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).

抗抑郁药的处方是预防自杀和自杀行为最常用的策略之一。然而，一些患者在抗抑郁药治疗开始时出现自杀意念，这种现象被称为治疗出现的自杀意念 (TESI)。很少有研究探讨 TESI 药物基因组学。由于下丘脑-垂体-肾上腺 (HPA) 轴可能与自杀行为有关，我们评估了与 HPA 轴相关的NR3C1 ( n  = 7 SNP)、FKBP5 ( n  = 5 ) 中 TESI 与单核苷酸多态性 (SNP) 之间的关系SNP）、AVPR1B（n  = 1 个 SNP）、CRHR1（n  = 1 个 SNP）和SKA2( n  = 1 SNP) 基因，在 3566 名接受抗抑郁治疗的成年抑郁症门诊患者样本中。法国各地的全科医生和精神科医生在首次开具噻奈普汀（一种显示 mu 激动作用的抗抑郁分子）后对参与者进行了 6 周的随访。在基线和治疗的第 2、4 和 6 周，使用 Montgomery-Åsberg 抑郁量表的第 10 项（专门用于自杀意念的项目）评估自杀意念。在信息丰富的样本中，112 名患者报告了 TESI，384 名没有。TESI 与FKBP5 中SNP rs6902321 的 TT 基因型（OR = 1.76，95 % CI = [1.07；2.90]；p值 = 0.03）和 SNP rs7208505 中的 GG/AG 基因型显着相关SKA2（OR = 1.85，95 % CI = [1.03;3.33]；p值 = 0.04）。在多次测试校正后，这些关联不显着。尽管如此，我们的结果表明 HPA 轴元素可能参与治疗出现的自杀意念 (TESI)。