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A monoamine oxidase B gene variant and short-term antidepressant treatment response
Authors:Tadić André  Rujescu Dan  Müller Matthias J  Kohnen Ralf  Stassen Hans H  Dahmen Norbert  Szegedi Armin
Institution:Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, 55131 Mainz, Germany. tadic@uni-mainz.de
Abstract:Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized double-blind controlled clinical trial, conducted at 50 centers in Germany, comparing the efficacy of mirtazapine and paroxetine during 6 weeks of treatment. Overall, female patients homozygous for the A-allele had a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remained statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period were constantly and markedly lower, but not statistically different. In males, we found no association between the MAOB A644G intron 13 SNP and antidepressant treatment response. Our data provide first suggestive evidence that the MAOB A644G SNP is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. To confirm the role of the MAOB A644G gene variant in antidepressant treatment response, independent replications are needed. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression.
Keywords:5-HT" target="_blank">5-HT  serotonin  5-HTT" target="_blank">5-HTT  serotonin transporter  ANOVA" target="_blank">ANOVA  analysis of variance  bp" target="_blank">bp  base-pair  CEU-CEPH" target="_blank">CEU-CEPH  Utah residents with ancestry from northern and western Europe  CGI" target="_blank">CGI  Clinical Global Impressions Scale  CI" target="_blank">CI  95%-confidence interval  COMT" target="_blank">COMT  catechol-O-methyltransferase (gene)  DA" target="_blank">DA  dopamine  DNA" target="_blank">DNA  Deoxyribonucleic acid  DSM-IV" target="_blank">DSM-IV  Diagnostic and Statistical Manual of Mental Disorders  4th Edition  HAMD-17" target="_blank">HAMD-17  Hamilton Rating Scale for Depression  17-item version  HTTLPR" target="_blank">HTTLPR  Serotonin transporter gene-linked polymorphic region  ITT" target="_blank">ITT  intention-to-treat  LD" target="_blank">LD  linkage disequilibrium  MADRS" target="_blank">MADRS  Montgomery–Asberg Depression Rating Scale  MAOA" target="_blank">MAOA  monoamine oxidase A (gene)  MAO-A" target="_blank">MAO-A  monoamine oxidase A (enzyme)  MAOB" target="_blank">MAOB  monoamine oxidase B (gene)  MAO-B" target="_blank">MAO-B  monoamine oxidase B (enzyme)  MD" target="_blank">MD  Major Depression  MDE" target="_blank">MDE  major depressive episode  M" target="_blank">M  I  N  I    Mini-International Neuropsychiatric Interview  MMRM" target="_blank">MMRM  mixed-effects model repeated measures  mRNA" target="_blank">mRNA  messenger Ribonucleic Acid  n" target="_blank">n  number  NE" target="_blank">NE  Norepinephrine  OR" target="_blank">OR  Odds Ratio  PCR" target="_blank">PCR  Polymerase chain reaction  PD" target="_blank">PD  Parkinson’s disease  SNP" target="_blank">SNP  single nucleotide polymorphism  SPSS" target="_blank">SPSS  Statistical Package for the Social Sciences  SSRI" target="_blank">SSRI  selective serotonin reuptake inhibitor
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