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

摘要/项目摘要 此应用程序寻求对阶段性项目的支持。在最初的(R61)两年阶段，我们将确定 认知补救疗法(CRT)可以增加厌食症父母和/或青少年的定势转移 神经性(AN)。我们的第二个目标是确定实现SET积极变化所需的适当剂量- 换档。达到我们的里程碑将触发对额外三年(R33)的支持，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 与单纯的FBT相比，治疗(FBT)将改善结果。定势转换(执行功能的一种 通常被称为认知灵活性)低效被假设为AN的一种内在表型， 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) 应激)在AN及其治疗期间，他们的认知灵活性显著降低。 虽然认知灵活性可以通过CRT提高，但我们对如何提高认知灵活性的了解存在显著差距 将CRT应用于青少年AN的治疗，特别是关于CRT的最合适靶点： 父母还是青少年？大多数关于青少年AN患者CRT的研究都是试验性和可行性的 研究和目标转移是针对青少年，而不是父母。我们假设，针对父母的可能不止是 对青少年的结果有很大影响。首先，我们必须确定是否可以通过CRT来增加SET移位。在最初 R61阶段我们建议招募并随机分配54个有AN孩子的家庭到FBT，FBT和 以家长为中心的CRT，或以青少年为中心的FBT。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。如果我们能实现我们的提议 里程碑在R61阶段，我们将继续进行R33阶段。有可能是一个(N=72个家庭)或两者都有 (n=93个家庭)CRT条件将在R33阶段检查。我们将确认我们在R61上的发现 阶段(靶点介入和CRT剂量)。我们还将检查青少年在FBT和FBT中的结果 FBT+(父母或青少年)CRT。结果包括体重增加率、AN的认知症状和 青少年常量营养素摄入量的多样性。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，以便通知结果。这一分阶段的R61/R33应用程序具有创新性 因为它是第一个只为父母改装CRT的公司。支持FBT+CRT增加移位的证据 父母/青少年将为未来的努力提供信息，以利用我们对儿童疾病(可遗传的)神经生物学的理解 青少年以改善结果。此外，如果父母的CRT显著改善了定势转移，我们就可以专注于 我们关于如何最好地加强目前的治疗，支持父母，并增加积极结果的努力 青春期，减少复发。即使是负面的结果也会影响我们对集合转换的理解 作为AN内表型的低效，它的测量，以及作为治疗靶点的有效性。

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.