Lanctôt Krista L, Rapoport Mark J, Chan Florance, Rajaram Ryan D, Strauss John, Sicard Tricia, McCullagh Scott, Feinstein Anthony, Kiss Alex, Kennedy James L, Bassett Anne S, Herrmann Nathan
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Brain Inj. 2010;24(7-8):959-69. doi: 10.3109/02699051003789229.
To determine which serotonergic system-related single nucleotide polymorphisms (SNPs) predicted variation in treatment response to citalopram in depression following a traumatic brain injury (TBI).
Ninety (50 M/40 F, aged 39.9, SD = 18.0 years) post-TBI patients with a major depressive episode (MDE) were recruited into a 6-week open-label study of citalopram (20 mg/day). Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025).
MTHFR and BDNF SNPs predicted greater treatment response (R(2)= 0.098, F = 4.65, p = 0.013). The 5HTTLPR predicted greater occurrence of adverse events (R(2)= 0.069, F = 5.72, p = 0.020).
Results suggest that polymorphisms in genes related to the serotonergic system may help predict short-term response to citalopram and tolerability to the medication in patients with MDE following a TBI.
确定哪些与血清素能系统相关的单核苷酸多态性（SNP）可预测创伤性脑损伤（TBI）后抑郁症患者对西酞普兰治疗反应的差异。
招募了90名（50名男性/40名女性，年龄39.9岁，标准差 = 18.0岁）患有重度抑郁发作（MDE）的TBI后患者，进行为期6周的西酞普兰（20毫克/天）开放标签研究。检测了与血清素能系统相关基因中的6个功能性SNP：血清素转运体（5HTTLPR，包括rs25531）、5HT1A C-(1019)G和5HT2A T-(102)C、亚甲基四氢叶酸还原酶（MTHFR）C-(677)T、脑源性神经营养因子（BDNF）val66met和色氨酸羟化酶-2（TPH2）G-(703)T。使用这6个SNP作为自变量进行回归分析：模型1以反应（汉密尔顿抑郁量表（HAMD）从基线到终点的变化百分比）作为因变量，模型2以不良事件指数作为因变量（经Bonferroni校正的p值 < 0.025）。
MTHFR和BDNF的SNP预测了更好的治疗反应（R(2)= 0.098，F = 4.65，p = 0.013）。5HTTLPR预测了更高的不良事件发生率（R(2)= 0.069，F = 5.72，p = 0.020）。
结果表明，与血清素能系统相关的基因多态性可能有助于预测TBI后MDE患者对西酞普兰的短期反应和药物耐受性。
