A Randomized Controlled Trial of PCIT-ED For Preschool Depression

描述（由申请人提供）：本提议的竞争性补充/修订扩展了正在进行的亲子互动治疗情绪发展（pct - ed）随机对照试验的目标，增加了治疗直接针对的三个核心情绪领域的补充神经测量。这包括通过奖励处理来衡量的快乐基调，以及通过对失去/缺乏奖励的反应和情绪调节来衡量的消极情绪反应。pct - ed是一种针对学龄前抑郁症的早期心理治疗干预，直接针对情绪反应性、快乐基调和情绪调节。在正在进行的随机对照试验中，这些情绪域是通过行为来测量的，但这一补充将允许对这些结构的神经相关性进行独特的研究。治疗的目的是针对这些情绪发展的新组成部分，已知在学龄前抑郁症中被改变，通过在这段相对较大的神经可塑性和快速发展变化时期的亲子关系来发挥作用。研究领域标准（RDoC）提供了一个框架来识别和测试核心行为和神经维度，这些维度有助于改变与早发性抑郁症相关的享乐加工和情绪反应和调节。在青少年和成年人中，抑郁症与奖励反应能力下降和损失反应能力增强有关。我们建议对抑郁症学龄前儿童（PO-MDD）在治疗前、治疗中和治疗后进行研究，使用经过验证的ERP和fMRI标记物对奖励和损失的反应，这些标记物之前用于表征这些领域的抑郁相关变化。我们将测试以下假设，即pct - ed会改善对奖励和损失的反应性的行为和神经指标，并且这些神经指标将预测谁最有可能做出反应。这些数据可以为治疗疗效的翻译生物标志物和治疗反应的预测因子提供关键证据，在早期神经可塑性发育时期尤其重要。拟议的补充将通过使用适合年龄的范例，测量治疗前和治疗后/等待条件，增加ERP和fMRI测量这些特定结构，以告知治疗反应的预测者和潜在的变化机制。这项附加研究与NIMH战略计划和RDoC倡议一致，通过调查抑郁症的核心大脑行为关系，并在发展的早期针对它们。据我们所知，正在进行的R01是第一个大规模的抑郁症早期干预的RCT，因此从行为和神经的角度研究幼儿情感系统的变化提供了前所未有的机会。我们将ERP和fMRI纳入其中，以确定这些互补措施是否识别神经相关物/变化机制和/或治疗反应预测因子中的独特或重叠方差。

DESCRIPTION (provided by applicant): This proposed competitive supplement/revision extends the aims of this ongoing randomized controlled trial of Parent Child Interaction Therapy Emotion Development (PCIT-ED) by adding complimentary neural measures of three core emotion domains that are directly targeted by the treatment. This includes hedonic tone measured by reward processing and negative emotion reactivity measured by response to loss/lack of reward as well as emotion regulation. PCIT-ED is an early psychotherapeutic intervention for preschool depression that directly targets emotion reactivity, hedonic tone and emotion regulation. These emotion domains are measured behaviorally in the ongoing RCT, but this supplement will allow a unique investigation of the neural correlates of these constructs. The treatment is designed to target these emerging components of emotion development, known to be altered in preschool depression, by acting through the parent child relationship during this period of relatively greater neuroplasticity and rapid developmental change. The Research Domain Criteria (RDoC) provides a framework in which to identify and test core behavioral and neural dimensions contributing to altered hedonic processing and emotion reactivity and regulation associated with early onset depression. Depression is associated with both decreased responsiveness to reward and enhanced responsiveness to loss in adolescents and adults. We propose to study depressed preschoolers (PO-MDD) prior to treatment, mid-treatment and post-treatment using well-validated ERP and fMRI markers of response to reward and loss previously used to characterize depression related alterations in these domains. We will test the hypotheses that behavioral and neural indicators of responsiveness to reward and loss will improve as a result of PCIT-ED, and that these neural measures will predict who is most likely to respond. Such data could provide crucial evidence of translational biomarkers of treatment efficacy and predictors of treatment response, of particular importance during this early neuroplastic developmental period. The proposed supplement will add ERP and fMRI measures of these specific constructs through the use of age appropriate paradigms, measured pre and post treatment/wait condition, to inform predictors of treatment response and potentially mechanisms of change. This add-on study is in line with the NIMH strategic plan and the RDoC initiative by investigating brain behavior relationships central to depression and targeting them early in development. The ongoing R01 is the first large scale RCT of an early intervention for depression to our knowledge and therefore provides an unprecedented opportunity to investigate changes in affective systems in very young children from both behavioral and neural perspectives. We include both ERP and fMRI to determine whether these complementary measures identify unique or overlapping variance in the neural correlates/mechanisms of change and/or the predictors of treatment response.