Neural basis of interoceptive dysfunction and anxiety in anorexia nervosa

神经性厌食症内感受功能障碍和焦虑的神经基础

• 批准号: 10002264
• 负责人: SAHIB KHALSA
• 金额: $ 0.93万
• 依托单位: LAUREATE INSTITUTE FOR BRAIN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002264
• 关键词: Affect; Anorexia Nervosa; Anterior; Anxiety; Anxiety Disorders; Aversive Stimulus; Award; Behavior; Binge Eating; Biological Markers; Bipolar Disorder; Bolus Infusion; Brain; Bulimia; Cardiovascular system; Cerebrovascular Circulation; Clinical; Cognitive Therapy; Control Groups; Development; Disease; Double-Blind Method; Eating; Eating Behavior; Eating Disorders; Energy Intake; Environment; Epinephrine; Esthesia; Extinction (Psychology); Family member; Food; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Future; Generalized Anxiety Disorder; Goals; Hunger; Hypersensitivity; Image; Individual; Infusion procedures; Insula of Reil; Interoception; Intervention; Intravenous infusion procedures; Isoproterenol; Lead; Learning; Measures; Mental Health; Mental disorders; Mentorship; Methods; Modeling; Neurobiology; Neurosciences; Outcome; Patients; Perception; Peripheral; Pharmacology; Phenotype; Play; Process; Protocols documentation; Psychopathology; Public Health; Reporting; Research; Research Personnel; Role; Saline; Schizophrenia; Severity of illness; Signal Transduction; Somatosensory Cortex; Spin Labels; Sympathomimetics; System; Testing; Time; Training; Translating; Weight; Woman; Women' s Group; age group; anxiety treatment; anxious; base; brain circuitry; cingulate cortex; comorbidity; comparison group; effective therapy; experience; experimental study; food avoidance; health assessment; improved; indexing; insight; learning extinction; mortality; neural circuit; neuroimaging; novel; programs; reduced food intake; relating to nervous system; response; severe mental illness; signal processing; trait; weight restoration

PROJECT SUMMARY Anorexia nervosa (AN) is a serious mental illness with one of the highest mortality rates of all psychiatric disorders. It is characterized by reduced caloric intake, pre-meal anxiety and avoidance of food; behaviors that often persist after weight restoration. How the experience of eating provokes such anxiety in anorexia nervosa is unknown. Altered anxiety expression has been suggested as one explanation, on the basis that anxiety disorders are well known antecedents to AN, are frequently comorbid, and due to the increased aggregation of anxiety disorders among first degree family members of affected individuals. We propose that the altered processing of interoceptive signals is an important mechanism contributing to the expression of meal associated anxiety and dysfunctional eating behaviors in AN, and that determination of the processes contributing to this dysregulation will yield novel insights into the illness pathophysiology. To evaluate the neurobiological underpinnings of meal associated anxiety and interoception, the current proposal will investigate how individuals with AN experience cardiorespiratory sensations during meal anticipation relative to two control groups: age and weight-matched healthy comparison women, and an anxious comparison group of women with generalized anxiety disorder (GAD). Cardiorespiratory interoception and meal anxiety will be assessed using a validated protocol of intravenous infusions of isoproterenol and saline, during the pre-meal anticipatory time period. Isoproterenol, a rapid peripherally acting sympathomimetic agent, is a reliable method to measure changes in cardiorespiratory sensation and the double-blinded bolus infusion approach was developed by the PI. To understand the neural processes underlying this interoceptive phenotype the PI has successfully adapted the isoproterenol infusion paradigm to the functional MRI environment, and proposes using Arterial Spin Labeling (ASL) to identify cerebral blood flow changes associated with interoceptive stimulation. This pharmacological-fMRI (phMRI) approach is optimal for identifying changes in brain activity induced by peripherally induced sensation. Aims 1 and 2 of the research will identify which interoceptive biomarkers are similar and different between patients with AN and GAD. Once identified, these neural interoceptive biomarkers will be used to predict illness outcomes at one year, for each patient group (Aim 3). At the conclusion of these studies, we will know whether interoceptive-based biomarkers can be used as predictors of poor mental health outcomes in individuals with AN or GAD. Collectively, these findings will lay the groundwork for determining whether this approach can be translated into a novel treatment intervention for anxiety in AN, for example, by augmenting cognitive behavioral therapy with pre-meal interoceptive exposure training, to enhance inhibitory fear learning and reduce the fear of food in AN.

项目概要 神经性厌食症 (AN) 是一种严重的精神疾病，是所有精神疾病中死亡率最高的疾病之一 失调。其特点是热量摄入减少、餐前焦虑和回避食物；的行为 体重恢复后经常持续存在。饮食体验如何引发神经性厌食症患者的焦虑 未知。焦虑表达的改变被认为是一种解释，其基础是焦虑 众所周知，这些疾病是 AN 的前因，并且经常合并发病，并且由于 受影响个体的一级家庭成员中存在焦虑症。我们建议修改后的 内感受信号的处理是促进膳食表达的重要机制 AN 中相关的焦虑和功能失调的饮食行为，以及过程的确定 造成这种失调的原因将产生对疾病病理生理学的新见解。评估 进餐相关焦虑和内感受的神经生物学基础，目前的提案将 调查 AN 患者在进食预期期间如何体验心肺感觉 两个对照组：年龄和体重匹配的健康对照女性，以及焦虑对照组 患有广泛性焦虑症（GAD）的女性。心肺内感受和进餐焦虑将 使用经过验证的餐前静脉输注异丙肾上腺素和盐水方案进行评估 预期时间段。异丙肾上腺素是一种快速外周作用的拟交感神经药，是一种可靠的方法 为了测量心肺感觉的变化，双盲推注方法是 由 PI 开发。为了理解这种内感受表型背后的神经过程，PI 成功地将异丙肾上腺素输注范式适应功能性 MRI 环境，并提出 使用动脉旋转标记 (ASL) 来识别与内感受相关的脑血流变化 刺激。这种药理学功能磁共振成像 (phMRI) 方法最适合识别大脑活动的变化 由外周感应引起。研究的目标 1 和 2 将确定哪种内感受 AN 和 GAD 患者的生物标志物既相似又不同。一旦识别出来，这些神经元 内感受生物标志物将用于预测每个患者组一年后的疾病结果（目标 3）。在 根据这些研究的结论，我们将知道基于内感受的生物标志物是否可以用作 AN 或 GAD 患者心理健康状况不佳的预测因素。总的来说，这些发现将奠定 确定这种方法是否可以转化为新型治疗干预措施的基础 例如，通过餐前内感受暴露增强认知行为疗法来治疗 AN 中的焦虑 训练，以增强抑制性恐惧学习并减少 AN 中对食物的恐惧。