DNA Methylation and Inflammatory Signatures Associated with Suicide Risk and Treatment in US Veterans

 描述(由申请人提供)： 自杀是美国退伍军人的主要死亡原因。因此，了解自杀风险的病因学基础对我们的退伍军人来说是极其重要的。压力是自杀风险的关键因素。特别是对于退伍军人来说，在战斗、服兵役或部署后暴露于创伤性环境事件与重新适应平民生活相关的压力情况是增加自杀风险的关键因素。这些压力源 可影响自杀行为的素质，并可作为自杀行为的诱因或诱因。自杀风险因素的生物标记或稳定的行为特征可能以一种复杂的方式相互作用，这可能受益于可以检查基因与环境相互作用的方法。表观遗传学是连接环境和遗传的桥梁，通过调节环境因素，如应激，改变与自杀相关的基因表达的调节。我们将使用基因组规模的方法研究在JJP VAMC接受精神治疗的退伍军人中与自杀风险相关的DNA甲基化模式。此外，通过后续研究，我们将评估DNA甲基化模式在治疗后如何改变。这样的纵向研究是史无前例的，为确定自杀风险和治疗反应的生物标记物提供了机会。此外，在这些研究中，还将研究炎症反应在压力素质和自杀风险中的作用。结合自杀风险和治疗的表观遗传和炎症标记物，将确定我们可以在临床环境中使用的客观措施，以识别有自杀风险的退伍军人，并确定治疗过程和反应的疗效。

 DESCRIPTION (provided by applicant): Suicide is a leading cause of death among U.S. Veterans. Therefore, understanding the etiological basis for the risk of suicide is of dire importance to our Veteran population. Stress i a crucial factor in risk of suicide. Specifically for Veterans, exposure to traumatic environmental events during combat, military service, or post- deployment stressful situations related to readjustment to civilian life are key contributors to the increase risk of suicide. These stressors can affect the diathesis for suicidal acts and can serve as triggers or precipitants of suicidal acts. Biological markers or stable behavioral traits for suicide risk factors likely interact in a complex manner that might benefit from approaches that can examine gene by environment interactions. Epigenetics is the bridge, connecting environment with genetics, by mediating the influence of environmental factors such as stress in altered regulation of gene expression related to suicide. We will investigate DNA methylation patterns associated with suicide risk in Veterans undergoing psychiatric treatment at the JJP VAMC using a genome- scale approach. Additionally, through subsequent follow-up studies, we will assess how DNA methylation patterns are altered following treatment. Such a longitudinal study is unprecedented and provides an opportunity to identify biological markers of suicide risk and treatment response. Moreover, the role of the inflammatory response in the stress diathesis in suicide risk will also be investigated in these studies. Together the epigenetic and inflammatory markers of suicide risk and treatment will identify objective measures that we can use in clinical settings to identif Veterans at risk of suicide and to determine the efficacy of treatment course and response.