Perlis Roy H, Purcell Shaun, Fava Maurizio, Fagerness Jesen, Rush A John, Trivedi Madhukar H, Smoller Jordan W
Massachusetts General Hospital, Boston, MA 02114, USA.
Arch Gen Psychiatry. 2007 Jun;64(6):689-97. doi: 10.1001/archpsyc.64.6.689.
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.
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.
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.
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.
Emergent suicidal ideation, defined as a score of 2 or higher on any postbaseline visit for participants whose baseline score was 0 or 1 on the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated suicide item.
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.
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.
一小部分抑郁症患者在接受抗抑郁药物短期治疗期间会出现新的或恶化的自杀念头或行为。由于环磷酸腺苷反应元件结合（CREB）蛋白与抗抑郁机制和自杀行为均有关联，因此CREB1基因可能是一个影响治疗中出现自杀倾向风险的基因。
研究跨越CREB1的多态性与新出现的或恶化的自杀倾向之间的关联，此前已有研究表明CREB1与重度抑郁症男性的愤怒表达有关。
嵌套病例对照研究，源自缓解抑郁症的序贯治疗替代方案（STAR*D）研究，这是一项多中心、前瞻性、开放性的为期12周的疗效试验，时间从2001年7月1日至2006年9月30日。
门诊初级保健和精神科诊所。患者为患有非精神病性重度抑郁症且有可用DNA且在研究开始时未报告有自杀意念的个体，随后接受氢溴酸西酞普兰治疗长达12周。
新发自杀意念，定义为对于在16项抑郁症状快速自评量表-临床医生评定自杀项目上基线评分为0或1的参与者，在任何基线后访视中评分为2或更高。
在1447名参与者中，124名（8.6%）随后至少在一次访视中报告有自杀倾向；将这些个体与其余1324名参与者进行比较。在所检测的5个单核苷酸多态性（SNP）中，总体上没有一个与治疗中出现的自杀倾向显著相关。然而，有2个SNP显示出与自杀倾向存在基因-性别交互作用。在539名男性中，这2个SNP以及5个SNP单倍型中的2个与新发自杀倾向显著相关。
跨越CREB1的多态性与抑郁症男性治疗中出现的自杀倾向有关，这扩展了之前在一个独立队列中观察到的与男性愤怒表达的关联。如果该发现得到重复验证，这将表明药物遗传学检测有助于识别在短期抗抑郁治疗期间处于较高风险的一小部分个体。
