Affective Consequences of Chemotherapy

化疗的情感后果

• 批准号: 8989060
• 负责人: Anne Courtney DeVries
• 金额: $ 42.51万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8989060
• 关键词: Adrenal Cortex Hormones; Affect; Affective; Affective Symptoms; Anti-Inflammatory Agents; Anti-inflammatory; Anxiety; Behavior; Behavioral; Biological; Biological Process; Breast Cancer Patient; Breast Cancer survivor; Buffers; Cancer Patient; Corticosterone; Data; Depressed mood; Detection; Development; Diagnosis; Disease; Employee Strikes; Environmental Risk Factor; Etiology; General Population; Glucocorticoid Receptor; Glucocorticoids; Goals; Immune; Immune system; Incidence; Individual; Individual Differences; Inflammation; Inflammatory Response; Lead; Length; Link; Mediating; Mental Depression; Mental Health; Methods; Mood Disorders; Mus; Oxytocin; Oxytocin Receptor; Pathway interactions; Patients; Personal Satisfaction; Physiological; Population; Predisposition; Prevention; Psyche structure; Quality of life; Reporting; Research; Resected; Risk; Social Environment; Social Interaction; Social isolation; Stress; Survival Rate; Survivors; Testing; Time; United States; Woman; anxiety symptoms; anxiety-like behavior; behavior change; biobehavior; cancer diagnosis; cancer recurrence; chemotherapy; depressive symptoms; improved; insight; malignant breast neoplasm; neuroinflammation; novel; patient population; physical conditioning; public health relevance; research study; response; social; treatment planning; tumor

 DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed cancer in women; 1 in 8 women in the United States will be diagnosed with this disease during their lifetime. Advances in detection and treatment have substantially increased the 5-year survival rate for breast cancer patients. However, among this population of survivors, the incidences of depression and anxiety are approximately 3-5 times higher than among women in the general population. Despite this striking increase, the etiology of depression and anxiety among breast cancer patients remains unknown. In mice, we have been able to establish a causal link between chemotherapy-induced neuroinflammation and changes in affective behavior. The first goal of this proposal is to determine whether having a tumor that has been resected primes the inflammatory response to chemotherapy and to determine how neuroinflammation and affective behavior change over the course of multiple chemotherapy treatments. The second goal of this proposal is to determine whether factors that are hypothesized to contribute to individual differences in susceptibility to the development of depression and anxiety after chemotherapy, specifically stress and social isolation, do so by increasing the proinflammatory consequences of chemotherapy. Our preliminary data indicate that stress exposure and social isolation significantly increase depressive-like behavior and anxiety-like behavior, respectively, among mice treated with chemotherapy. The experiments in Aim 2 will determine whether the chemotherapy-induced exacerbation of depressive-like behavior is achieved through a mechanism involving corticosteroid mediated increases in neuroinflammation, and whether blocking the glucocorticoid response to stress reduces the neuroinflammatory and affective consequences of chemotherapy. The experiments in Aim 3 will determine whether affiliative social interaction provides a buffer against chemotherapy-induced neuroinflammation, and affective changes. The proposed research represents the first experimental test of the hypothesis that modulation of chemotherapy-induced neuroinflammation alters the risk of developing depression and anxiety. The long-range goal of the proposed research is to improve the mental and physical health of cancer patients, as well as their quality of life, through the alleviation of depression and anxiety. The important first stp in achieving this goal is improved understanding of the biological processes through which environmental factors influence susceptibility to chemotherapy-related affective disorders.

 描述（由适用提供）：乳腺癌是女性最常见的癌症；在美国，有八分之一将在其一生中被诊断出患有这种疾病。检测和治疗的进展大大提高了乳腺癌患者的5年生存率。但是，在这种生存人群中，抑郁和焦虑的发生率约为一般人群中女性的3-5倍。尽管有惊人的增加，但乳腺癌患者的抑郁和焦虑病因仍然未知。在小鼠中，我们能够在化学疗法诱导的神经炎症和情感行为变化之间建立催化联系。该提案的第一个目标是确定是否已切除了肿瘤对化学疗法的炎症反应，并确定在多种化疗治疗过程中神经炎症和情感行为如何变化。该提案的第二个目标是确定假设的因素是否导致化学疗法后抑郁症和焦虑症的易感性的个体差异，特别是压力和社会隔离，这是通过增加化学疗法的促进性后果来做到的。我们的初步数据表明，在接受化学疗法治疗的小鼠中，压力暴露和社会隔离分别显着增加了类似抑郁的行为和焦虑行为。 AIM 2中的实验将确定化学疗法诱导的抑郁样行为的加剧是否通过涉及皮质类固醇介导的神经炎症的增加以及阻断糖皮质激素对胁迫的反应减少神经炎和化学疗法的情感后果的机制是否实现了抑郁样行为。 AIM 3中的实验将确定会员社会相互作用是否为化学疗法引起的神经炎症和情感变化提供缓冲。拟议的研究代表了对化疗诱导的神经炎症的调节的第一次实验检验，这会改变抑郁症和焦虑的风险。拟议的研究的远程目标是通过缓解抑郁症和焦虑来改善癌症患者以及他们的生活质量的心理和身体健康。实现这一目标的重要第一个STP是对生物学过程的理解得以提高，环境因素会影响与化学疗法相关的情感障碍的易感性。