Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.
PSNREC, Univ Montpellier, INSERM, CHU de Montpellier, Montpellier, France.
Transl Psychiatry. 2020 Sep 20;10(1):320. doi: 10.1038/s41398-020-01003-0.
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).
抗抑郁药物的处方是预防自杀和自杀行为最常用的策略之一。然而，一些患者在开始抗抑郁治疗时会出现自杀意念，这种现象被称为治疗中出现的自杀意念（TESI）。很少有研究探讨 TESI 的药物基因组学。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 TESI 与 HPA 轴相关的 NR3C1（n=7 个 SNP）、FKBP5（n=5 个 SNP）、AVPR1B（n=1 个 SNP）、CRHR1（n=1 个 SNP）和 SKA2（n=1 个 SNP）基因中的单核苷酸多态性（SNP）之间的关系，该研究纳入了 3566 名接受抗抑郁药治疗的成年门诊抑郁症患者。法国各地的全科医生和精神科医生在初始开处方使用具有μ激动作用的抗抑郁药硫胺庚噻吨后，对患者进行了 6 周的随访。自杀意念使用蒙哥马利-阿斯伯格抑郁评定量表（专门用于自杀意念的项目 10）在基线、治疗第 2、4 和 6 周进行评估。在信息样本中，有 112 名患者报告出现 TESI，而 384 名患者没有。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 SKA2 中 SNP rs7208505 的 GG/AG 基因型（OR=1.85，95%CI=[1.03；3.33]；p 值=0.04）显著相关。在经过多次测试校正后，这些关联并不显著。然而，我们的结果表明，HPA 轴元素可能参与治疗中出现的自杀意念（TESI）。
