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SPECGENE: genetic association study between single nucleotide polymorphisms of GAD1 and reelin and magnetic ressonance spectroscopy in bipolar I

Abstract

The pathophysiological mechanisms of bipolar disorder are not completely clarified and several hypothesis have already been formulated including the role of monoamines, gama amino butiric acid (GABA) and glutamate. GABA is the main inhibitory neurotransmitter while glutamate is the main excitatory neurotransmitter. Genes that play a role in GABA metabolism and in the activity of GABA neurons are very important to understand the GABA function, once they affect neurodevelopment and its dysfunctions may predispose to neuropsychiatric diseases. The two genes that are going to be study in this project are glutamic acid descarboxilase (GAD1) and reelin (Reln). The enzyme glutamic acid descarboxilase (GAD67) metabolizes glutamate in GABA in the pre synaptic neuronal regions and is coded by the gene GAD1. Reelin is secretory serine protease with dual roles in mammalian brain: embryologically, it guides neurons and radial glial cells to their corrected positions in the developing brain; in adult brain, Reelin is involved in a signaling pathway which underlies neurotransmission, memory formation and synaptic plasticity. Magnetic resonance spectroscopy (MRS) studies on bipolar disorder show a number of alterations in cerebral level of GABA and glutamate in different cerebral areas when compared to healthy subjects and other mood disorders. Objetive: Investigate in bipolar patients and helathy controls the association of GAD1 and Reln single nucleotide polymorphisms(SNP) and cerebral levels of GABA/glutamate on MRS. Methods: 70 symptomatic bipolar I patients medication free and 70 healthy controls are going to be genotyped for GAD1 and Reln SNPs and GABA/glutamate MRS.Key words: GAD1, GAD67, bipolar, GABA, Glutamate, Reelin, Rln, Spectroscopy. (AU)

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Scientific publications (5)
(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.; EYLER, LISA T.; FAVRE, PAULINE; HAJEK, TOMAS; HAUKVIK, UNN K.; HOUENOU, JOSSELIN; LANDEN, MIKAEL; LETT, TRISTRAM A.; MCDONALD, COLM; NABULSI, LEILA; PATEL, YASH; PAULING, MELISSA E.; PAUS, TOMAS; RADUA, JOAQUIM; SOEIRO-DE-SOUZA, MARCIO G.; TRONCHIN, GIULIA; VAN HAREN, NEELTJE E. M.; VIETA, EDUARD; WALTER, HENRIK; ZENG, LING-LI; ALDA, MARTIN; ALMEIDA, JORGE; ALNAES, DAG; ALONSO-LANA, SILVIA; ALTIMUS, CARA; BAUER, MICHAEL; BAUNE, BERNHARD T.; BEARDEN, CARRIE E.; BELLANI, MARCELLA; BENEDETTI, FRANCESCO; BERK, MICHAEL; BILDERBECK, AMY C.; BLUMBERG, HILARY P.; BOEN, ERLEND; BOLLETTINI, IRENE; DEL MAR BONNIN, CATERINA; BRAMBILLA, PAOLO; CANALES-RODRIGUEZ, ERICK J.; CASERAS, XAVIER; DANDASH, ORWA; DANNLOWSKI, UDO; DELVECCHIO, GIUSEPPE; DIAZ-ZULUAGA, ANA M.; DIMA, DANAI; DUCHESNAY, EDOUARD; ELVSASHAGEN, TORBJORN; FEARS, SCOTT C.; FRANGOU, SOPHIA; FULLERTON, JANICE M.; GLAHN, DAVID C.; GOIKOLEA, JOSE M.; GREEN, MELISSA J.; GROTEGERD, DOMINIK; GRUBER, OLIVER; HAARMAN, BARTHOLOMEUS C. M.; HENRY, CHANTAL; HOWELLS, FLEUR M.; IVES-DELIPERI, VICTORIA; JANSEN, ANDREAS; KIRCHER, TILO T. J.; KNOECHEL, CHRISTIAN; KRAMER, BERND; LAFER, BENY; LOPEZ-JARAMILLO, CARLOS; MACHADO-VIEIRA, RODRIGO; MACINTOSH, BRADLEY J.; MELLONI, ELISA M. T.; MITCHELL, PHILIP B.; NENADIC, IGOR; NERY, FABIANO; NUGENT, ALLISON C.; OERTEL, VIOLA; OPHOFF, ROEL A.; OTA, MIHO; OVERS, BRONWYN J.; PHAM, DANIEL L.; PHILLIPS, MARY L.; PINEDA-ZAPATA, JULIAN A.; POLETTI, SARA; POLOSAN, MIRCEA; POMAROL-CLOTET, EDITH; POUCHON, ARNAUD; QUIDE, YANN; RIVE, MARIA M.; ROBERTS, GLORIA; RUHE, HENRICUS G.; SALVADOR, RAYMOND; SARRO, SALVADOR; SATTERTHWAITE, THEODORE D.; SCHENE, AART H.; SIM, KANG; SOARES, JAIR C.; STAEBLEIN, MICHAEL; STEIN, DAN J.; TAMNES, CHRISTIAN K.; THOMAIDIS, GEORGIOS V.; UPEGUI, CRISTIAN VARGAS; VELTMAN, DICK J.; WESSA, MICHELE; WESTLYE, LARS T.; WHALLEY, HEATHER C.; WOLF, DANIEL H.; WU, MON-JU; YATHAM, LAKSHMI N.; ZARATE, CARLOS A.; THOMPSON, PAUL M.; ANDREASSEN, OLE A.; WOR, ENIGMA BIPOLAR DISORDER. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group. Human Brain Mapping, JUL 2020. Web of Science Citations: 0.
FAVRE, PAULINE; PAULING, MELISSA; STOUT, JACQUES; HOZER, FRANZ; SARRAZIN, SAMUEL; ABE, CHRISTOPH; ALDA, MARTIN; ALLOZA, CLARA; ALONSO-LANA, SILVIA; ANDREASSEN, OLE A.; BAUNE, BERNHARD T.; BENEDETTI, FRANCESCO; BUSATTO, GERALDO F.; CANALES-RODRIGUEZ, ERICK J.; CASERAS, XAVIER; CHAIM-AVANCINI, TIFFANY MOUKBEL; CHING, CHRISTOPHER R. K.; DANNLOWSKI, UDO; DEPPE, MICHAEL; EYLER, LISA T.; FATJO-VILAS, MAR; FOLEY, SONYA F.; GROTEGERD, DOMINIK; HAJEK, TOMAS; HAUKVIK, UNN K.; HOWELLS, FLEUR M.; JAHANSHAD, NEDA; KUGEL, HARALD; LAGERBERG, TRINE V.; LAWRIE, STEPHEN M.; LINKE, JULIA O.; MCINTOSH, ANDREW; MELLONI, ELISA M. T.; MITCHELL, PHILIP B.; POLOSAN, MIRCEA; POMAROL-CLOTET, EDITH; REPPLE, JONATHAN; ROBERTS, GLORIA; ROOS, ANNERINE; ROSA, PEDRO G. P.; SALVADOR, RAYMOND; SARRO, SALVADOR; SCHOFIELD, PETER R.; SERPA, MAURICIO H.; SIM, KANG; STEIN, DAN J.; SUSSMANN, JESS E.; TEMMINGH, HENK S.; THOMPSON, PAUL M.; VERDOLINI, NORMA; VIETA, EDUARD; WESSA, MICHELE; WHALLEY, HEATHER C.; ZANETTI, MARCUS V.; LEBOYER, MARION; MANGIN, JEAN-FRANCOIS; HENRY, CHANTAL; DUCHESNAY, EDOUARD; HOUENOU, JOSSELIN; WORKING, ENIGMA BIPOLAR DISORDER. 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, DEC 2019. Web of Science Citations: 1.
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.; KRAEMER, B.; OVERS, B.; HARTBERG, C. B.; ABE, C.; DIMA, D.; GROTEGERD, D.; SPROOTEN, E.; BOEN, E.; JIMENEZ, E.; HOWELLS, F. M.; DELVECCHIO, G.; TEMMINGH, H.; STARKE, J.; ALMEIDA, J. R. C.; GOIKOLEA, J. M.; HOUENOU, J.; BEARD, L. M.; RAUER, L.; ABRAMOVIC, L.; BONNIN, M.; PONTEDURO, M. F.; KEIL, M.; RIVE, M. M.; YAO, N.; YALIN, N.; NAJT, P.; ROSA, P. G.; REDLICH, R.; TROST, S.; HAGENAARS, S.; FEARS, S. C.; ALONSO-LANA, S.; VAN ERP, T. G. M.; NICKSON, T.; CHAIM-AVANCINI, T. M.; MEIER, T. B.; ELVSASHAGEN, T.; HAUKVIK, U. K.; LEE, W. H.; SCHENE, A. H.; LLOYD, A. J.; YOUNG, A. H.; NUGENT, A.; DALE, A. M.; PFENNIG, A.; MCINTOSH, A. M.; LAFER, B.; BAUNE, B. T.; EKMAN, C. J.; ZARATE, C. A.; BEARDEN, C. E.; HENRY, C.; SIMHANDL, C.; MCDONALD, C.; BOURNE, C.; STEIN, D. J.; WOLF, D. H.; CANNON, D. M.; GLAHN, D. C.; VELTMAN, D. J.; POMAROL-CLOTET, E.; VIETA, E.; CANALES-RODRIGUEZ, E. J.; NERY, F. G.; DURAN, F. L. S.; BUSATTO, G. F.; ROBERTS, G.; PEARLSON, G. D.; GOODWIN, G. M.; KUGEL, H.; WHALLEY, H. C.; RUHE, H. G.; SOARES, J. C.; FULLERTON, J. M.; RYBAKOWSKI, J. K.; SAVITZ, J.; CHAIM, K. T.; FATJO-VILAS, M.; SOEIRO-DE-SOUZA, M. G.; BOKS, M. P.; ZANETTI, M. V.; OTADUY, M. C. G.; SCHAUFELBERGER, M. S.; ALDA, M.; INGVAR, M.; PHILLIPS, M. L.; KEMPTON, M. J.; BAUER, M.; LANDEN, M.; LAWRENCE, N. S.; VAN HAREN, N. E. M.; HORN, N. R.; FREIMER, N. B.; GRUBER, O.; SCHOFIELD, P. R.; MITCHELL, P. B.; KAHN, R. S.; LENROOT, R.; MACHADO-VIEIRA, R.; OPHOFF, R. A.; SARRO, S.; FRANGOU, S.; SATTERTHWAITE, T. D.; HAJEK, T.; DANNLOWSKI, U.; MALT, U. F.; AROLT, V.; GATTAZ, W. F.; DREVETS, W. C.; CASERAS, X.; AGARTZ, I.; THOMPSON, P. M.; ANDREASSEN, O. A.; WORKING, ENIGMA BIPOLAR DISORDER. 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, APR 2018. Web of Science Citations: 88.
SOEIRO-DE-SOUZA, M. G.; LAFER, B.; MORENO, R. A.; NERY, F. G.; CHILE, T.; CHAIM, K.; DA COSTA LEITE, C.; MACHADO-VIEIRA, R.; OTADUY, M. C. G.; VALLADA, H. The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder. TRANSLATIONAL PSYCHIATRY, v. 7, APR 11 2017. Web of Science Citations: 2.
SOEIRO-DE-SOUZA, MARCIO GERHARDT; PASTORELLO, BRUNO F.; LEITE, CLAUDIA DA COSTA; HENNING, ANKE; MORENO, RICARDO A.; GARCIA OTADUY, MARIA CONCEPCION. Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: H-1-MRS Study. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, v. 19, n. 8 AUG 2016. Web of Science Citations: 12.

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