کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4179681 1276561 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Variation in Catechol-O-Methyltransferase Is Associated with Duloxetine Response in a Clinical Trial for Major Depressive Disorder
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Variation in Catechol-O-Methyltransferase Is Associated with Duloxetine Response in a Clinical Trial for Major Depressive Disorder
چکیده انگلیسی

BackgroundThe study objective was to evaluate variations in genes implicated in antidepressant mechanism of action for association with response to duloxetine treatment in major depressive disorder (MDD).MethodsWe assessed response over 6 weeks in 250 duloxetine-treated Caucasian patients in a randomized, double-blind study of patients with MDD. Single nucleotide polymorphisms (SNPs) were genotyped in 19 candidate genes selected based on evidence for involvement in antidepressant mechanism of action. Primary analysis examined baseline to end point reduction in the 17-item Hamilton Depression Rating Scale (HAMD17) total score, using a set-based test for association for each gene. Follow-up analyses examined individual SNPs within any significant gene for association with reduction in HAMD17 and 30-item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C-30).ResultsAfter correction for multiple comparisons, only COMT was associated with change in HAMD17 (experimentwide p = .018). Peak association was detected with rs165599 (p = .006), which accounted for approximately 3% of variance in HAMD17 change and >4% of variance in IDS-C-30 change (p = .001). The least-squared mean change (SE) in HAMD17 score by rs165599 genotype was −10.8 (1.2), −8.7 (.6), and −6.5 (.7) for patients with GG, GA, and AA genotypes, respectively. For SNPs in serotonin 2A receptor (HTR2A) previously associated with citalopram response, including rs7997012, no significant evidence of association with duloxetine response was identified.ConclusionsSingle nucleotide polymorphisms in COMT were associated with symptom change in duloxetine-treated patients with MDD. If replicated, the magnitude of the COMT genotype effect is of clinical relevance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 65, Issue 9, 1 May 2009, Pages 785–791
نویسندگان
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