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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：
9237319
负责人：
Jamie Feusner
金额：
$ 41.7万
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/9237319
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 Chronic 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 Research Domain Criteria Resistance Rewards Risk Role Scanning Severities Shapes Signal Transduction Stimulus Subgroup Symptoms System Testing Time Translating Weight Weight Gain anxiety reduction anxious base behavior change behavioral outcome clinical predictors cortico-limbic circuits design early childhood high reward high risk imaging study improved individualized medicine mortality neural circuit neuroimaging neuroimaging marker novel outcome prediction predict clinical outcome premature public health relevance relapse risk relating to nervous system restoration standard care targeted treatment treatment strategy

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.