Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
Eur Neuropsychopharmacol. 2012 Apr;22(4):259-66. doi: 10.1016/j.euroneuro.2011.08.007. Epub 2011 Sep 21.
Many association studies have reported associations between the catechol-O-methyltransferase (COMT) gene and psychiatric disorders including major depression (MDD). The COMT gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. In the present study, we further elucidate the impact of COMT in treatment response in MDD patients with suicide risk and/or a personal history of suicide attempts. Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for seven SNPs (rs4680, rs2075507, rs737865, rs6269, rs4633, rs4818 and rs165599) within the COMT gene. With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. In non-responders, we found significant single marker and haplotypic association with suicide risk, but not in responders. The same holds true for both remitters and non-remitters, and when testing for association with a personal history of suicide attempts and treatment response phenotypes. In conclusion, we found significant association of COMT SNPs with suicide risk in MDD patients not responding to antidepressant treatment. Larger well-defined cohorts will be required to dissect this further.
许多关联研究报告了儿茶酚-O-甲基转移酶（COMT）基因与包括重度抑郁症（MDD）在内的精神疾病之间的关联。COMT 基因还与自杀行为以及治疗反应相关，尽管结果存在冲突。在本研究中，我们进一步阐明了 COMT 在有自杀风险和/或有自杀尝试个人史的 MDD 患者治疗反应中的作用。在一项欧洲多中心难治性抑郁症研究中，共收集了 250 名 MDD 患者，并使用抗抑郁药以足够剂量治疗至少 4 周。使用 Mini 国际神经精神访谈（MINI）和汉密尔顿抑郁量表（HAM-D）评估自杀倾向。治疗反应定义为抗抑郁药以足够剂量治疗 4 周后 HAM-D≤17，缓解定义为 HAM-D≤7。对 COMT 基因内的 7 个 SNP（rs4680、rs2075507、rs737865、rs6269、rs4633、rs4818 和 rs165599）进行基因分型。关于自杀风险和自杀尝试个人史，在多重测试校正后，没有发现任何 SNP 与单个标记或单倍型关联。在无反应者中，我们发现与自杀风险存在显著的单标记和单倍型关联，但在反应者中没有。这同样适用于缓解者和非缓解者，以及当测试与自杀尝试个人史和治疗反应表型的关联时。总之，我们发现 COMT SNP 与未对抗抑郁治疗有反应的 MDD 患者的自杀风险存在显著关联。需要更大、定义更明确的队列来进一步剖析这一关联。
