Department of Psychiatry, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
South Texas Diabetes and Obesity Institute and Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Brain Behav Immun. 2019 Aug;80:292-299. doi: 10.1016/j.bbi.2019.04.004. Epub 2019 Apr 3.
Suicide is major public health concern. It is imperative to find robust biomarkers so that at-risk individuals can be identified in a timely and reliable manner. Previous work suggests mechanistic links between increased cytokines and risk for suicide, but questions remain regarding the etiology of this association, as well as the roles of sex and BMI.
Analyses were conducted using a randomly-ascertained extended-pedigree sample of 1882 Mexican-American individuals (60% female, mean age = 42.04, range = 18-97). Genetic correlations were calculated using a variance components approach between the cytokines TNF-α, IL-6 and IL-8, and Lifetime Suicide Attempt and Current Suicidal Ideation. The potentially confounding effects of sex and BMI were considered.
159 individuals endorse a Lifetime Suicide Attempt. IL-8 and IL-6 shared significant genetic overlap with risk for suicide attempt (ρ = 0.49, p = 7.67 × 10; ρ = 0.53, p = 0.01), but for IL-6 this was attenuated when BMI was included as a covariate (ρ = 0.37, se = 0.23, p = 0.12). Suicide attempts were significantly more common in females (p = 0.01) and the genetic overlap between IL-8 and risk for suicide attempt was significant in females (ρ = 0.56, p = 0.01), but not in males (ρ = 0.44, p = 0.30).
These results demonstrate that: IL-8 shares genetic influences with risk for suicide attempt; females drove this effect; and BMI should be considered when assessing the association between IL-6 and suicide. This finding represents a significant advancement in knowledge by demonstrating that cytokine alterations are not simply a secondary manifestation of suicidal behavior, but rather, the pathophysiology of suicide attempts is, at least partly, underpinned by the same biological mechanisms responsible for regulating inflammatory response.
自杀是一个严重的公共卫生问题。迫切需要找到强有力的生物标志物，以便能够及时、可靠地识别出高危个体。先前的研究表明，细胞因子的增加与自杀风险之间存在机制联系，但关于这种关联的病因以及性别和 BMI 的作用仍存在疑问。
使用随机确定的 1882 名墨西哥裔美国人的扩展家系样本进行分析（60%为女性，平均年龄为 42.04 岁，范围为 18-97 岁）。使用方差成分法计算细胞因子 TNF-α、IL-6 和 IL-8 与终生自杀尝试和当前自杀意念之间的遗传相关性。考虑了性别和 BMI 的潜在混杂效应。
有 159 人有过终生自杀尝试。IL-8 和 IL-6 与自杀尝试风险有显著的遗传重叠（ρ=0.49，p=7.67×10；ρ=0.53，p=0.01），但当将 BMI 作为协变量包含在内时，IL-6 的这种重叠就减弱了（ρ=0.37，se=0.23，p=0.12）。女性自杀尝试的比例明显更高（p=0.01），IL-8 与自杀尝试风险之间的遗传重叠在女性中显著（ρ=0.56，p=0.01），但在男性中不显著（ρ=0.44，p=0.30）。
这些结果表明：IL-8 与自杀尝试风险有遗传影响；女性驱动了这种效应；在评估 IL-6 与自杀之间的关联时，应考虑 BMI。这一发现是一个重大的知识进步，它表明细胞因子的改变不仅仅是自杀行为的继发表现，而是自杀尝试的病理生理学至少部分是由负责调节炎症反应的相同生物学机制所支撑的。
