Emotion Regulation in Anxiety & Depression: A Novel Neurobehavioral Intervention

描述(由申请人提供)：焦虑和情绪障碍非常普遍，通常是并存的，当这样的时候，与增加的发病率和残疾有关。特别是，抑郁症背景下的焦虑预示着一系列治疗方法的更糟糕的结果。焦虑和情绪障碍中过度的、无法控制的负面情绪的共性表明，情绪反应和调节方面存在核心缺陷。我们和其他人描绘了一个神经行为系统，涉及前扣带回、杏仁核和外侧前额叶皮质，参与情绪反应和调节。在患有焦虑和情绪障碍的患者中，这一回路内的活动和连接都受到干扰，支持了情绪处理功能障碍是这些障碍的核心的假设，并且现在有经过验证的工具可用于客观评估这一神经系统。这些发现为旨在改善情绪调节的新型干预方法奠定了坚实的科学基础，这些方法可以通过互联网提供，从而也增加了有效治疗的可获得性。我们计划试行一部小说，互联网 提供基于神经可塑性的神经行为干预，通过1)灌输对积极刺激的偏见，2)改善对情绪分心的抵抗，以及3)更全面地增强执行功能(例如，工作记忆、任务切换、抵抗干扰)，从而改善情绪调节，因为这些都是成功实施情绪调节(ER)所必需的。在R21阶段，30名无药物治疗的焦虑性抑郁症患者(总分为Ham-D17e16，Ham-D17焦虑量表)将接受为期60天的互联网培训。这一阶段的目标是优化培训和评估程序(症状、行为和功能磁共振成像)，并为培训推广到与焦虑和抑郁有关的措施提供初步证据。在R33阶段，60名无药物治疗的焦虑性抑郁症患者将被随机分配到接受为期60天的ER神经行为干预(如果R21表明有调整)或在线任务的主动控制臂，这些在线任务同样吸引人，但没有提供情绪调节好处。这一阶段的目的是提供初步证据，支持神经行为干预的优化版本的效用，重点是大规模临床试验的效果大小估计和招募和实施参数的描述。我们预计，我们针对急诊室的互联网传递的适应性神经行为培训将适用于一系列精神障碍，特别是情绪或焦虑症。这项拟议研究的成功完成将为这种新的干预方法的实用性提供令人信服的初步证据，该方法以对焦虑和抑郁核心缺陷的神经科学理解为指导，用于更大规模和更明确的临床试验。 公共卫生相关性：焦虑和情绪障碍非常普遍，通常是并存的，当出现这种情况时，与发病率和残疾增加相关，以及一系列治疗的较差结果。心理社会治疗，即使是有效的，患者往往很难获得--因此，迫切需要开发新的 治疗干预。这项拟议工作的长期目标是利用我们对焦虑和抑郁的神经科学新理解，将其转化为一种高度创新的、基于大脑的神经行为疗法，该疗法可以补充或形成目前有限的治疗方案的替代方案。

DESCRIPTION (provided by applicant): Anxiety and mood disorders are highly prevalent, often co-morbid, and when so, are associated with increased morbidity and disability. In particular, anxiety in the context of depression predicts worse outcome with a range of treatments. The commonality of excessive, uncontrollable negative emotion across anxiety and mood disorders suggests a core deficit in emotional reactivity and regulation. We, and others, have delineated a neurobehavioral system, involving the anterior cingulate, amygdala, and lateral prefrontal cortex, that is involved in emotional reactivity and regulation. Both activity ad connectivity within this circuit are perturbed in patients with anxiety and mood disorders, supporting the hypothesis that dysfunction in the handling of emotion lies at the core of these disorders, and that validated tools are now available for objectively assessing this neural system. These findings constitute a robust scientific foundation for novel intervention approaches aimed at improving emotion regulation, which could be delivered over the internet, thereby also increasing availability of effective treatments. We propose to pilot a novel, internet delivered neuroplasticity-based neurobehavioral intervention, which improves emotion regulation by 1) instilling a bias towards positive stimuli, 2) improving resistance to emotional distraction, and 3) enhancing executive functioning more generally (e.g. working memory, task switching, resisting interference), as these are required for successful implementation of emotion regulation (ER). In the R21 phase, thirty medication-free patients with anxious depression (total Ham-D1¿7e16, Ham-D17 anxiety subscale ¿7) will be given 60 days of internet-delivered training. The aim of this phase is to optimize the training and assessment procedures (symptom, behavioral and fMRI), as well as to provide initial evidence for generalization of the training to measures relevant for anxiety and depression. In the R33 phase, sixty medication-free patients with anxious depression will be randomized to receive the 60-day ER neurobehavioral intervention (with adjustments if indicated by the R21) or an active control arm of online tasks that are similarly engaging but provide no emotion regulatory benefits. The aim of this phase is to provide initial evidence supporting the utility of an optimizd version of the neurobehavioral intervention, focusing on effect size estimation and delineation of recruitment and implementation parameters for a large-scale clinical trial. We foresee our internet-delivered, adaptive neurobehavioral training for ER as being applicable for a range of psychiatric disorders, and in particular for mood or anxiety disorders. Successful completion of the proposed study would provide compelling initial evidence for the utility of this novel intervention approach, guided by a neuroscientific understanding of core deficits in anxiety and depression, for a larger and more definitive clinical trial. PUBLIC HEALTH RELEVANCE: Anxiety and mood disorders are highly prevalent, often co-morbid, and when so, are associated with increased morbidity and disability, as well as worse outcome with a range of treatments. Psychosocial treatments, even when effective, are often difficult for patients to obtain - thus, there is a pressing clinical need for development of novel treatment interventions. The long-term objective of the proposed work is to leverage our emerging neuroscientific understanding of anxiety and depression into a highly innovative, novel brain-based neurobehavioral treatment that can augment or form an alternative to the currently limited set of treatments.