Genetic markers of suicidal ideation emerging during citalopram treatment of major depression.

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Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ

Genetic markers of suicidal ideation emerging during citalopram treatment of major depression.

Am J Psychiatry. 2007 Oct;164(10):1530-8.

PubMed ID

17898344 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Pharmaco-genomics

Drug	Interacting Gene/Enzyme	Allele name	Genotypes	Defining change(s)	Type(s)	Description	Details
Citalopram	Glutamate receptor ionotropic, kainate 2 Gene symbol: GRIK2 UniProt: Q13002	---	(C;C)	C Allele, homozygote (rs2518224)	ADR Directly Studied	Patients with this genotype have increased frequency of suicidal ideation with citalopram	Details
Citalopram	Glutamate receptor 3 Gene symbol: GRIA3 UniProt: P42263	---	(G;G) / (G;A)	G allele (rs4825476)	ADR Directly Studied	Patients with this genotype have increased frequency of suicidal ideation with citalopram	Details