Polymorphisms of stress pathway genes and emergence of suicidal ideation at antidepressant treatment onset.
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ABSTRACT: The prescription of antidepressant drugs is one of the most frequently used strategies to prevent suicide and suicidal behavior. However, some patients develop suicidal ideation at antidepressant treatment onset, a phenomenon known as treatment-emergent suicidal ideation (TESI). Few studies have explored TESI pharmacogenomics. As the Hypothalamic-Pituitary-Adrenal (HPA) axis might be implicated in suicidal behavior, we assessed the relationship between TESI and single nucleotide polymorphisms (SNPs) in the HPA axis-implicated NR3C1 (n?=?7 SNPs), FKBP5 (n?=?5 SNPs), AVPR1B (n?=?1 SNPs), CRHR1 (n?=?1 SNPs), and SKA2 (n?=?1 SNPs) genes, in a sample of 3566 adult outpatients with depression for whom an antidepressant treatment was introduced. General practitioners and psychiatrists throughout France followed participants for 6 weeks after the initial prescription of tianeptine, an antidepressant molecule showing mu agonism. Suicidal ideation was assessed with item 10 of the Montgomery-Åsberg Depression Rating Scale (item dedicated to suicidal ideation) at baseline, and at week 2, 4, and 6 of treatment. Within the informative sample, 112 patients reported TESI and 384 did not. TESI was significantly associated with the TT genotype of the SNP rs6902321 in FKBP5 (OR?=?1.76, 95% CI?=?[1.07; 2.90]; p-value?=?0.03) and the GG/AG genotype of the SNP rs7208505 in SKA2 (OR?=?1.85, 95% CI?=?[1.03;3.33]; p-value?=?0.04). These associations were not significant after multiple test correction. Nevertheless, our results suggest a possible involvement of HPA axis elements in treatment-emergent suicidal ideation (TESI).
SUBMITTER: Nobile B
PROVIDER: S-EPMC7502493 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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