Attention Bias Modification for Anxiety: A Randomized Control Trial with Biomarke

描述(由申请人提供)：焦虑症是最常见的精神疾病诊断，多达29%的人在一生中受到影响。除了焦虑给个人造成的毁灭性代价外，每年给社会造成的经济损失估计约为466亿美元。选择性5-羟色胺再摄取抑制剂(SSRIs)和认知行为疗法(CBT)在治疗焦虑症方面取得了重大进展。然而，大规模使用它们的障碍和较高的缓解率(约50%)表明需要补充治疗方法。基于计算机的注意偏差修正(ABM)治疗简单、经济、易于管理，解决了常见的治疗障碍，并针对病理性焦虑的一个关键机制-威胁偏差，即对威胁刺激的夸大关注。ABM使用点探测任务的修改版本来训练焦虑的人将注意力从威胁中转移出来。最近的一项关于ABM对焦虑的影响的荟萃分析证明，ABM在降低焦虑症状严重程度方面的效果与CBT的效果相当。然而，还没有研究评估ABM对焦虑影响的特定神经认知机制，也没有试图确定可以预测治疗反应的生物标记物。拟议项目的目标是进行ABM治疗焦虑症的第一次大规模随机对照试验，其中整合了神经生物标记物的方法，以阐明潜在的治疗效果的神经认知机制，并测试这些生物标记物是否可以确定通过ABM治疗注意力障碍对哪些人最有效。头皮记录的事件相关电位由于其极高的时间分辨率和对ABM中涉及的自动和控制的注意过程的敏感性，将成为生物标记物。这项拟议的研究将追求两个具体目标：目标1将测试ABM治疗是否改变了90名焦虑成年人的ERP对威胁的反应。我们预测，接受ABM(与安慰剂相比)的成年人在训练后将表现出：(A)显著更大的ERPs，表明对威胁的注意加强了控制(N2/N2pc/P3)；以及(B)显著减少的ERPs，表明对威胁的促进注意减少(P1，P2)--尽管先前的混合证据表明，这些影响可能不如控制注意的效果那么强烈。我们将测试探索性假设，即由于ABM导致的这些事件相关电位的变化将预测基于反应时间的威胁偏差测量的减少。AIM 2将测试ABM引起的ERPS的变化(详见Aim 1)是否与焦虑严重程度的降低有关。我们预测，反映注意力控制增强的事件相关电位的变化，以及在较小程度上减少对威胁的注意促进，将预测焦虑的改善。 和治疗后的应激反应。我们将在治疗结束后四个月检查治疗效果的维持情况。我们还将通过测试一个探索性假设来评估ERPS是否可以用于预测治疗反应，该假设认为，在基线显示ERP反应表明对威胁有更大偏见的参与者(更大的促进作用(更大的P1/P2)和更少的注意力控制(减少的N2/N2PC/P3))将从注意力障碍的补救中受益最大，从而显示出ABM导致的焦虑严重程度和应激反应的最大降低。这项拟议的研究通过整合神经和行为标记物，代表着理解威胁偏见的可塑性和焦虑的补救机制的关键下一步。这些发现有可能产生关于焦虑症病因的高影响力知识，创造更有针对性、个性化和成本效益的焦虑症干预措施，并有助于预测治疗反应的个体差异。

DESCRIPTION (provided by applicant): Anxiety disorders are the most common psychiatric diagnosis, affecting as many as 29% of people during their lifetime. In addition to the devastating personal cost of anxiety, the yearly economic cost to society has been estimated to be around 46.6 billion. Major progress has been made in the treatment of anxiety using selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). However, obstacles to their wide-scale use and high remission rates (about 50%) suggest the need for complementary treatment approaches. Computer-based attention bias modification (ABM) treatment, which is brief, cost-effective, and easy to administer, addresses common treatment barriers and targets a key mechanism in pathological anxiety - the threat bias, or exaggerated attention towards threatening stimuli. ABM uses a modified version of the dot probe task to train anxious individuals to redirect attention away from threat. A recent meta-analysis of ABM effects on anxiety documents reductions in anxiety symptom severity, with effect sizes comparable to those for CBT. However, no research has evaluated specific neurocognitive mechanisms underlying ABM's effects on anxiety, nor attempted to identify biomarkers that can predict treatment response. The goal of the proposed project is to conduct the first large-scale RCT of ABM treatment for anxiety that integrates a neural biomarker approach to elucidate neurocognitive mechanisms underlying treatment efficacy and to test whether these biomarkers can identify those individuals for whom remediation of attention dysfunction via ABM will be most effective. Scalp-recorded event- related-potentials will be the biomarker due to their extremely high temporal resolution and sensitivity to automatic and controlled attentional processes that are implicated in ABM. The proposed research will pursue two Specific Aims: Aim 1 will test whether ABM treatment modifies ERP responses to threat in 90 anxious adults. We predict that adults who receive ABM (versus placebo) will exhibit at post-training: (a) significantly larger ERPs indicating increased control of attention to threat (N2/N2pc/P3); and (b) significantly reduced ERPs indicating diminished facilitated attention to threat (P1, P2) - although previous mixed evidence suggests these effects may be less robust than those for controlled attention. We will test the exploratory hypothesis that these changes in ERPs due to ABM will predict reductions in reaction-time based measures of threat bias. Aim 2 will test whether changes in ERPS due to ABM (detailed in Aim 1) are associated with reduced anxiety severity. We predict that changes in ERPs reflecting increased control of attention, and to a lesser degree reduced facilitation of attention to threat will predict amelioration of anxiety and stress reactivity following treatment. We will examine maintenance of treatment effects four months following treatment completion. We will also assess whether ERPS can be used to predict treatment response by testing the exploratory hypothesis that participants showing ERP responses at baseline indicating greater biased attention to threat (greater facilitation (larger P1/P2) and reduced control of attention (diminished N2/N2pc/P3)) will benefit most from remediation of attention dysfunction and thus show greatest reductions in anxiety severity and stress reactivity due to ABM. The proposed research, by integrating neural and behavioral markers, represents a crucial next step in understanding mechanisms underlying plasticity of the threat bias and remediation of anxiety. Such findings have the potential to yield high impact knowledge of the etiology of anxiety disorders, create more targeted, personalized, and cost-effective interventions for anxiety, and help predict individual differences in treatment response.