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

被引:87
作者
Laje, Gonzalo [1 ]
Allen, Andrew S. [3 ]
Akula, Nirmala [1 ]
Manji, Husseini [2 ]
Rush, A. John [4 ,5 ]
McMahon, Francis J. [1 ]
机构
[1] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[2] NIMH, Lab Mol Pathophysiol Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
[3] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA
[4] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA
[5] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA
关键词
antidepressant; citalopram; genome-wide; major depression; pharmacogenetics; selective serotonin reuptake inhibitor; STAR*D; treatment-emergent suicidal ideation; SEQUENCED TREATMENT ALTERNATIVES; STAR-ASTERISK-D; REPORT QIDS-SR; QUICK INVENTORY; RATING-SCALE; SYMPTOMATOLOGY; RATIONALE; CHILDREN; TRIAL;
D O I
10.1097/FPC.0b013e32832e4bcd
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
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 rs1 1628713, allelic P=6.2 x 10(-7), 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 x 10(-6), 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 Pharmacogenetics and Genomics 19:666-674 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:666 / 674
页数:9
相关论文
共 28 条
[1]
[Anonymous], SUIC TRENDS YOUTHS Y
[2]
Efficient computation of significance levels for multiple associations in large studies of correlated data, including genomewide association studies [J].
Dudbridge, F ;
Koeleman, BPC .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (03) :424-435
[3]
Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study [J].
Fava, M ;
Rush, AJ ;
Trivedi, MH ;
Nierenberg, AA ;
Thase, ME ;
Sackeim, HA ;
Quitkin, FM ;
Wisniewski, S ;
Lavori, PW ;
Rosenbaum, JF ;
Kupfer, DJ .
PSYCHIATRIC CLINICS OF NORTH AMERICA, 2003, 26 (02) :457-+
[4]
*FOOD DRUG ADM, 2006, SUIC CHILDR AD BEING
[5]
*FOOD DRUG ADM, 2006, ANT US CHILDR AD AD
[6]
Early evidence on the effects of regulators' suicidality warnings on SSRI prescriptions and suicide in children and adolescents [J].
Gibbons, Robert D. ;
Brown, C. Hendricks ;
Hur, Kwan ;
Marcus, Sue M. ;
Bhaurnik, Dulal K. ;
Erkens, Joibile A. ;
Herings, Ron M. C. ;
Mann, J. John .
AMERICAN JOURNAL OF PSYCHIATRY, 2007, 164 (09) :1356-1363
[7]
A RATING SCALE FOR DEPRESSION [J].
HAMILTON, M .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1960, 23 (01) :56-62
[8]
Hamilton M., 1967, Br J Soc Clin Psychol, V6, P278, DOI 10.1111/j.2044-8260.1967.tb00530.x
[9]
Current concepts - Assessment and treatment of suicidal patients [J].
Hirschfeld, RMA ;
Russell, JM .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 337 (13) :910-915
[10]
Hosmer D.W., 2000, Applied Logistic Regression, V2nd ed.