自杀死亡的时间效应:经验证据和可能的分子相关性

R Bhagar, H Le-Niculescu, K Roseberry, K Kosary, C Daly, A Ballew, M Yard, G E Sandusky, A B Niculescu
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摘要

长期以来,流行文化和医学知识一直认为满月和精神疾病恶化之间存在联系。我们想对满月前后自杀人数增加的假设进行实证分析。我们分析了马里恩县验尸官办公室(n = 776),并显示自杀死亡人数在满月的一周内显著增加(p = 0.037),与老年人(年龄 ≥ 55)显示出更强的效果(p = 0.019)。我们还在数据集中检查了一天中的哪个时间(下午3-4点,p = 0.035),以及一年中的哪个月(9月,p = 0.09)显示自杀死亡人数最多。我们对一部分受试者(n = 45),这使我们能够研究可能的分子机制。我们测试了一份关于自杀的顶级血液生物标志物列表(n = 154),以评估其中哪些是预测性的。与满月、一天中的高峰时间和一年中的高峰月之外相比,分别预测自杀死亡的自杀生物标志物似乎富含生物钟基因。满月是AHCYL2、ACSM3、AK2和RBM3。高峰时段为GSK3B、AK2和PRKCB。高峰月份为TBL1XR1和PRKCI。这些基因中有一半被锂和丙戊酸钠以与自杀相反的方向调节表达,所有这些基因都被抑郁症和酒精以与自杀相同的方向调节。这些数据表明,自杀有时间效应,可能是由生物钟介导的,表明环境光照(时间和强度)的变化是减少自杀的治疗目标,可以与精神药物和成瘾治疗预防干预相结合。
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Temporal effects on death by suicide: empirical evidence and possible molecular correlates.

Popular culture and medical lore have long postulated a connection between full moon and exacerbations of psychiatric disorders. We wanted to empirically analyze the hypothesis that suicides are increased during the period around full moons. We analyzed pre-COVID suicides from the Marion County Coroner's Office (n = 776), and show that deaths by suicide are significantly increased during the week of the full moon (p = 0.037), with older individuals (age ≥ 55) showing a stronger effect (p = 0.019). We also examined in our dataset which hour of the day (3-4 pm, p = 0.035), and which month of the year (September, p = 0.09) show the most deaths by suicide. We had blood samples on a subset of the subjects (n = 45), which enabled us to look at possible molecular mechanisms. We tested a list of top blood biomarkers for suicidality (n = 154) from previous studies of ours 7, to assess which of them are predictive. The biomarkers for suicidality that are predictive of death by suicide during full moon, peak hour of day, and peak month of year, respectively, compared to outside of those periods, appear to be enriched in circadian clock genes. For full moon it is AHCYL2, ACSM3, AK2, and RBM3. For peak hour it is GSK3B, AK2, and PRKCB. For peak month it is TBL1XR1 and PRKCI. Half of these genes are modulated in expression by lithium and by valproate in opposite direction to suicidality, and all of them are modulated by depression and alcohol in the same direction as suicidality. These data suggest that there are temporal effects on suicidality, possibly mediated by biological clocks, pointing to changes in ambient light (timing and intensity) as a therapeutically addressable target to decrease suicidality, that can be coupled with psychiatric pharmacological and addiction treatment preventive interventions.

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