERALDO F.; TALIB, LEDA L.. Distinct Glycogen Synthase Kinase 3 beta and Phospholipase A2 Expression Profiles in Bipolar I and II Disorders. BIOLOGICAL PSYCHIATRY, v. 79, n. 9, p. 2-pg., . (13/03905-4)

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