Department of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden.
Department of Clinical Neuroscience/Psychology, Karolinska Institute, Stockholm, Sweden.
Transl Psychiatry. 2022 Jun 2;12(1):224. doi: 10.1038/s41398-022-01998-8.
Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.
自杀企图（SA）与非自杀性死亡率过高有关，部分原因是过早的细胞衰老。先前已经证明，生物年龄的表观遗传年龄（EA）估计值可以强烈预测生理失调和死亡风险。在此，我们研究是否具有高致死意图的暴力 SA 是否可以预测基于表观遗传学的生物老化估计值。使用全血中的 Illumina Infinium Methylation EPIC BeadChip 测量了全基因组甲基化模式。根据 SA 方法（暴力或非暴力）和/或致死意图（高/低），将 88 名自杀未遂者分为两组，基于以后自杀的假定风险。内在和外在 EA 加速的估计值，一个优化用于预测生理失调的标记物（DNAmPhenoAge/AgeAccelPheno）和一个优化用于预测寿命的标记物（DNAmGrimAge/AgeAccelGrim），通过单变量和多变量分析，研究了它们与 SA 严重程度的关系。该研究有足够的能力来检测与 SA 严重程度相关的 AgeAccelGrim 差异 2.2 年。在所有样本中，基线 DNAmGrimAge 平均比实际年龄高 7.3 岁，相对于实际年龄平均增加了 24.6%。没有单个 EA 加速标记物可以通过自杀风险组来区分（p>0.1）。因此，SA 本身而不是 SA 的严重程度与 EA 有关，这意味着 SA 中的非自杀性死亡率过高与自杀风险无关。旨在减少 SA 后过度死亡率的预防保健工作可能受益于同等强大的作用，无论行为本身所固有的严重程度如何，都可以识别躯体共病。
