The Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 2002 Holcombe Blvd., Research 151, Building 110, Suite 227, Houston, TX, 77030, USA.
Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, USA.
Eur Arch Psychiatry Clin Neurosci. 2020 Aug;270(5):633-642. doi: 10.1007/s00406-019-01009-w. Epub 2019 Mar 28.
Variants in three genes coding for components of the serotonergic system, the tryptophan hydroxylase 1 (TPH1) rs1799913, serotonin transporter (SLC6A4) 5-HTTLPR, and serotonin receptor 2A (HTR2A) rs6311, were evaluated for association with suicidal ideation (SI) and with recovery from SI in a psychiatric inpatient population. Five hundred and eighty-two adult inpatients, including 390 patients who had SI, collected from December 2012 to April 2016 were assessed. SI recovery, calculated as change in SI between the first two-week period after admission and weeks 5 and 6, was appraised for association with the three variants. In this preliminary study, both TPH1 and 5-HTTLPR genotypes were associated with recovery (TPH1: recessive model, increased recovery with AC genotype, P = 0.026; additive model, increased recovery with AC genotype, P = 0.037; 5-HTTLPR: recessive model, increased recovery with AC, P = 0.043). When patients with comorbid alcohol use disorder (AUD) were removed, given that TPH1 has been associated with alcoholism, the associations of those recovered from SI with TPH1 rs1799913 remained significant for the additive (increased recovery with AC, P = 0.045) and recessive (increased recovery with C-carriers, P = 0.008) models, and with 5-HTTLPR using the dominant model (increased recovery with S'S', P = 0.016). In females, an association of SI recovery with TPH1 rs1799913 was found using a recessive model (increased recovery with C-carriers, P = 0.031), with 5-HTTLPR using additive (increased recovery with L'S', P = 0.048) and recessive (increased recovery with S'S', P = 0.042) models. Additionally, an association of SI with TPH1 rs1799913 was found in females using both additive (increased risk in AC, P = 0.033) and recessive (increased risk in C-carriers, P = 0.043) models, and with 5-HTTLPR using a recessive model (increased risk in S'S', P = 0.030). This study provides evidence that variation in the TPH1 and serotonin transporter genes play key roles in moderating recovery from SI during treatment in an inpatient psychiatric clinic.
该研究评估了编码 5-羟色胺能系统成分的三个基因（色氨酸羟化酶 1（TPH1）rs1799913、血清素转运体（SLC6A4）5-HTTLPR 和 5-羟色胺受体 2A（HTR2A）rs6311）的变体与自杀意念（SI）和精神病住院患者人群中 SI 的恢复之间的关联。该研究纳入了 2012 年 12 月至 2016 年 4 月期间采集的 582 名成年住院患者，其中 390 名患者存在 SI。SI 恢复是指入院后前两周与第 5 周和第 6 周之间 SI 的变化，评估其与三种变体的关联。在这项初步研究中，TPH1 和 5-HTTLPR 基因型均与恢复相关（TPH1：隐性模型，AC 基因型恢复增加，P=0.026；加性模型，AC 基因型恢复增加，P=0.037；5-HTTLPR：隐性模型，AC 恢复增加，P=0.043）。当排除患有合并酒精使用障碍（AUD）的患者时，鉴于 TPH1 与酗酒有关，与 SI 恢复相关的 TPH1 rs1799913 与加性（AC 恢复增加，P=0.045）和隐性（C 携带者恢复增加，P=0.008）模型，以及 5-HTTLPR 使用显性模型（S'S'恢复增加，P=0.016）的关联仍然显著。在女性中，发现 SI 恢复与 TPH1 rs1799913 之间存在隐性模型的关联（C 携带者恢复增加，P=0.031），与 5-HTTLPR 采用加性（L'S'恢复增加，P=0.048）和隐性（S'S'恢复增加，P=0.042）模型。此外，还发现女性中 TPH1 rs1799913 与 SI 之间存在加性（AC 风险增加，P=0.033）和隐性（C 携带者风险增加，P=0.043）模型的关联，以及 5-HTTLPR 采用隐性模型（S'S'风险增加，P=0.030）的关联。这项研究提供了证据，表明 TPH1 和血清素转运体基因的变异在住院精神病诊所的治疗过程中对调节 SI 的恢复起着关键作用。
