Reducing Rumination in Depression: Mechanisms and Effects

 描述(由申请人提供)：严重抑郁障碍(MDD)是所有精神疾病中最普遍和最具破坏性的疾病之一，也是世界上最沉重的疾病。因此，我们当务之急是确定和审查改变维持千年发展目标所涉及的机制的影响。在此背景下，研究人员已经证明，难以从工作记忆中删除负面信息是MDD的核心认知特征。重要的是，这种认知困难与抑郁症状和沉思的持续有关，这种思维方式阻碍了从压力中恢复，并加剧了负面情绪。到目前为止，将难以从工作记忆中去除负面信息与沉思、负面情绪的持续性以及MDD的压力恢复联系起来的研究一直受到相关方法的限制。重要的是，认知偏差修正(CBM)文献强调了操纵认知过程的可行性，这既是为了测试因果关系，也是为了确定参与疾病发生和维持的机制。因此，这项研究的一个主要目的是建立在已建立的CBM方法的基础上，以提高抑郁个体从工作记忆中消除负面信息(RNI)的能力。我们建议检查RNI训练的认知、情感和生物效应(目标1)。此外，我们还建议研究RNI训练有益效果的神经机制(目标2)。为了实现这些目标，50名被诊断为MDD的参与者将被分配接受真实或虚假的RNI培训。所有参与者将完成培训前的实验室和神经成像课程，六次真实或虚假的家庭RNI培训课程，培训后的实验室和神经成像课程，以及为期三个月的后续评估。我们预计，与Sham RNI培训相比，Real RNI培训将a)提高抑郁参与者从培训前到培训后从工作记忆中删除负面信息的能力；b)减少沉思和抑郁症状；以及c)改善随后的情绪和生物压力恢复。我们进一步预期，RNI训练将通过减少训练前和训练后对认知努力不利的区域(背侧前扣带回、顶叶后叶和岛叶皮质)的大脑激活，以及通过减少潜在冥想区域(亚膝前扣带回皮质和内侧前额叶皮质)的功能连接来实现其有益的效果。本研究的结果将加深我们对工作记忆中的偏见、沉思和抑郁症状之间的关系的理解，并将有助于识别和阐明导致MDD发生和维持的具体机制。

 DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is among the most prevalent and devastating of all psychiatric disorders, and is the single most burdensome disease worldwide. Consequently, it is imperative that we identify and examine the effects of altering mechanisms involved in the maintenance of MDD. In this context, investigators have documented that difficulty removing negative information from working memory is a core cognitive feature of MDD. Importantly, this cognitive difficulty is implicated in the persistence o both depressive symptoms and rumination, a style of thinking that hinders recovery from stress and exacerbates negative affect. To date, research linking difficulty removing negative information from working memory with rumination, the persistence of negative affect, and stress recovery in MDD has been limited by the use of correlational methodologies. Importantly, the Cognitive Bias Modification (CBM) literature underscores the viability of manipulating cognitive processes both to test causal relations and to identify mechanisms involved in the onset and maintenance of disorders. Therefore, a major aim of the proposed study is to build on established CBM methods to improve depressed individuals' ability to remove negative information (RNI) from working memory. We propose to examine the cognitive, affective, and biological effects of RNI training (Aim 1). In addition, we also propose to examine the neural mechanisms that underlie the beneficial effects of RNI training (Aim 2). To achieve these aims, 50 participants diagnosed with MDD will be assigned to receive either Real or Sham RNI training. All participants will complete pre-training laboratory-based and neuroimaging sessions, six at-home Real or Sham RNI training sessions, post-training laboratory-based and neuroimaging sessions, and a three-month follow-up assessment. We expect that, compared to Sham RNI training, Real RNI training will a) improve depressed participants' ability to remove negative information from working memory from pre- to post-training; b) decrease levels of rumination and depressive symptoms; and c) improve subsequent emotional and biological stress recovery. We further expect that RNI training will achieve its beneficial effects by decreasing brain activation from pre- to post-training in regions that subserve cognitive effort (dorsal anterior cingulate, posterior parietal lobe, and insular cortex), and by decreasing functional connectivity in regions posited to underlie rumination (subgenual anterior cingulate cortex and medial prefrontal cortex). The results of this study will increase our understanding of the relations among biases in working memory, rumination, and depressive symptoms, and will help to identify and elucidate specific mechanisms that contribute to the onset and maintenance of MDD.