Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author SOEIRO-DE-SOUZA, Marcio Gerhardt FMUSP-HC
SALVADORE, Giacomo
MORENO, Ricardo Alberto FMUSP-HC
OTADUY, Maria Concepcion Garcia FMUSP-HC
CHAIM, Kalil T. FMUSP-HC
GATTAZ, Wagner F. FMUSP-HC
ZARATE JR., Carlos A.
MACHADO-VIEIRA, Rodrigo FMUSP-HC
dc.date.issued 2013
dc.identifier.citation NEUROPSYCHOPHARMACOLOGY, v.38, n.3, p.468-475, 2013
dc.identifier.issn 0893-133X
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/2140
dc.description.abstract B-cell lymphoma 2 (Bcl-2) is an important regulator of cellular plasticity and resilience. In bipolar disorder (BD), studies have shown a key role for a Bcl-2 gene single-nucleotide polymorphism (SNP) rs956572 in the regulation of intracellular calcium (Ca2+) dynamics, Bcl-2 expression/levels, and vulnerability to cellular apoptosis. At the same time, Bcl-2 decreases glutamate (Glu) toxicity in neural cells. Abnormalities in Glu function have been implicated in BD. In magnetic resonance spectroscopy (MRS) studies, anterior cingulated cortex (ACC) Glu levels have been reported to be increased in bipolar depression and mania, but no study specifically evaluated ACC Glu levels in BD-euthymia. Here, we compared ACC Glu levels in BD-euthymia compared with healthy subjects using H-1-MRS and also evaluated the selective role of the rs956572 Bcl-2 SNP in modulating ACC Glu and Glx (sum of Glu and glutamine) in euthymic-BD. Forty euthymic subjects with BD type 1 and forty healthy controls aged 18-40 were evaluated. All participants were genotyped for Bcl-2 rs956572 and underwent a 3-Tesla brain magnetic resonance imaging examination including the acquisition of an in vivo PRESS single voxel (2 cm(3)) H-1-MRS sequence to obtain metabolite levels from the ACC. Euthymic-BD subjects had higher Glu/Cre (creatine) and Glx/Cre compared with healthy controls. The Bcl-2 SNP AA genotype was associated with elevated ACC Glu/Cre and Glx/Cre ratio in the BD group but not in controls. The present study reports for the first time an increase in ACC Glu/Cre and Glx/Cre ratios in BD-euthymia. Also, Bcl-2 AA genotype, previously associated with lower Bcl-2 expression and increase intracellular Ca2+, showed to be associated with increased ACC Glu and Glx levels in euthymic-BD subjects. The present findings reinforce a key role for glutamatergic system dysfunction in the pathophysiology of BD, potentially involving modulatory effects by Bcl-2 in the ACC. Neuropsychopharmacology (2013) 38, 468-475; doi:10.1038/npp.2012.203; published online 17 October 2012
dc.description.sponsorship · Sao Paulo Research Foundation (FAPESP)
· Research Foundation Support Agency of the State of Sao Paulo, Brazil (FAPESP)
· Brain & Behavior Research Foundation Award (NARSAD)
dc.language.iso eng
dc.publisher NATURE PUBLISHING GROUP
dc.relation.ispartof Neuropsychopharmacology
dc.rights restrictedAccess
dc.subject Bcl-2; bipolar disorder; depression; calcium; glutamate; spectroscopy
dc.subject.other subgenual prefrontal cortex; amino-acid-concentrations; mood disorders; depressed-patients; major depression; rating-scale; lithium; receptor; abnormalities; protein
dc.title Bcl-2 rs956572 Polymorphism is Associated with Increased Anterior Cingulate Cortical Glutamate in Euthymic Bipolar I Disorder
dc.type article
dc.rights.holder Copyright NATURE PUBLISHING GROUP
dc.description.group LIM/27
dc.description.group LIM/44
dc.description.group LIM/05
dc.description.group LIM/23
dc.identifier.doi 10.1038/npp.2012.203
dc.identifier.pmid 23072837
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author SOEIRO-DE-SOUZA, Marcio Gerhardt:FM:
hcfmusp.author MORENO, Ricardo Alberto:HC:IPQ
hcfmusp.author OTADUY, Maria Concepcion Garcia:HC:INRAD
hcfmusp.author CHAIM, Kalil T.:HC:INRAD
hcfmusp.author GATTAZ, Wagner F.:FM:MPS
hcfmusp.author MACHADO-VIEIRA, Rodrigo:HC:LIM/27
hcfmusp.author.external · SALVADORE, Giacomo:NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA
· ZARATE JR., Carlos A.:NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA
hcfmusp.origem.id 2-s2.0-84872489243
hcfmusp.origem.id WOS:000313771000010
hcfmusp.publisher.city LONDON
hcfmusp.publisher.country ENGLAND
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dc.description.index MEDLINE
hcfmusp.citation.scopus 30
hcfmusp.citation.wos 26
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Estados Unidos


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