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.

项目总结 神经性厌食症是一种严重的精神疾病，在所有精神科疾病中死亡率最高。 精神错乱。它的特点是卡路里摄入量减少，餐前焦虑和避免食物；行为 通常在体重恢复后仍会持续。进食体验如何引发神经性厌食症患者的焦虑 是未知的。焦虑表达的改变被认为是一种解释，因为焦虑 众所周知，疾病是AN的前驱因素，经常并存，这是由于 受影响个人的一级家庭成员中的焦虑症。我们建议更改后的 内感信号的加工是影响Meal表达的重要机制 与焦虑和进食功能障碍相关的AN行为及其过程的确定 促成这种失调将对疾病的病理生理学产生新的见解。要评估 饮食相关焦虑和内感的神经生物学基础，目前的提案将 调查在进餐预期期间有心肺感觉的个体如何与 两个对照组：年龄和体重匹配的健康对照女性，以及焦虑的对照组 患有广泛性焦虑障碍(GAD)的女性。心肺内感和进食焦虑将是 在餐前使用有效的静脉输注异丙肾上腺素和生理盐水的方案进行评估 预期时间段。异丙肾上腺素是一种快速起作用的外周交感神经刺激剂，是一种可靠的治疗方法 为了测量心肺感觉的变化和双盲团注方法， 由PI开发。为了理解这种内感表型背后的神经过程，PI具有 成功地将异丙肾上腺素输注范例适应于功能磁共振环境，并提出了 应用动脉自旋标记(ASL)识别与内感相关的脑血流变化 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。 由外周诱导的感觉引起的。研究的目标1和目标2将确定哪种内感受器 AN和GAD患者的生物标志物既相似又不同。一旦确定，这些神经 对于每个患者组，将使用相互感受生物标志物来预测一年后的疾病结果(目标3)。在… 这些研究的结论，我们将知道基于内感的生物标志物是否可以作为 患有AN或GAD的个体心理健康状况不良的预测因子。总的来说，这些发现将奠定 确定这种方法是否可以转化为一种新的治疗干预措施的基础是 例如，通过增加餐前内感暴露的认知行为疗法来缓解焦虑 训练，增强抑制性恐惧学习，减少对食物的恐惧。