Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Int J Neuropsychopharmacol ; 13(6): 715-24, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20047709

RESUMO

In a previous study we showed that genetic variation in HTR2A, which encodes the serotonin 2A receptor, influenced outcome of citalopram treatment in patients with major depressive disorder. Since chronic administration of citalopram, which selectively and potently inhibits the serotonin transporter (5-HTT), putatively enhances serotonergic transmission, it is conceivable that genetic variation within HTR2A also influences pretreatment 5-HTT function or serotonergic transmission. The present study used positron emission tomography (PET) and the selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker alleles that predict treatment outcome also predict differences in 5-HTT binding. Brain levels of 5-HTT were assessed in vivo using PET measures of the non-displaceable component of the [11C]DASB binding potential (BPND). DNA from 43 patients and healthy volunteers, all unmedicated, was genotyped with 14 single nucleotide polymorphisms located within or around HTR2A. Allelic association with BPND was assessed in eight brain regions, with covariates to control for race and ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and three markers in a region spanning the 3' untranslated region and second intron of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069). The association signal at rs7333412 remained significant (p<0.05) after applying corrections for multiple testing via permutation. Genetic variation in HTR2A that was previously associated with citalopram treatment outcome was also associated with thalamic 5-HTT binding. While further work is needed to identify the actual functional genetic variants involved, these results suggest that a relationship exists between genetic variation in HTR2A and either 5-HTT expression or central serotonergic transmission that influences the therapeutic response to 5-HTT inhibition in major depression.


Assuntos
Benzilaminas/metabolismo , Transtorno Bipolar , Transtorno Depressivo Maior , Polimorfismo de Nucleotídeo Único/genética , Tomografia por Emissão de Pósitrons , Receptor 5-HT2A de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adulto , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Mapeamento Encefálico , Radioisótopos de Carbono , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ligação Proteica/genética , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa