Anxiety and reward interaction and prediction of outcomes in anorexia nervosa

焦虑和奖赏相互作用以及神经性厌食症结果的预测

基本信息

批准号：
8965487
负责人：
Jamie Feusner
金额：
$ 43.94万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-05 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8965487
关键词：
Acute Adolescent Affect Aftercare Anorexia Nervosa Anti-Anxiety Agents Anxiety Appearance Behavior Behavioral Behavioral inhibition Body Size Body Weight decreased Brain Cessation of life Clinical Cognitive Corpus striatum structure Development Dimensions Discipline Disease Early treatment Eating Eating Disorders Emotional Environment Equilibrium Evaluation Exhibits Expectancy Exposure to Feedback Food Foundations Functional Magnetic Resonance Imaging Future Genetic Hypersensitivity Individual Intervention Knowledge Lead Life Light Mediating Mental disorders Motivation Negative Valence Outcome Outpatients Participant Pattern Perception Persons Phenotype Play Positive Valence Predisposition Psychometrics Psychopathology Relapse Relative (related person)Research Domain Criteria Resistance Rewards Risk Role Scanning Severities Shapes Signal Transduction Staging Stimulus Subgroup Symptoms System Testing Time Translating Weight Weight Gain anxiety reduction anxious base behavior change behavioral outcome cortico-limbic circuits design early childhood high reward high risk improved individualized medicine mortality neural circuit neuroimaging novel premature public health relevance relating to nervous system restoration standard care targeted treatment

项目摘要

DESCRIPTION (provided by applicant): The purpose of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts clinical outcome subsequent to intensive treatment. AN is notorious for its resistance to interventions and for the highest mortality rate of all psychiatric disorders. Variou forms of intensive treatment may succeed in restoring weight, yet overall benefits of treatment remain limited and early relapse is unusually high. While evidence suggests that genetic factors play a role in susceptibility, remarkably little is known about AN's mechanistic neural circuitry. Individuals with AN typically exhibit prodromal anxiety early in life prior to disordered eating. This phenotypic expression may manifest as exaggerated threat perception, and hypersensitivity to and avoidance of signals of weight and shape change. In parallel, individuals with restricting-type AN, beginning in early childhood, are reticent to exposure to novel and high reward environments. This is in line with most psychometric and neuroimaging studies that suggest low responsiveness to natural rewards, as well as aberrant reward system activity and dopaminergic function. However, the interaction between anxiety and reward circuits has never been interrogated in AN. There is substantial evidence of distinct yet overlapping neural systems mediating approach (related to reward) and avoidance (related to anxiety), which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus, we posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute to diminished capacity to respond to reward stimuli. This may translate clinically to lower motivation to engage in treatment; in effect, a lower drive to change behaviors and thought patterns necessary for improvement based on expectancy of benefits of future outcome, resulting in a course trajectory of weight loss and worsening of symptoms. Accordingly, this study investigates this anxiety and reward interaction in individuals with AN who have recently completed intensive treatment, and whom will be followed for degree of symptom relapse over 6 months. Forty two adolescents with restricting-type AN and 42 matched controls will engage in reward tasks in which individually- tailored anxiety provoking word stimuli are interleaved, while undergoing functional magnetic resonance imaging (fMRI). Reward and anxiety neural circuit activity, and their interaction, will be analyzed in relationship to their ability to predict trajetory of BMI and symptom severity changes over the subsequent 6 months. Using novel designs for interrogating the functionality of positive and negative valence circuits may thus lead to identification of dimensional phenotypes associated with disease persistence, a critical step towards developing individualized and targeted treatment strategies (such as reduction of stimuli-specific anxiety and/or enhancement of positive affect) for high-risk subgroups.

描述（由适用提供）：本研究的目的是了解焦虑对厌食症神经（AN）的青少年奖励反应的影响，以及这种相互作用如何预测强化治疗后的临床结果。一个人因抵抗干预措施和所有精神疾病的死亡率最高而臭名昭著。 variou的强化治疗形式可能会成功恢复体重，但治疗的总体益处仍然有限，早期救济异常高。尽管有证据表明遗传因素在易感性中起作用，但对AN的机械神经元回路知之甚少。在饮食失调之前，通常在生命的早期就患有裸露的前驱焦虑症。这种表型表达可能表现为夸张的威胁感知，对体重和形状变化的信号的过敏和避免。同时，从童年开始，具有限制型AN的个体是对新颖和高奖励环境的沉默寡言。这与大多数心理测量和神经影像学研究一致，这些研究表明对自然奖励的反应性低，以及异常的奖励系统活动和多巴胺能功能。但是，焦虑与奖励电路之间的相互作用从未在AN中受到审问。有大量证据表明，不同但重叠的神经系统介导方法（与奖励有关）和回避（与动画有关），它们整合到与主要价值状态相关的行为之间的平衡和切换中。这是我们提倡的，是动画基础电路的高度反应性可能有助于减少响应奖励刺激的能力。这可能会在临床上转化为降低接受治疗的动力。实际上，根据对未来结果的收益的期望，改变行为和思维模式的动力较低，从而导致体重减轻和症状担心的课程轨迹。根据该研究的研究，该研究调查了最近已经完成强化治疗的人的这种焦虑和奖励相互作用，并且将在6个月内遵循症状继电器的程度。有42个具有限制型AN和42个匹配的控件的青少年将参与奖励任务，在这些任务中，单独量身定制的动画引起了单词刺激，同时进行了功能性磁共振成像（fMRI）。奖励和动画神经电路活动及其相互作用将与他们预测BMI造成影响的能力和随后6个月内症状严重程度变化的关系进行分析。因此，使用新颖的设计来询问正价电路和负价电路的功能，可能会导致鉴定与疾病持久性相关的维度表型，这是发展个性化和有针对性的治疗策略（例如减少刺激特异性动画和/或增强阳性影响的刺激）的关键步骤）。