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

Ma Li Wong, Chuanhui Dong, Deborah L. Flores, Monika Ehrhart-Bornstein, Stefan Bornstein, Mauricio Arcos-Burgos, Julio Licinio

Research output: Contribution to journalArticle

24 Citations (Scopus)

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. Outcomemeasures 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: Comparedwith 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 ofmajor depression (receiver operating characteristic integral=0.95).

Conclusions: Compared with desipramine, fluoxetine treatment showed amore rapid reduction of HAM-Dscore 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.

Original languageEnglish
Pages (from-to)1297-1309
Number of pages13
JournalAmerican Journal of Psychiatry
Volume171
Issue number12
DOIs
StatePublished - Jan 1 2014

Fingerprint

Methylation
Antidepressive Agents
Genome
Brain
Desipramine
Fluoxetine
Exome
Depression
Therapeutics
Pharmacogenomic Testing
Mexican Americans
Antidepressants
Pharmacogenetics
Incidence
Major Depressive Disorder
Cholinergic Antagonists
Gene Expression Regulation
DNA Sequence Analysis
Immunoprecipitation
Double-Blind Method

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

Cite this

Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans. / Wong, Ma Li; Dong, Chuanhui; Flores, Deborah L.; Ehrhart-Bornstein, Monika; Bornstein, Stefan; Arcos-Burgos, Mauricio; Licinio, Julio.

In: American Journal of Psychiatry, Vol. 171, No. 12, 01.01.2014, p. 1297-1309.

Research output: Contribution to journalArticle

Wong, Ma Li ; Dong, Chuanhui ; Flores, Deborah L. ; Ehrhart-Bornstein, Monika ; Bornstein, Stefan ; Arcos-Burgos, Mauricio ; Licinio, Julio. / Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans. In: American Journal of Psychiatry. 2014 ; Vol. 171, No. 12. pp. 1297-1309.
@article{50364f40acc14354807247a3c22b8432,
title = "Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans",
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. Outcomemeasures 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: Comparedwith 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 ofmajor depression (receiver operating characteristic integral=0.95).Conclusions: Compared with desipramine, fluoxetine treatment showed amore rapid reduction of HAM-Dscore 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 = "Wong, {Ma Li} and Chuanhui Dong and Flores, {Deborah L.} and Monika Ehrhart-Bornstein and Stefan Bornstein and Mauricio Arcos-Burgos and Julio Licinio",
year = "2014",
month = "1",
day = "1",
doi = "10.1176/appi.ajp.2014.12091165",
language = "English",
volume = "171",
pages = "1297--1309",
journal = "American Journal of Psychiatry",
issn = "0002-953X",
publisher = "American Psychiatric Association",
number = "12",

}

TY - JOUR

T1 - Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans

AU - Wong, Ma Li

AU - Dong, Chuanhui

AU - Flores, Deborah L.

AU - Ehrhart-Bornstein, Monika

AU - Bornstein, Stefan

AU - Arcos-Burgos, Mauricio

AU - Licinio, Julio

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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. Outcomemeasures 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: Comparedwith 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 ofmajor depression (receiver operating characteristic integral=0.95).Conclusions: Compared with desipramine, fluoxetine treatment showed amore rapid reduction of HAM-Dscore 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.

AB - 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. Outcomemeasures 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: Comparedwith 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 ofmajor depression (receiver operating characteristic integral=0.95).Conclusions: Compared with desipramine, fluoxetine treatment showed amore rapid reduction of HAM-Dscore 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.

UR - http://www.scopus.com/inward/record.url?scp=84914106962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84914106962&partnerID=8YFLogxK

U2 - 10.1176/appi.ajp.2014.12091165

DO - 10.1176/appi.ajp.2014.12091165

M3 - Article

VL - 171

SP - 1297

EP - 1309

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 12

ER -