Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study
Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study
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DOI：
10.1001/archpsyc.64.6.689
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Smoller, Jordan W.
中科院分区：
文献类型：
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作者：
Perlis, Roy H.;Purcell, Shaun;Smoller, Jordan W.
内容：一小部分抑郁症患者在短期抗抑郁药治疗期间表现出新的或恶化的自杀想法或行为。由于环磷酸腺苷反应元件结合（CREB）蛋白参与了抗抑郁机制和自杀，CREB 1基因代表了一个可能影响治疗后出现的自杀倾向风险的基因。目的：研究跨越CREB 1的多态性与新的或恶化的自杀倾向的关系，CREB 1以前与重度抑郁症男性的愤怒表达有关。巢式病例对照研究来自缓解抑郁症的序贯替代治疗（星星 *D）研究，一项多中心、前瞻性、开放性、12周有效性试验，从2001年7月1日至2006年9月30日。在研究开始时，有DNA可供使用且未报告自杀意念的非精神病性重度抑郁症患者随后接受氢溴酸西酞普兰治疗长达12周。紧急自杀意念，定义为2分或更高的任何postbaseline访问的参与者的基线评分为0或1的16项快速清单的抑郁症状，临床医生评定suicide item.Results：1447名参与者，124（8.6%）随后报告自杀至少1次访问，这些人与其余1324名参与者进行了比较。在检测的5个单核苷酸多态性（SNP）中，没有一个与治疗后出现的自杀倾向显著相关。然而，2个SNPs揭示了基因与性别的相互作用与自杀倾向。在539名男子中，这2个SNP和2的5个SNP单倍型，显着相关的新发suicidality.Conclusions：多态性跨越CREB1与治疗后出现的自杀男性抑郁症，延长观察与男性愤怒的表达在先前的独立队列。如果重复，这一发现将表明，药物遗传学测试可以促进识别在短期抗抑郁药治疗中风险更大的一小部分个体。
Context: A small subset of patients with depression exhibit new or worsening suicidal thoughts or behavior during short-term treatment with antidepressants. Because cyclic adenosine monophosphate response element binding (CREB) protein has been implicated in both antidepressant mechanisms and suicide, the CREB1 gene represents a gene that possibly influences the risk for treatment-emergent suicidality.Objective: To examine polymorphisms that span CREB1, which was previously associated with anger expression in men with major depressive disorder, for association with new or worsening suicidality.Design: Nested case-control study derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter, prospective, open, 12-week effectiveness trial from July 1, 2001, to September 30, 2006.Setting: Outpatient primary care and psychiatric clinics.Patients: Individuals with nonpsychotic major depressive disorder for whom DNA was available and who did not report suicidal ideation at study entry were subsequently treated with citalopram hydrobromide for up to 12 weeks.Main Outcome Measure: Emergent suicidal ideation, defined as a score of 2 or higher on any postbase-line visit for participants whose baseline score was 0 or 1 on the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated suicide item.Results: Of 1447 participants, 124 (8.6%) subsequently reported suicidality on at least 1 visit; these individuals were compared with the remaining 1324 participants. Of 5 single nucleotide polymorphisms (SNPs) examined, none were significantly associated with treatment-emergent suicidality overall. However, 2 SNPs revealed a gene-by-sex interaction with suicidality. Among the 539 men, these 2 SNPs and 2 of the 5 SNP haplotypes; were significantly associated with new-onset suicidality.Conclusions: Polymorphisms that span CREB1 were associated with treatment-emergent suicidality among men with depression, extending an observation of association with male anger expression in a prior independent cohort. If replicated, this finding would suggest that pharmacogenetic testing could facilitate the identification of the small subset of individuals at greater risk during short-term antidepressant treatment.