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.

摘要 避免和限制性饮食在青少年心理健康障碍中很常见， 与生长不良、营养缺乏、精神症状和心理社会障碍有关。 新引入的DSM-5避免/限制性食物摄入障碍包括一些（但不是全部） 避免和限制性饮食介绍。初步证据表明，避免和限制性饮食是 高度异质性，以窒息或呕吐恐惧症为特征的摄入量差;对 进食;和/或极端的食物选择性。此外，很少有人知道它的病理生理学或长期- 长期成果。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、儿科学、内分泌学、生物统计学和功能性 神经影像学研究回避型和限制型饮食的风险机制和纵向结果。 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 按性别、年龄和坦纳分期进行匹配，以研究跨分析单元的RDoC结构 有助于避免和限制饮食。首先，我们假设负价（急性威胁/恐惧） 过度活跃（回路：在有效的恐惧范式期间杏仁核激活;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 恐惧症特征其次，我们假设唤醒/调节（稳态）功能障碍（回路： 在验证的食物范例期间的下丘脑和垂体后叶的低活化;激素：PYY、CKK、BDNF; 自我报告：饥饿和饱胀）将与低食欲特征相关。第三，我们将探索认知 系统（感知）过度敏感（回路：在品尝过程中初级味觉皮层的过度激活 范例;激素：PYY;自我报告：感觉特征;行为：味觉和嗅觉阈值，辨别， 生理学：味觉）及其与感官特征的相关性。我们预计 在这3种结构中，临床组群比对照组具有更大的功能障碍。然后我们将使用潜在的 类因素模型，以确定是否回避/限制性饮食包括多种不同的表型 (as先前的文献假设）或具有3个重叠维度的单一表型（如我们假设的）。我们 将跟踪我们的临床队列2年，以评估a）回避/限制性饮食的持续性，生长， 和精神病理学结果;和B）如果所有3个RDoC结构中的功能障碍预测结果。 本研究将在三个方面具有创新性和独特性：1）通过提供一个实证调查， 未充分研究的临床表现; 2）通过提供病理生理学和风险的首次调查 机制;和3）通过表征了解甚少的纵向结果。总之，概念化 在RDoC框架内的回避/限制性饮食，整合了思想，大脑和行为， 通过提供疾病分类学、治疗和预防信息，有可能减轻进食障碍的负担。

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.

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

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.

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