Shifting Perspectives: Enhancing outcomes in adolescent anorexia nervosa with cognitive remediation therapy

摘要/项目总结 本申请寻求对分阶段项目的支持。在初始（R61）2年阶段，我们将确定 认知矫正疗法（CRT）可以增加厌食症患者的父母和/或青少年的定势转换 Nervosa（AN）.我们的第二个目标是确定实现集的积极变化所需的适当剂量- 转移达到我们的里程碑将触发额外三年的支持（R33），以确认目标 参与和适当的剂量。我们还将评估是否将CRT添加到基于家庭的 与单独FBT相比，治疗（FBT）将改善结局。定势转换（一种执行功能 通常称为认知灵活性）的低效率被假设为AN的内表型， 因此是可遗传的认知灵活性可能会受到营养不良等情境因素的负面影响， 压力和焦虑很可能青少年（营养不良）和父母（营养不良） 压力）在AN及其治疗期间经历了基于状态的认知灵活性的显著降低。 虽然认知灵活性可以通过CRT增加，但我们对如何增加认知灵活性的认识存在重大差距。 将CRT应用于青少年AN的治疗，特别是关于CRT的最合适靶点： 父母或青少年？目前对青少年AN患者CRT的研究大多数是初步的和可行的 研究和青少年的目标设定转移，而不是父母。我们假设，针对父母可能更 对青少年的影响。首先，我们必须确定我们是否可以通过CRT来增加集合移位。在初始 R61阶段，我们建议招募并随机分配54个有AN儿童的家庭进行FBT，FBT与 父母聚焦CRT，或FBT与双聚焦CRT。目标参与度将通过神经- 认知和行为灵活性的心理评估和自我报告。如果我们满足我们的提议 在R61阶段的里程碑之后，我们将进入R33阶段。可能有一个（N = 72个家庭）或两个 （N = 93个家庭）将在R33阶段检查CRT条件。我们将从R61上确认我们的发现 阶段（靶点接合和CRT剂量）。我们还将研究青少年单独FBT与 FBT+（父母或青少年）CRT。结果包括体重增加率，AN的认知症状， 青少年大量营养素摄入的多样性。我们将收集关于假定主持人的初步数据 和/或两个阶段的调解人，以便告知结果。这种分阶段R61/R33应用具有创新性 因为它是第一个将CRT仅适用于父母的。证据支持FBT+CRT增加 父母/青少年将告知未来的努力，以利用我们对AN（遗传）神经生物学的理解， 青少年改善结果。此外，如果父母的CRT显著改善了设置转换，我们可以专注于 我们的努力，如何最好地加强目前的治疗，支持父母，并增加积极的结果， 青春期和减少复发。即使是负面的结果也会告诉我们如何理解定势转换 作为AN中的内表型的无效性、其测量以及作为治疗靶点的有用性。

ABSTRACT/PROJECT SUMMARY This application seeks support for a phased project. In the initial (R61) 2-year phase we will establish that Cognitive Remediation Therapy (CRT) can increase set-shifting in parents of and/or adolescents with Anorexia Nervosa (AN). Our second aim is to determine the appropriate dose needed to achieve positive change in set- shifting. Attaining our milestone would trigger support for three additional years (R33) to confirm target engagement and appropriate dose. We will also evaluate whether or not adding CRT to Family Based Treatment (FBT) will improve outcome compared to FBT alone. Set-shifting (a type of executive functioning often referred to as cognitive flexibility) inefficiencies are hypothesized to be an endophenotype of AN and are, therefore, heritable. Cognitive flexibility can be impacted negatively by situational factors such as malnutrition, stress, and anxiety. It is likely that both adolescents (who are malnourished) and parents (who are under stress) experience significant state-based reduction in their cognitive flexibility during AN and its treatment. While cognitive flexibility can be increased through CRT, there is a significant gap in our knowledge about how to apply CRT to the treatment of adolescent AN, specifically concerning the most appropriate target for CRT: parents or adolescents? The majority of research on CRT with adolescents with AN are pilot and feasibility studies and target set-shifting in adolescents, not parents. We hypothesize that targeting parents may be more impactful for adolescent outcome. First, we must determine if we can increase set-shifting via CRT. In the initial R61 phase we propose to recruit and randomly assign 54 families who have a child with AN to FBT, FBT with parent-focused CRT, or FBT with adolescent-focused CRT. Target engagement will be assessed via neuro- psychological assessment and self-report of cognitive and behavioral flexibility. If we meet our proposed milestones in the R61 phase, we will proceed to the R33 phase. It is possible that one (N = 72 families) or both (N = 93 families) CRT conditions will be examined in the R33 phase. We will confirm our findings from the R61 phase (target engagement and dose of CRT). We will also examine adolescent outcome in FBT alone versus FBT+(parent or adolescent) CRT. Outcome includes rate of weight gain, cognitive symptoms of AN, and variety in macronutrient intake by the adolescent. We will gather preliminary data on putative moderators and/or mediators across both phases in order to inform results. This phased R61/R33 application is innovative in that it is the first to adapt CRT to parents only. Evidence supporting FBT+CRT to increase set-shifting in parents/adolescents will inform future efforts to leverage our understanding of (heritable) neurobiology of AN in adolescents to improve outcome. Further, if CRT for parents significantly improves set-shifting, we can focus our efforts on how best to augment current treatments, support parents, and increase positive outcomes for the adolescent and reduce relapse. Even negative results would inform our understanding of set-shifting inefficiencies as an endophenotype in AN, its measurement, and usefulness as a target in treatment.