Behavioral autonomic and endocrine regulation in depression and heart disease

抑郁症和心脏病的行为自主神经和内分泌调节

• 批准号: 7752579
• 负责人: ANGELA J GRIPPO
• 金额: $ 16.31万
• 依托单位: NORTHERN ILLINOIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7752579
• 关键词: Affect; Affective Symptoms; Aging; Anhedonia; Animal Model; Anxiety; Applications Grants; Autonomic nervous system; Behavior; Behavioral; Biological Models; Brain; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Data; Depressive Syndromes; Development; Disease; Dose; Endocrine; Exploratory/Developmental Grant; Family history of; Functional disorder; Heart Diseases; Heart Rate; Hormones; Human; Individual; Laboratories; Lead; Link; Mammals; Measures; Mediating; Modeling; Mood Disorders; Moods; Neuraxis; Neuropeptides; Neurosecretory Systems; Oxytocin; Patients; Persons; Physiological; Physiological Processes; Physiology; Play; Population; Process; Reaction; Recording of previous events; Regulation; Research; Research Project Grants; Research Proposals; Risk Factors; Rodent; Rodent Model; Role; Social Behavior; Social Environment; Social isolation; Stress; Testing; Ventricular Arrhythmia; behavior test; depression; depressive symptoms; effective therapy; experience; heart rate variability; neuromechanism; novel; peptide hormone; prairie vole; prevent; programs; psychologic; research study; response; social; social stress; stress management; stressor

DESCRIPTION (provided by applicant): This research will use behavioral, autonomic, and neuroendocrine approaches to investigate the hypothesis that neural mechanisms involving oxytocin underlie the documented association between depression and heart disease. Disorders relating to negative affect, such as depression and anxiety, are recognized risk factors for cardiovascular disease; this relationship is especially important for individuals with specific vulnerabilities (such as persons with a family history of heart disease or aging populations). Psychological and physiological responses to stressors, and in particular reactions in the social context, play an important role in the development of affective symptoms and behaviors, and have been linked directly to cardiovascular dysfunction. Furthermore, evidence indicates that oxytocin mediates behavioral and physiological processes associated with stress and social experiences, and therefore this neuropeptide may have a mechanistic role in the link between mood and cardiovascular disorders. The current research project will use a rodent model, the socially monogamous prairie vole, to study the behavioral, neuroendocrine, and autonomic responses to a social stressor (social isolation), and the potential oxytocinergic mechanisms that underlie these responses. Converging evidence suggests that the prairie vole provides a unique model system for studying responsiveness to social experiences, and that this species has utility for studying autonomic mechanisms related to mood and cardiac function. Experiment 1 will employ (a) behavioral tests relevant to depression, (b) continuous recording of autonomic and cardiac parameters, and (c) measures of circulating and central nervous system hormones and peptides, to test the hypothesis that social isolation induces behavioral and physiological responses relevant to depression and cardiovascular disease (Specific Aim 1). Experiment 2 will employ (a) chronic administration of oxytocin and (b) administration of an oxytocin antagonist, to test the hypothesis that oxytocinergic mechanisms underlie specifically the behavioral, autonomic, and neuroendocrine responses to social isolation (Specific Aim 2). This research proposes a novel mechanism by which the social environment impacts behavior, physiology, and brain function, which can promote the development of more comprehensive treatments for patients with depression and cardiovascular disease. There are important interactions among behavior, brain function, and the cardiovascular system; one such example of these interactions is the association between depression and heart disease. The current research project will investigate directly the link between these conditions by studying in an animal model the behavioral, endocrine (hormones), autonomic (control of cardiovascular function), and brain processes involved in mediating mood and cardiovascular function. This research can lead to the development of more effective treatments for patients with depression and heart disease.

描述（由申请人提供）：这项研究将使用行为，自主神经和神经内分泌方法来研究涉及催产素的神经机制是抑郁症与心脏病之间有记录的关联的假设。与负面影响有关的疾病，例如抑郁和焦虑，是心血管疾病的公认危险因素。这种关系对于具有特定脆弱性的个体（例如患有心脏病的家族病史或衰老的人）尤其重要。对压力源的心理和生理反应，尤其是在社会背景下的反应，在情感症状和行为的发展中起着重要作用，并与心血管功能障碍直接相关。此外，证据表明催产素介导了与压力和社会经历相关的行为和生理过程，因此该神经肽在情绪与心血管疾病之间的联系中可能具有机械作用。当前的研究项目将使用啮齿动物模型，即社会一夫一妻制的草原vole，研究对社会压力源（社会隔离）的行为，神经内分泌和自主反应，以及潜在的催产机制，这些机制是这些反应的基础。融合的证据表明，草原vole提供了一个独特的模型系统，用于研究对社会经验的反应性，并且该物种具有研究与情绪和心脏功能相关的自主机制的实用性。实验1将采用（a）与抑郁症相关的行为测试，（b）自主和心脏参数的连续记录，以及（c）循环和中枢神经系统激素和肽的衡量，以测试社会隔离会导致行为和生理反应与抑郁症和心血管疾病相关的假设（特定目标1）。实验2将采用（a）长期施用催产素和（b）催产素拮抗剂，以检验以下假设：催产蛋白机制具体是行为，自主神经和神经内分泌对社会隔离的反应（特定目标2）。这项研究提出了一种新的机制，通过这种机制，社会环境会影响行为，生理和大脑功能，该机制可以促进为抑郁症和心血管疾病患者开发更全面的治疗方法。行为，大脑功能和心血管系统之间存在重要的相互作用。这些相互作用的一个例子是抑郁症与心脏病之间的关联。当前的研究项目将通过在动物模型中研究行为，内分泌（激素），自主神经（心血管功能的控制）以及涉及介导情绪和心血管功能涉及的大脑过程来直接研究这些条件之间的联系。这项研究可以导致为患有抑郁症和心脏病的患者开发更有效的治疗方法。

项目成果

The effects of environmental enrichment on depressive and anxiety-relevant behaviors in socially isolated prairie voles.

• DOI: 10.1097/psy.0000000000000052
• 发表时间: 2014-05
• 期刊: Psychosomatic medicine
• 影响因子: 3.3
• 作者: Grippo AJ;Ihm E;Wardwell J;McNeal N;Scotti MA;Moenk DA;Chandler DL;LaRocca MA;Preihs K
• 通讯作者: Preihs K

Disruption of social bonds induces behavioral and physiological dysregulation in male and female prairie voles.

• DOI: 10.1016/j.autneu.2013.10.001
• 发表时间: 2014-02
• 期刊: AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
• 影响因子: 2.7
• 作者: McNeal, Neal;Scotti, Melissa-Ann L.;Wardwell, Joshua;Chandler, Danielle L.;Bates, Suzanne L.;LaRocca, Meagan;Trahanas, Diane M.;Grippo, Angela J.
• 通讯作者: Grippo, Angela J.

Altered Connexin 43 and Connexin 45 protein expression in the heart as a function of social and environmental stress in the prairie vole.

• DOI: 10.3109/10253890.2014.979785
• 发表时间: 2015-01
• 期刊: Stress (Amsterdam, Netherlands)
• 作者: Grippo AJ;Moffitt JA;Henry MK;Firkins R;Senkler J;McNeal N;Wardwell J;Scotti MA;Dotson A;Schultz R
• 通讯作者: Schultz R

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease.

草原田鼠的长期社会隔离会导致内皮功能障碍：对抑郁症和心血管疾病的影响。

• DOI: 10.1016/j.physbeh.2012.03.019
• 发表时间: 2012
• 期刊: Physiology & behavior
• 影响因子: 2.9
• 作者: Peuler,JacobD;Scotti,Melissa-AnnL;Phelps,LauraE;McNeal,Neal;Grippo,AngelaJ
• 通讯作者: Grippo,AngelaJ

Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles.

• DOI: 10.1016/j.autneu.2010.03.003
• 发表时间: 2010-08-25
• 期刊: AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
• 影响因子: 2.7
• 作者: Grippo, Angela J.;Sgoifo, Andrea;Mastorci, Francesca;McNeal, Neal;Trahanas, Diane M.
• 通讯作者: Trahanas, Diane M.