Neurobiological and Behavioral Risk Mechanisms of Youth Avoidant/Restrictive Eating Trajectories

青少年回避/限制性饮食轨迹的神经生物学和行为风险机制

• 批准号: 10120795
• 负责人: Elizabeth Austen Lawson
• 金额: $ 8.4万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-15 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10120795
• 关键词: Acute; Administrative Supplement; Adolescence; Age; Agonist; Amygdaloid structure; Anorexia Nervosa; Anxiety; Appetite Stimulants; Arousal; Award; Behavior; Behavioral; Behavioral Research; Biomedical Research; Biometry; Birth; Blood; Brain-Derived Neurotrophic Factor; Categories; Child; Child Psychiatry; Childhood; Choking; Cholecystokinin; Chronic; Clinical; Clinical Psychology; DSM-V; Data; Desire for food; Detection; Dimensions; Discrimination; Disease; Eating; Eating Disorders; Endocrinology; Event; Fasting; Food; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Galvanic Skin Response; Growth; Heart Rate; Homeostasis; Hormones; Hunger; Hydrocortisone; Hypothalamic structure; Impairment; Individual; Insula of Reil; Intake; International; Intervention; Investigation; Life; Light; Literature; Malnutrition; Medical; Mental disorders; Mind; Modeling; Negative Valence; Neurobiology; Neurosecretory Systems; Odors; Outcome; Oxytocin; Parents; Patient Self-Report; Pediatrics; Peptide YY; Perception; Phenotype; Phobias; Physiology; Prevention; Psychopathology; Public Health; Research Domain Criteria; Research Project Grants; Risk; Satiation; Sensory; Severities; Shapes; Signal Transduction; Site; Sum; Symptoms; Taste Perception; Therapeutic Intervention; Time; United States National Institutes of Health; Vomiting; Weight; Work; Youth; aged; avoidant restrictive food intake disorder; boys; brain behavior; cognitive system; cohort; cost; disease classification; feeding; food avoidance; food restriction; ghrelin; girls; imaging genetics; innovation; interest; multidisciplinary; neuroimaging; nutrition; outcome prediction; parent grant; potential biomarker; prospective; psychiatric symptom; psychosocial; recruit; response; restrictive eating; sex; targeted treatment; trait

ABSTRACT Avoidant and restrictive eating is common across youth mental health disorders, and is prospectively associated with poor growth, nutritional deficiencies, psychiatric symptoms, and psychosocial impairment. The newly introduced DSM-5 Avoidant/Restrictive Food Intake Disorder includes some (but not all) avoidant and restrictive eating presentations. Initial evidence suggests that avoidant and restrictive eating is highly heterogeneous, with poor intake characterized by choking or vomiting phobias; loss of interest in feeding; and/or extreme food selectivity. Moreover, very little is known about its pathophysiology or long- term outcomes. Our study will leverage unique and complementary contributions of an international team with expertise in clinical psychology, child psychiatry, pediatrics, endocrinology, biostatistics and functional neuroimaging to investigate risk mechanisms and longitudinal outcomes of avoidant and restrictive eating. We will establish a clinical cohort of children aged 8-18 years (n=100) and healthy controls (n=50) matched for sex, age, and Tanner stage to investigate how, across units of analysis, RDoC constructs contribute to avoidant and restrictive eating. First, we hypothesize that Negative Valence (acute threat/fear) over-activity (circuits: amygdala activation during a validated fear paradigm; hormones: cortisol and oxytocin; physiology: heart rate and skin conductance; self report: fear and trait anxiety) will correlate with phobic features. Second, we hypothesize that Arousal/Regulatory (homeostasis) dysfunction (circuits: hypothalamus and insula hypoactivation during a validated food paradigm; hormones: PYY, CKK, BDNF; self report: hunger and fullness) will correlate with low-appetite features. Third, we will explore Cognitive Systems (perception) over-sensitivity (circuits: hyperactivation in primary taste cortex during a taste paradigm; hormones: PYY; self report: sensory profile; behavior: taste and odor threshold, discrimination, and detection; physiology: taste perception) and its correlation with sensory features. We expect that the clinical cohort will have greater dysfunction across these 3 constructs than controls. We will then use latent class factor models to determine whether avoidant/restrictive eating comprises multiple distinct phenotypes (as prior literature assumes) or a single phenotype with 3 overlapping dimensions (as we hypothesize). We will follow our clinical cohort for 2 years to evaluate a) the persistence of avoidant/restrictive eating, growth, and psychopathology outcomes; and b) if dysfunction in all 3 RDoC constructs predicts outcomes. This study will be innovative and unique in 3 ways: 1) by providing an empirical investigation of an understudied clinical presentation; 2) by providing the first investigation of pathophysiology and risk mechanisms; and 3) by characterizing poorly understood longitudinal outcomes. In sum, conceptualizing avoidant/restrictive eating within an RDoC framework that integrates mind, brain, and behavior has great potential to reduce the burden of feeding disorders by informing nosology, treatment, and prevention.

抽象的 避免和限制性饮食在青年心理健康障碍中很常见，并且前景是 与生长不良，营养缺陷，精神病症状和社会心理障碍有关。 新引入的DSM-5回避/限制性食物摄入障碍包括一些（但不是全部） 回避和限制性饮食介绍。最初的证据表明，回避和限制性饮食是 高度异质，摄入量很差，其特征是窒息或呕吐恐惧症；失去兴趣 进食；和/或极端的食物选择性。而且，关于其病理生理学或长期的知之甚少 术语成果。我们的研究将利用国际团队的独特和互补贡献 具有临床心理学，儿童精神病学，儿科，内分泌学，生物统计学和功能方面的专业知识 神经影像学研究风险机制和避免饮食的纵向结局。 我们将建立一个8-18岁儿童（n = 100）和健康对照（n = 50）的临床队列 匹配性别，年龄和制革商阶段，以研究RDOC构造的分析单位如何 有助于回避和限制性饮食。首先，我们假设负面价（急性威胁/恐惧） 过度活动性（电路：经过验证的恐惧范式中的杏仁核激活；激素：皮质醇和 催产素;生理学：心率和皮肤电导；自我报告：恐惧和特质焦虑）将与 恐惧功能。其次，我们假设唤醒/调节性（稳态）功能障碍（电路： 经过验证的食物范式期间的下丘脑和岛裂次激活；激素：PYY，CKK，BDNF； 自我报告：饥饿和饱腹）将与低苹果特征相关。第三，我们将探索认知 系统（感知）过度敏感（电路：味道中原发性皮层的过度激活 范例;激素：PYY；自我报告：感觉概况；行为：味道和气味阈值，歧视， 和检测；生理学：味觉感知）及其与感觉特征的相关性。我们期望 临床队列在这三个构建体中的功能障碍将比对照更大。然后我们将使用潜在 班级因素模型以确定避免/限制性饮食是否包括多种不同的表型 （如先前的文献所假定）或具有3个重叠维度的单个表型（正如我们假设的那样）。我们 将遵循我们的临床队列2年来评估a）回避/限制性饮食，生长， 和心理病理学结果； b）如果所有3个RDOC构建体中的功能障碍都可以预测结果。 这项研究将以三种方式具有创新性和独特性：1）通过对 研究了临床表现； 2）通过提供病理生理学和风险的首次研究 机制； 3）表征纵向结果鲜为人知。总而言之，概念化 在整合思想，大脑和行为的RDOC框架内的回避/限制性饮食 通过告知疾病，治疗和预防，减轻喂养障碍的负担的潜力。

项目成果

The factor structure and validity of a diagnostic interview for avoidant/restrictive food intake disorder in a sample of children, adolescents, and young adults.

• DOI: 10.1002/eat.23792
• 发表时间: 2022-11
• 期刊: INTERNATIONAL JOURNAL OF EATING DISORDERS
• 影响因子: 5.5
• 作者: Cooper-Vince, Christine E.;Nwaka, Chika;Eddy, Kamryn T.;Misra, Madhusmita;Hadaway, Natalia A.;Becker, Kendra R.;Lawson, Elizabeth A.;Cooke, Lucy;Bryant-Waugh, Rachel;Thomas, Jennifer J.;Micali, Nadia
• 通讯作者: Micali, Nadia

Some of the burden of eating disorders is still hidden.

• DOI: 10.1016/s2215-0366(21)00080-8
• 发表时间: 2021-04
• 期刊: LANCET PSYCHIATRY
• 影响因子: 64.3
• 作者: Thomas, Jennifer J.;Becker, Kendra R.
• 通讯作者: Becker, Kendra R.

Preliminary validation of the pica, ARFID and rumination disorder interview ARFID questionnaire (PARDI-AR-Q).

• DOI: 10.1186/s40337-022-00706-7
• 发表时间: 2022-11-22
• 期刊: JOURNAL OF EATING DISORDERS
• 影响因子: 4.1
• 作者: Bryant-Waugh, Rachel;Stern, Casey M.;Dreier, Melissa J.;Micali, Nadia;Cooke, Lucy J.;Kuhnle, Megan C.;Murray, Helen Burton;Wang, Shirley B.;Breithaupt, Lauren;Becker, Kendra R.;Misra, Madhusmita;Lawson, Elizabeth A.;Eddy, Kamryn T.;Thomas, Jennifer J.
• 通讯作者: Thomas, Jennifer J.

Lower Ghrelin Levels Are Associated With Higher Anxiety Symptoms in Adolescents and Young Adults With Avoidant/Restrictive Food Intake Disorder.

较低的生长素释放肽水平与患有回避/限制性食物摄入障碍的青少年和年轻人的较高焦虑症状相关。

• DOI: 10.4088/jcp.22m14482
• 发表时间: 2023
• 期刊: The Journal of clinical psychiatry
• 作者: ChovelSella,Aluma;Hadaway,Natalia;Stern,Casey;Becker,KendraR;Holsen,LauraM;Eddy,KamrynT;Micali,Nadia;Misra,Madhusmita;Thomas,JenniferJ;Lawson,ElizabethA
• 通讯作者: Lawson,ElizabethA

Disorders of gut-brain interaction common among outpatients with eating disorders including avoidant/restrictive food intake disorder.

• DOI: 10.1002/eat.23414
• 发表时间: 2021-06
• 期刊: INTERNATIONAL JOURNAL OF EATING DISORDERS
• 影响因子: 5.5
• 作者: Murray, Helen Burton;Kuo, Braden;Eddy, Kamryn T.;Breithaupt, Lauren;Becker, Kendra R.;Dreier, Melissa J.;Thomas, Jennifer J.;Staller, Kyle
• 通讯作者: Staller, Kyle