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

Gonzalo Laje · Andrew S. Allen · Nirmala Akula · Husseini K. Manji · Augustus John Rush · Francis J. McMahon

112 citations0/0 files storedPharmacogenetics and Genomics

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Suicide and Self-Harm Studies Genetic Associations and Epidemiology Treatment of Major Depression

Abstract

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 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. 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.

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References

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2011A pilot genome wide association and gene expression array study of suicide with and without major depression 2020Genetic aetiology of self-harm ideation and behaviour 2022Risk of Suicidal Behaviors and Antidepressant Exposure Among Children and Adolescents: A Meta-Analysis of Observational Studies

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