Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients.
OBJECTIVE
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 109 365 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 = 6.2x10, 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 = 3.02x10, 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.


CONCLUSIONS
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.
Laje
Gonzalo
G
Genetic Basis of Mood and Anxiety Disorders Unit, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. gonzalo.laje@nih.gov
Allen
Andrew S
AS
Akula
Nirmala
N
Manji
Husseini
H
John Rush
A
A
McMahon
Francis J
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010045:Outpatients; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013405:Suicide / Q000523:psychology* / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
D015283:Citalopram; D005819:Genetic Markers; D017367:Selective Serotonin Reuptake Inhibitors