Anxiety and reward interaction and prediction of outcomes in anorexia nervosa

 描述（由申请人提供）：本研究的目的是了解焦虑对神经性厌食症（AN）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。AN因其对干预的抵抗和所有精神疾病中最高的死亡率而臭名昭著。各种形式的强化治疗可能会成功地恢复体重，但治疗的总体益处仍然有限，早期复发率异常高。虽然有证据表明遗传因素在易感性中起作用，但对AN的机械神经回路知之甚少。AN患者通常在饮食紊乱之前的生命早期表现出前驱焦虑。这种表型表达可能表现为夸大的威胁感知，以及对重量和形状变化信号的超敏反应和回避。与此同时，限制型AN的个体，从幼儿期开始，对接触新的和高回报的环境保持沉默。这与大多数心理测量学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。然而，焦虑和奖励回路之间的相互作用从未在AN中被询问过。有大量的证据表明，不同但重叠的神经系统介导的方法（与奖励）和回避（与焦虑），这是整合在平衡和切换之间的行为有关的主要价态。因此，我们认为，高度的反应性皮质边缘电路潜在的焦虑 可能导致对奖励刺激的反应能力减弱。这可能在临床上转化为参与治疗的动机较低;实际上，基于对未来结果益处的预期，改变改善所需的行为和思维模式的动力较低，导致体重减轻和症状恶化的过程轨迹。因此，本研究调查了最近完成强化治疗的AN患者的这种焦虑和奖励相互作用，并将随访6个月以上的症状复发程度。42名限制型AN青少年和42名匹配的对照将参与奖励任务，其中个体定制的焦虑激发单词刺激交错，同时进行功能性磁共振成像（fMRI）。将分析奖励和焦虑神经回路活动及其相互作用与其预测随后6个月内BMI和症状严重程度变化的能力的关系。因此，使用新颖的设计来询问正和负效价回路的功能可能导致识别与疾病持续性相关的维度表型，这是为高危亚组开发个性化和有针对性的治疗策略（例如减少刺激特异性焦虑和/或增强积极影响）的关键一步。

 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.