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.

项目摘要 神经性厌食症是一种严重的精神疾病，在所有精神疾病中死亡率最高 紊乱其特征是热量摄入减少，餐前焦虑和避免食物;行为， 通常在体重恢复后仍然存在。进食的经历如何引起神经性厌食症患者的焦虑 不明改变的焦虑表达被认为是一种解释，其基础是焦虑 这些疾病是AN的众所周知的前因，经常是共病的，并且由于AN的聚集增加， 受影响个体的一级家庭成员中的焦虑症。我们建议， 内感受信号的处理是一个重要的机制，有助于表达膳食 相关的焦虑和功能失调的饮食行为，以及确定的过程， 对这种失调的贡献将产生对疾病病理生理学的新见解。评价 神经生物学基础的膳食相关的焦虑和内感受，目前的建议将 研究AN患者在进餐预期期间如何体验心肺感觉， 两个对照组：年龄和体重相匹配的健康对照妇女，以及焦虑对照组， 广泛性焦虑症（GAD）呼吸道内感受和进餐焦虑 使用餐前静脉输注异丙肾上腺素和生理盐水的经验证方案进行评估 预期时间段。异丙肾上腺素是一种快速的外周作用的拟交感神经药， 测量心肺感觉的变化，双盲推注方法是 由PI开发。为了了解这种内感受性表型背后的神经过程，PI 成功地适应了异丙肾上腺素输注范例的功能磁共振成像环境，并提出 使用动脉自旋标记（ASL）来识别与内感受性相关的脑血流变化， 刺激.这种药理学功能磁共振成像（phMRI）方法是识别大脑活动变化的最佳方法 由外周诱发的感觉引起的。研究的目的1和2将确定哪些内感受性 AN和GAD患者之间的生物标志物相似且不同。一旦确定，这些神经 对于每个患者组，内感受性生物标志物将用于预测一年时的疾病结果（目标3）。在 这些研究的结论，我们将知道是否可以使用基于内感受性的生物标志物作为 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的治疗干预的基础， 例如，通过餐前内感受性暴露增强认知行为治疗， 训练，以增强抑制性恐惧学习，减少对AN食物的恐惧。