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https://hdl.handle.net/2440/96424
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Type: | Journal article |
Title: | Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans |
Author: | Wong, M. Dong, C. Flores, D. Ehrhart-Bornstein, M. Bornstein, S. Arcos-Burgos, M. Licinio, J. |
Citation: | American Journal of Psychiatry, 2014; 171(12):1297-1309 |
Publisher: | American Psychiatric Publishing |
Issue Date: | 2014 |
ISSN: | 0002-953X 1535-7228 |
Statement of Responsibility: | Ma-Li Wong, Chuanhui Dong, Deborah L. Flores, Monika Ehrhart-Bornstein, Stefan Bornstein, Mauricio Arcos-Burgos, Julio Licinio |
Abstract: | OBJECTIVE: The authors compared the effectiveness of fluoxetine and desipramine treatment in a prospective double-blind pharmacogenetics study in first-generation Mexican Americans and examined the role of whole-exome functional gene variations in the patients' antidepressant response. METHOD: A total of 232 Mexican Americans who met DSM-IV criteria for major depressive disorder were randomly assigned to receive 8 weeks of double-blind treatment with desipramine (50-200 mg/day) or fluoxetine (10-40 mg/day) after a 1-week placebo lead-in period. Outcome measures included the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale, and the Beck Depression Inventory. At week 8, whole-exome genotyping data were obtained for 36 participants who remitted and 29 who did not respond to treatment. RESULTS: Compared with desipramine treatment, fluoxetine treatment was associated with a greater reduction in HAM-D score, higher response and remission rates, shorter time to response and remission, and lower incidences of anticholinergic and cardiovascular side effects. Pharmacogenetics analysis showed that exm-rs1321744 achieved exome-wide significance for treatment remission. This variant is located in a brain methylated DNA immunoprecipitation sequencing site, which suggests that it may be involved in epigenetic regulation of neuronal gene expression. This and two other common gene variants provided a highly accurate cross-validated predictive model for treatment remission of major depression (receiver operating characteristic integral=0.95). CONCLUSIONS: Compared with desipramine, fluoxetine treatment showed a more rapid reduction of HAM-D score and a lower incidence of side effects in a population comprising primarily first-generation Mexican Americans with major depression. This study's pharmacogenetics approach strongly implicates the role of functional variants in antidepressant treatment response. |
Keywords: | Humans |
Rights: | Copyright © American Psychiatric Association. All rights reserved. |
DOI: | 10.1176/appi.ajp.2014.12091165 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1051931 |
Published version: | http://dx.doi.org/10.1176/appi.ajp.2014.12091165 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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