Vagal fluctuation as a predictor of current and future depression

描述(申请人提供)：抑郁症是所有精神疾病中最普遍的疾病之一，占所有精神疾病经济成本的20%以上。一个重要的公共卫生优先事项是确定既增加个人抑郁易感性又阻碍从这种疾病中恢复的因素。心脏迷走神经控制的异常可能使人易患抑郁症。更具体地说，心脏迷走神经控制的两个明显异常可能导致易损性：通常在静息状态下测量的低迷走神经水平(VL)和通常根据环境要求测量的低迷走神经波动(VF)。VL和VF被越来越多地理解为身心健康结果的独立预测因子。到目前为止，情绪障碍的研究几乎完全集中在VL上，关于其病因学和预后价值的结果很大程度上是不确定的。我们实验室的早期数据表明，抑郁症的特征是低VF，VF可能预测随后的临床意义上的抑郁症的病程。这个R21探索性研究项目的广泛目标是调查室性心动过速作为抑郁症的易感标记物。我们将使用一系列先前验证的实验室任务，在60名被诊断为当前单相抑郁的门诊患者、30名既往被诊断为单相抑郁的参与者以及30名健康的非精神病科参与者中引发室颤。VL和VF将通过从心电图得出的高频心脏周期变异性进行评估。参与者将被纵向跟踪，并在六个月后重新评估。该项目的具体目的是检查：(1)抑郁易感性是否与实验应激源期间和之后的室颤减少存在横向关联；以及(2)那些在实验应激源期间和之后保持动态室颤的抑郁个体是否更有可能在六个月后从他们的障碍中恢复过来。研究人员打算将这些R21数据用作一个更大的R01研究资助项目的基础，该项目将检查以下方面的VF：(A)MDD以外的精神障碍；(B)预测较长时期(~3年)的结果；(C)在受控治疗模式中预测结果；以及(D)VF修饰的潜在抗抑郁效果。从公共卫生的角度来看，抑郁症风险与低VF有关的假设令人兴奋，因为它表明，可以使用容易获得的、潜在的可操作的心率变异性测量来帮助早期评估抑郁症风险，或许还可以开发直接对迷走神经通路本身进行操作的干预措施。公共卫生相关性：一个重要的公共卫生优先事项是确定既增加个人抑郁易感性又阻碍从这种疾病中恢复的因素。心脏迷走神经控制的异常可能使人易患抑郁症。这个项目将检验这样一种假设，即抑郁风险与缺乏动态的心脏迷走神经控制有关，这一假设具有潜在的重要意义，因为它表明，可以使用容易获得的、潜在的可操作的心率变异性测量来帮助早期评估抑郁风险，或许还可以开发直接对迷走神经通路本身进行操作的干预措施。

DESCRIPTION (provided by applicant): Depression is among the most prevalent of all psychiatric disorders, accounting for over 20% of economic costs for all mental illness. An important public health priority is the identification of factors that both increase individuals' vulnerability to depression and hinder recovery from this disorder. Abnormalities in cardiac vagal control may confer vulnerability to depression. More specifically, two distinct abnormalities in cardiac vagal control may confer vulnerability: low vagal level (VL) usually measured in a resting state, and low vagal fluctuation (VF), usually measured in response to environmental demands. VL and VF are increasingly understood as independent predictors of physical and mental health outcomes. To date, mood disorders research has focused almost exclusively on VL, with results largely inconclusive as to its etiological and prognostic value. Early data from our laboratory suggests that depression is characterized by low VF and that VF may predict the subsequent course of clinically significant depression. The broad objective of this R21 exploratory research project is to investigate VF as a liability marker for depression. We will use a battery of previously-validated laboratory tasks to elicit VF in 60 outpatients diagnosed with current unipolar depression, 30 participants with a past diagnosis of unipolar depression, and 30 healthy non-psychiatric participants. VL and VF will be assessed via high-frequency heart period variability derived from the electrocardiogram. Participants will be followed longitudinally and reassessed at six months. The specific aims of this project are to examine: (1) whether depression vulnerability is associated cross-sectionally with reduced VF during and after experimental stressors; and (2) whether those depressed individuals who preserve dynamic VF during and after experimental stressors are more likely to recover from their disorder six months later. The investigators intend to use these R21 data as the foundation for a larger R01 research grant project that will examine VF with respect to: (a) psychiatric disorders other than MDD; (b) predicting outcome over longer periods (~3 years); (c) predicting outcome in a controlled treatment modality; and (d) potential antidepressant effects of VF modification. From a public health perspective, the hypothesis that depression risk is related to low VF is exciting because it suggests that easily acquired and potentially manipulable measures of heart rate variability could be used to assist in the early assessment of depression risk, and perhaps to develop interventions that operate directly upon the vagal pathway itself. PUBLIC HEALTH RELEVANCE: An important public health priority is the identification of factors that both increase individuals' vulnerability to depression and hinder recovery from this disorder. Abnormalities in cardiac vagal control may confer vulnerability to depression. This project will examine the hypothesis that depression risk is related to a lack of dynamic cardiac vagal control, which is potentially important because it suggests that easily acquired and potentially manipulable measures of heart rate variability could be used to assist in the early assessment of depression risk, and perhaps to develop interventions that operate directly upon the vagal pathway itself.