Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans
Language: 
English
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.

Author(s): 
Wong, Ma-Li
Dong, Chuanhui
Flores, Deborah L.
Ehrhart-Bornstein, Monika
Bornstein, Stefan
Arcos-Burgos, Mauricio
Licinio, Julio
Item Type: 
Journal Article
Publication Title: 
The American Journal of Psychiatry
Journal Abbreviation: 
Am J Psychiatry
Publication Date: 
12/1/2014
Publication Year: 
2014
Pages: 
1297-1309
Volume: 
171
Issue: 
12
ISSN: 
1535-7228
DOI: 
10.1176/appi.ajp.2014.12091165
Library Catalog: 
PubMed
Extra: 
PMID: 25220861

Turabian/Chicago Citation

Ma-Li Wong, Chuanhui Dong, Deborah L. Flores, Monika Ehrhart-Bornstein, Stefan Bornstein, Mauricio Arcos-Burgos and Julio Licinio. 12/1/2014. "Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans." The American Journal of Psychiatry 171: 12: 1297-1309. 10.1176/appi.ajp.2014.12091165.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1176/appi.ajp.2014.12091165 | issn = 1535-7228 | volume = 171 | pages = 1297-1309 | last = Wong | first = Ma-Li | coauthors = Dong, Chuanhui, Flores, Deborah L., Ehrhart-Bornstein, Monika, Bornstein, Stefan, Arcos-Burgos, Mauricio, Licinio, Julio | title = Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans | journal = The American Journal of Psychiatry | date = 12/1/2014 | pmid = | pmc = }} </ref>