Genetic markers of suicidal ideation emerging during citalopram treatment of major depression.
OBJECTIVE
Suicidal ideation is an uncommon symptom than can emerge during antidepressant treatment. The biological basis of treatment-emergent suicidal ideation is unknown. Genetic markers may shed light on the causes of treatment-emergent suicidal ideation and help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, or specialty care.


METHODS
A clinically representative cohort of outpatients with major depressive disorder who 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 1,915 participants were genotyped for 768 single-nucleotide polymorphisms in 68 candidate genes. Allele and genotype frequencies were compared between the 120 participants who developed treatment-emergent suicidal ideation and those who did not.


RESULTS
Two markers were significantly associated with treatment-emergent suicidal ideation in this sample (marker rs4825476, p=0.0000784, odds ratio=1.94; permutation p=0.01; marker rs2518224, p=0.0000243, odds ratio=8.23; permutation p=0.003). These markers reside within the genes GRIA3 and GRIK2, respectively, both of which encode ionotropic glutamate receptors.


CONCLUSIONS
Markers within GRIK2 and GRIA3 were associated with treatment-emergent suicidal ideation during citalopram therapy. If replicated, these findings may shed light on the biological basis of this potentially dangerous adverse event and help identify patients at increased risk.
Laje
Gonzalo
G
Genetic Basis of Mood and Anxiety Disorders, NIMH, 35 Convent Dr., Rm. 1A207, Bethesda, MD 20892-3719, USA. gonzalo.laje@nih.gov
Paddock
Silvia
S
Manji
Husseini
H
Rush
A John
AJ
Wilson
Alexander F
AF
Charney
Dennis
D
McMahon
Francis J
FJ
D000328:Adult; D000553:Ambulatory Care; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017470:Receptors, Glutamate / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D013405:Suicide / Q000523:psychology*; D016896:Treatment Outcome; D014481:United States
D015283:Citalopram; D005819:Genetic Markers; D017470:Receptors, Glutamate; D017367:Selective Serotonin Reuptake Inhibitors