权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The Stress of Chronic Disease: Mineralocorticoid Mediation of Mood

慢性病的压力：盐皮质激素调节情绪

基本信息

批准号：
8584323
负责人：
ALAN Kim JOHNSON
金额：
$ 33.41万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8584323
关键词：
Abbreviations Address Adrenal Glands Aldosterone Anhedonia Animal Model Antidepressive Agents Arrhythmia Attenuated Behavior Behavioral Bibliography Brain Cardiac Output Cardiology Cardiovascular Physiology Cardiovascular system Characteristics Chronic Chronic Disease Comorbidity Data Depressed mood Development Disease Endocrine Event Frequencies Generations Heart Heart failure Hormonal Hormones Human Incidence Infarction Investigation Laboratory Rat Lead Mediation Mental Depression Methods Mineralocorticoid Receptor Mineralocorticoids Modeling Mood Disorders Moods Myocardial Infarction Nature Neuraxis Neurosciences Pathology Patients Physiological Play Probability Protocols documentation Psychopharmacology Recurrence Research Resources Role Selective Serotonin Reuptake Inhibitor Series Serotonin Signal Transduction Stimulus Stress Sudden Death Sympathetic Nervous System Syndrome System Testing Text Translating base biological adaptation to stress experience indexing interest pleasure pre-clinical pre-clinical research prophylactic psychologic public health relevance research study response reuptake stressor theories

项目摘要

DESCRIPTION (provided by applicant): Stressors exert an exacting toll when they are prolonged or varied and do not permit their target to mobilize appropriate or sufficient resources to attenuate the challenge. A characteristic of many chronic diseases is that throughout their prolonged course they generate neurohumoral signals intended to compensate for compromised physiological function, but they paradoxically generate additional disorders. The high incidence of the co-morbidity of heart failure and psychological depression may provide an example of how the product of the chronic physiological stress produced by a disease state gets translated into a second disorder. Recently we have been addressing the question of why there is such a high incidence of psychological depression accompanying heart failure. The results from several converging lines of evidence lead us to hypothesize that adrenal mineralocorticoids released in the course of attempting to maintain the cardiac output of a failing heart are depressivogenic through their action on the central nervous system. The present application proposes to test this hypothesis by studying the co-morbidity of heart failure and anhedonia, a cardinal sign of depressed mood, and by investigating the role of mineralocorticoids generated during heart failure in inducing the attenuated experience of pleasure. In addition, the role of mineralocorticoids themselves as depressivogenic agents will be investigated. The three specific aims to be achieved by the proposed research are to: 1) test experimental myocardial infarction-induced heart failure as a model for the co-morbidity of heart failure and depression, 2) investigate the role and mechanisms of mineralocorticoids in heart failure-induced depression, and 3) determine the role and mechanisms of mineralocorticoids as depressivogenic agents. Protocols employing methods from behavioral neuroscience, preclinical psychopharmacology, experimental cardiology, and cardiovascular physiology will be used to answer a series of key experimental questions. In the course of these studies a better understanding will be achieved of the 1) value of prophylactic use of selective serotonin reuptake inhibitors beginning early after myocardial infarction on heart failure-related depression, 2) likelihood that mineralocorticoids have a depressivogenic action on their own, and 3) potential antidepressant actions of mineralocorticoid receptor antagonists. Importantly, this preclinical research will test the feasibility of using a clinically approved mineralocorticoid receptor antagonist as an antidepressant pharmacotherapeutic.

描述（由申请人提供）：压力源在延长或变化时会产生严格的代价，并且不允许其目标调动适当或足够的资源来减轻挑战。许多慢性疾病的一个特征是，在其长期病程中，它们产生神经体液信号，旨在补偿受损的生理功能，但它们矛盾地产生额外的障碍。心力衰竭和心理抑郁的共病率很高，这可能提供了一个例子，说明由疾病状态产生的慢性生理应激产物如何转化为第二种疾病。最近，我们一直在探讨为什么伴随心力衰竭的心理抑郁发生率如此之高的问题。从几个汇聚的证据线的结果使我们假设，肾上腺盐皮质激素释放的过程中试图维持心输出量的衰竭的心脏是通过其对中枢神经系统的作用抑郁。本申请提出通过研究心力衰竭和快感缺乏（抑郁情绪的主要征兆）的共病，并通过研究心力衰竭期间产生的盐皮质激素在诱导减弱的快乐体验中的作用来测试该假设。此外，盐皮质激素本身作为抑郁剂的作用也将进行研究。本研究拟实现的三个具体目标是：1）测试实验性心肌梗死诱导的心力衰竭作为心力衰竭和抑郁症共病的模型，2）研究盐皮质激素在心力衰竭诱导的抑郁症中的作用和机制，3）确定盐皮质激素作为致抑郁剂的作用和机制。采用行为神经科学，临床前精神药理学，实验心脏病学和心血管生理学方法的协议将用于回答一系列关键的实验问题。在这些研究过程中，将更好地理解1）心肌梗死后早期开始预防性使用选择性5-羟色胺再摄取抑制剂对心力衰竭相关抑郁的价值，2）盐皮质激素本身具有致抑郁作用的可能性，3）盐皮质激素受体拮抗剂的潜在抗抑郁作用。重要的是，这项临床前研究将测试使用临床批准的盐皮质激素受体拮抗剂作为抗抑郁药的可行性。