Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients.
Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients.
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DOI：
10.1097/fpc.0b013e32832e4bcd
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发表时间：
2009-09
影响因子：
2.6
通讯作者：
McMahon FJ
中科院分区：
文献类型：
--
作者：
Laje G;Allen AS;Akula N;Manji H;John Rush A;McMahon FJ
自杀意念是一种不常见但令人担忧的症状，在抗抑郁药治疗期间可能会出现。我们先前已经描述了治疗后出现的自杀意念（TESI）与编码谷氨酸受体GRIK 2和GRIA 3的基因中的标记物之间的关联。目前的全基因组关联研究旨在确定与TESI相关的其他遗传标记，这些标记可能有助于识别高风险个体，这些个体可能受益于更密切的监测，替代治疗和/或专业护理。在缓解抑郁症的序贯治疗替代方案（星星 *D）试验中招募的具有临床代表性的非精神病性重度抑郁症门诊患者队列，根据标准方案接受西酞普兰治疗长达14周。来自90名患有TESI的白色参与者和性别和种族匹配的同等数量的否认任何自杀想法的治疗参与者的DNA样本在Illumina的Human-1 BeadChip上进行了109，365个单核苷酸多态性的基因分型。在该样本中，发现一个标记物与TESI相关，实验范围内调整的p<0.05水平（标记物rs 11628713，等位基因p= 6.2 × 10-7，OR = 4.7，排列p=0.01）。第二个标志物在实验范围内调整的p=0.06水平上相关（rs 10903034，等位基因p = 3.02× 10-6，OR = 2.7，排列p=0.06）。这些标记分别位于基因PAPLN和IL 28 RA内。PAPLN编码乳头蛋白，一种原聚糖样硫酸化糖蛋白。IL 28 RA编码白细胞介素受体。结合我们之前的报告，这些发现可能揭示了TESI的生物学基础，并可能有助于识别这种潜在严重不良事件风险增加的患者。
Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have previously described association between treatment emergent suicidal ideation (TESI) and markers in genes encoding the glutamate receptors GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high-risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. A clinically-representative cohort of outpatients with non-psychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 white participants who developed TESI and a gender and race matched equal number of treated participants who denied any suicidal ideas were genotyped with 109,365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. One marker was found to be associated with TESI in this sample at the experiment-wide adjusted p<0.05 level (marker rs11628713, allelic p= 6.2 × 10-7, OR = 4.7, permutation p=0.01). A second marker was associated at the experiment-wide adjusted p=0.06 level (rs10903034, allelic p = 3.02× 10-6, OR = 2.7, permutation p=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. Together with our previous report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.