Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients

Gonzalo Laje, Andrew S. Allen, Nirmala Akula, Husseini Manji, A. John Rush, Francis J. McMahon

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P=6.2×10, odds ratio=4.7, permutation P=0.01). A second marker was associated at the experiment-wide adjusted P=0.06 level (rs10903034, allelic P=3.02×10, odds ratio=2.7, permutation P=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.

Original languageEnglish (US)
Pages (from-to)666-674
Number of pages9
JournalPharmacogenetics and Genomics
Volume19
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

Fingerprint

Suicidal Ideation
Citalopram
Genome-Wide Association Study
Outpatients
Therapeutics
Odds Ratio
Interleukin Receptors
Major Depressive Disorder
Glutamate Receptors
Genetic Markers
Antidepressive Agents
Genes
Single Nucleotide Polymorphism
Glycoproteins
Depression
DNA

Keywords

  • Antidepressant
  • Citalopram
  • D
  • Genome-wide
  • Major depression
  • Pharmacogenetics
  • Selective serotonin reuptake inhibitor
  • STAR
  • Treatment-emergent suicidal ideation

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients. / Laje, Gonzalo; Allen, Andrew S.; Akula, Nirmala; Manji, Husseini; John Rush, A.; McMahon, Francis J.

In: Pharmacogenetics and Genomics, Vol. 19, No. 9, 09.2009, p. 666-674.

Research output: Contribution to journalArticle

Laje, Gonzalo ; Allen, Andrew S. ; Akula, Nirmala ; Manji, Husseini ; John Rush, A. ; McMahon, Francis J. / Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients. In: Pharmacogenetics and Genomics. 2009 ; Vol. 19, No. 9. pp. 666-674.
@article{82f7364cd8a94a719d0f9c99e63d056d,
title = "Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients",
abstract = "OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P=6.2×10, odds ratio=4.7, permutation P=0.01). A second marker was associated at the experiment-wide adjusted P=0.06 level (rs10903034, allelic P=3.02×10, odds ratio=2.7, permutation P=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.",
keywords = "Antidepressant, Citalopram, D, Genome-wide, Major depression, Pharmacogenetics, Selective serotonin reuptake inhibitor, STAR, Treatment-emergent suicidal ideation",
author = "Gonzalo Laje and Allen, {Andrew S.} and Nirmala Akula and Husseini Manji and {John Rush}, A. and McMahon, {Francis J.}",
year = "2009",
month = "9",
doi = "10.1097/FPC.0b013e32832e4bcd",
language = "English (US)",
volume = "19",
pages = "666--674",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients

AU - Laje, Gonzalo

AU - Allen, Andrew S.

AU - Akula, Nirmala

AU - Manji, Husseini

AU - John Rush, A.

AU - McMahon, Francis J.

PY - 2009/9

Y1 - 2009/9

N2 - OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P=6.2×10, odds ratio=4.7, permutation P=0.01). A second marker was associated at the experiment-wide adjusted P=0.06 level (rs10903034, allelic P=3.02×10, odds ratio=2.7, permutation P=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.

AB - OBJECTIVES: Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. METHODS: A clinically representative cohort of outpatients with nonpsychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. RESULTS: One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs11628713, allelic P=6.2×10, odds ratio=4.7, permutation P=0.01). A second marker was associated at the experiment-wide adjusted P=0.06 level (rs10903034, allelic P=3.02×10, odds ratio=2.7, permutation P=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. CONCLUSION: Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.

KW - Antidepressant

KW - Citalopram

KW - D

KW - Genome-wide

KW - Major depression

KW - Pharmacogenetics

KW - Selective serotonin reuptake inhibitor

KW - STAR

KW - Treatment-emergent suicidal ideation

UR - http://www.scopus.com/inward/record.url?scp=70249083016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70249083016&partnerID=8YFLogxK

U2 - 10.1097/FPC.0b013e32832e4bcd

DO - 10.1097/FPC.0b013e32832e4bcd

M3 - Article

C2 - 19724244

AN - SCOPUS:70249083016

VL - 19

SP - 666

EP - 674

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 9

ER -