Biomarkers of Interoceptive Awareness in Adolescent Anorexia Nervosa

青少年神经性厌食症内感受意识的生物标志物

• 批准号: 7938798
• 负责人: KEVIN S LABAR
• 金额: $ 49.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938798
• 关键词: Acute; Adolescence; Adolescent; Age; Anorexia Nervosa; Anterior; Anxiety Disorders; Area; Arousal; Attention; Awareness; Biofeedback; Biological; Biological Markers; Brain; Brain region; Butterflies; Cessation of life; Conscious; Coupling; Decision Making; Development; Diagnosis; Disease; Dorsal; Eating Disorders; Emotional; Esthesia; Exhibits; Feedback; Feeling; Functional Magnetic Resonance Imaging; Hypersensitivity; Individual; Individual Differences; Intervention; Laboratories; Learning; Link; Measures; Memory; Mental disorders; Modification; Outcome Study; Performance; Prize; Psychophysiology; Reaction Time; Recording of previous events; Relative (related person); Reporting; Risk; Role; Sampling; Shapes; Short-Term Memory; Signal Transduction; Starvation; Stomach; Suicide; Symptoms; Time; Uncertainty; Upper digestive tract structure; Validation; Visceral; Weight; Woman; aversive conditioning; body-mind; cell motility; cohort; critical period; disability; emotional experience; experience; flexibility; gastrointestinal symptom; improved; mortality; neural circuit; neural patterning; neuroimaging; novel; public health relevance; relating to nervous system; response; restoration; simulation; sobriety; statistics; trait

DESCRIPTION (provided by applicant): (03) Biomarker Discovery and Validation general challenge Area and the 03-MH-101 Biomarkers in mental disorders specific challenge topic. Anorexia nervosa (AN) is a terrifying and perplexing disorder. Eating disorders, in general, rank among the top ten causes for disability among women, while AN has the highest mortality rate of any psychiatric disorder with a 57 fold increased risk of death due to suicide relative to an age- matched cohort. Despite these sobering statistics, one of the greatest mysteries of AN is that the ill state is prized by the individuals afflicted with this disorder. They report 'feeling better' while starved. In contrast, prior to the ill state, the majority with AN are diagnosed with an anxiety disorder and experience elevated levels of gastrointestinal symptoms, - conditions associated with increased visceral sensitivity. Notably, the severe starvation of AN principally onsets during adolescence, a vulnerable period of neural maturation and modification. Indeed, the course of AN is notable for a 'critical period' of intervention. The likelihood of improvement in symptoms of AN diminishes markedly if aggressive treatment is not undertaken during the vulnerable developmental window of early to middle adolescence. This body of evidence suggests that sensitivity to change in the internal state of the body (i.e. interoceptive sensitivity) exists premorbidly in those with AN, that biological alterations during adolescence may potentiate somatic sensitivity, that starvation during this period may dampen somatic experience, and that critical alterations in brain neural circuitry during this period may be crucial in shaping disorder course. In a sample of 75 adolescents (25 in the acute state of malnourishment of anorexia nervosa, 25 weight-restored from anorexia nervosa, and 25 typically developing controls), we will complete the following aims. We will: 1) characterize differences in interoceptive signaling from the upper GI tract and the interoceptive cortex, 2) characterize the differences in prefrontal cortical modulation of interoceptive cortex, and 3) characterize differences in the role of orbitofrontal cortex on modulation of cortical activity and connectivity with interoceptive cortex. By studying patterns of neural activation and psychophysical response that alter as a function of starvation and are associated with interoceptive sensitivity, we can formulate novel hypotheses on biological changes associated with starvation that are reinforcing for this group and derive novel treatment targets. PUBLIC HEALTH RELEVANCE STATEMENT: Anorexia nervosa (AN) is a terrifying and perplexing disorder. Eating disorders, in general, rank among the top ten causes for disability among women, while AN has the highest mortality rate of any psychiatric disorder with a 57 fold increased risk of death due to suicide relative to an age-matched cohort. Despite these sobering statistics, one of the greatest mysteries of AN is that the ill state is prized by the individuals afflicted with this disorder. They report 'feeling better' while starved. In contrast, prior to the ill state, the majority with AN are diagnosed with an anxiety disorder and experience elevated levels of gastrointestinal symptoms, - conditions associated with increased sensitivity to body changes (e.g. sensing the pit in your gut when you have done something wrong or the butterflies in your gut when you are worried about something). In fact, sensitivity to these internal sensations (called interoceptive sensitivity) has profound implications well beyond anorexia nervosa. Interoceptive sensitivity is associated with the strength of emotional memories, the depth with which we can understand others, and may be associated with the strength of emotional learning. As adolescence is a time of profound brain and body change, this developmental period may be a key window to study how individuals differ in this sensitivity and the boundaries that define pathological development. In fact, the severe starvation of AN principally begins during adolescence. Thus, malnourishment during this period may have particularly profound negative effects. In fact, the course of AN is notable for a 'critical period' of intervention. The likelihood of improvement in symptoms of AN diminishes markedly if aggressive treatment is not undertaken during the vulnerable developmental window of early to middle adolescence. Using functional neuroimaging we will examine neural circuits in the brain that may help us to identify brain regions that may contribute to difficulties with sensitivity to internal bodily states in those with anorexia nervosa and how these differ from typically developing adolescents. By studying patterns of neural activation and psychophysical response that alter as a function of starvation and are associated with interoceptive sensitivity, we can formulate novel hypotheses on biological changes associated with starvation that are reinforcing for this group and derive novel treatment targets for those with anorexia nervosa and better understand the transitioning mind-body connection of adolescence.

描述（由申请人提供）： (03) 生物标志物发现和验证一般挑战领域和 03-MH-101 精神障碍生物标志物特定挑战主题。 神经性厌食症（AN）是一种令人恐惧且令人困惑的疾病。一般来说，饮食失调是导致女性残疾的十大原因之一，而 AN 的死亡率是所有精神疾病中最高的，与年龄匹配的人群相比，自杀导致的死亡风险增加了 57 倍。尽管有这些发人深省的统计数据，但 AN 最大的谜团之一是，患有这种疾病的个人很珍视这种疾病状态。他们报告说，饥饿时“感觉好多了”。相比之下，在患病之前，大多数 AN 患者被诊断患有焦虑症，并且胃肠道症状水平升高，这些症状与内脏敏感性增加相关。值得注意的是，AN 的严重饥饿主要发生在青春期，这是神经成熟和修饰的脆弱时期。事实上，AN 的病程因干预的“关键期”而引人注目。如果在青春期早期到中期的脆弱发育窗口期不采取积极治疗，AN 症状改善的可能性就会显着降低。这些证据表明，AN 患者病前就存在对身体内部状态变化的敏感性（即内感受敏感性），青春期的生物变化可能会增强躯体敏感性，这一时期的饥饿可能会抑制躯体体验，并且这一时期大脑神经回路的关键改变可能对疾病进程的形成至​​关重要。在 75 名青少年的样本中（25 名处于神经性厌食症急性营养不良状态，25 名从神经性厌食症恢复体重，25 名正常发育对照），我们将完成以下目标。我们将：1）表征来自上胃肠道和内感受皮层的内感受信号的差异，2）表征内感受皮层的前额皮质调节的差异，以及3）表征眶额皮质在皮质活动调节中的作用的差异与内感受皮层的连接。通过研究随饥饿而变化并与内感受敏感性相关的神经激活和心理物理反应模式，我们可以对与饥饿相关的生物变化提出新的假设，这些假设对这一群体有强化作用，并得出新的治疗目标。 公共卫生相关声明：神经性厌食症 (AN) 是一种令人恐惧且令人困惑的疾病。一般来说，饮食失调是导致女性残疾的十大原因之一，而 AN 的死亡率是所有精神疾病中最高的，与年龄匹配的人群相比，自杀导致的死亡风险增加了 57 倍。尽管有这些发人深省的统计数据，但 AN 最大的谜团之一是，患有这种疾病的个体很珍视这种疾病状态。他们报告说，饥饿时“感觉好多了”。相比之下，在患病之前，大多数 AN 患者都被诊断出患有焦虑症，并且胃肠道症状水平升高， - 与对身体变化的敏感性增加相关的情况（例如，当您做错事时感觉到肠道凹陷）或者当你担心某事时你内心的蝴蝶）。事实上，对这些内部感觉的敏感性（称为内感受敏感性）的深远影响远远超出了神经性厌食症。内感受敏感性与情绪记忆的强度、我们理解他人的深度有关，并且可能与情绪学习的强度有关。由于青春期是大脑和身体发生深刻变化的时期，因此这个发育时期可能是研究个体在这种敏感性方面有何不同以及定义病理发育的界限的关键窗口。事实上，AN的严重饥饿主要开始于青春期。因此，这一时期的营养不良可能会产生特别深远的负面影响。事实上，AN 的病程以干预的“关键期”而著称。如果在青春期早期到中期的脆弱发育窗口期不采取积极治疗，AN 症状改善的可能性就会显着降低。使用功能性神经影像学，我们将检查大脑中的神经回路，这可能有助于我们识别可能导致神经性厌食症患者对内部身体状态敏感困难的大脑区域，以及这些区域与正常发育的青少年有何不同。通过研究随饥饿而改变并与内感受敏感性相关的神经激活和心理物理反应模式，我们可以对与饥饿相关的生物学变化提出新的假设，这些假设对这一群体有强化作用，并为神经性厌食症患者得出新的治疗目标并更好地了解青春期身心转变的联系。