Citation

Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney DS, McMahon FJ. Am. J. Psychiatry 2007; 164(10): 1530-1538.

Affiliation

Genetic Basis of Mood and Anxiety Disorders, NIMH, 35 Convent Dr., Rm. 1A207, Bethesda, MD 20892-3719, USA. gonzalo.laje@nih.gov

Comment In:

Am J Psychiatry. 2008 Mar;165(3):395; author reply 395-6

Copyright

(Copyright © 2007, American Psychiatric Association)

DOI

10.1176/appi.ajp.2007.06122018

PMID

17898344

Abstract

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. METHOD: 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.

Language: en