Neurobehavioral metrics for the assessment and treatment of depression

描述(申请人提供)：为了推进抑郁症的多维评估和治疗，本方案的广泛创新有三个方面。首先，我们将使用功能磁共振成像(FMRI)和大样本的受试者内设计来确定抑郁症患者的情绪、社会功能和奖励反应的神经行为指标。其次，我们将评估认知行为治疗后这些指标的变化，并评估这些指标对预测特定领域治疗结果的有效性。第三，我们将使用这些方法来开发基于情绪衍生大脑状态的功能磁共振引导的神经反馈，并测试神经反馈引发情绪改善的能力。该项目的首要目标是确定可用作评估和治疗严重抑郁障碍的多维指标的量化神经行为内表型。随之而来的假设是，严重抑郁症患者的快感缺失、社交障碍和消极情绪可能分别映射到基于奖励、社交功能和情绪的任务中诱发的神经活动。我们认为，这些措施可以用来定制个人的治疗方案，并开发新的个性化神经行为疗法来治疗抑郁症。具体目标如下：目标1：识别和改进严重抑郁障碍患者的快感缺失、社会功能和负面情绪的神经行为测量。我们将使用三种不同的任务和功能磁共振成像来量化情绪刺激、奖励和社会功能的神经行为反应，这是在抑郁症患者的受试者内部设计中的。我们将测试这一假设，即可以根据这三个领域的异常情况的量化神经行为谱来衡量严重抑郁症的各个方面。目的2：确定认知行为疗法治疗反应的特定领域变化和预测因素。我们将在经验性认知行为疗法(CBASP)治疗12周前和12周后对患有严重抑郁症的患者进行扫描，以确定a)治疗反应的特定领域神经行为预测因素，以及b)CBASP引发的症状变化的神经行为伴随因素。这个目标将检验这样一个假设，即目标1中确定的奖励、社交功能和基于情绪的神经反应将为特定领域的变化提供不同的预测效用。目的3：评估受试者调节从情绪状态形成的神经反馈界面的能力，并评估神经反馈后的情绪变化。在积极或消极的情绪激发过程中，受试者将从神经反应中获得神经反馈。这一目标将检验这样的假设：a)个人可以学习分别调节与积极情绪和负面情绪相关的大脑分布模式，以及b)通过神经反馈，抑郁的人将实现情绪改善。 与公共卫生相关：目前针对严重抑郁症的药物和心理治疗努力只是中等有效，对那些对特定治疗方案表现出阳性反应的人的个体特征知之甚少。抑郁症的人力和财政成本促使人们尝试确定可用于(A)改进抑郁症的评估和治疗以及(B)开发治疗抑郁症的新疗法的多维量化神经行为衡量标准。

DESCRIPTION (provided by applicant): To advance the multi-dimensional assessment and treatment of major depression, the broad innovations of this proposal are threefold. First, we will use functional magnetic resonance imaging (fMRI), and a within-subjects design with large sample sizes to identify neurobehavioral measures of mood, social functioning, and reward response in depression. Second, we will evaluate changes in these measures following cognitive behavioral therapy and assess the utility of these measures for predicting domain-specific treatment outcomes. Third, we will use these measures to develop fMRI-guided neurofeedback based on mood-derived brain states and test the capacity of the neurofeedback to elicit mood improvement. The overarching goal of this project is to identify quantitative neurobehavioral endophenotypes that may be used as multi-dimensional metrics in the assessment and treatment of major depressive disorder. The accompanying hypothesis is that anhedonia, social impairment, and negative mood in major depression may be mapped onto neural activity evoked during reward-, social functioning-, and emotion-based tasks, respectively. We believe that these measures may be used both to tailor individuals' treatment regimens and to develop novel personalized neurobehavioral therapies for depression. The specific aims are below: Aim 1: Identify and refine neurobehavioral measures of anhedonia, social functioning, and negative mood in individuals with major depressive disorder. We will use three distinct tasks and fMRI to quantify neurobehavioral responses to emotional stimuli, reward, and social functioning, in a within-subjects design in individuals with depression. We will test the hypothesis that aspects of major depression may be measured on a quantitative neurobehavioral spectrum of anomalies in these three domains. Aim 2: Identify domain-specific changes and predictors of treatment response to cognitive behavioral therapy. We will scan individuals with major depressive disorder before and after 12 weeks of empirically-supported cognitive behavioral therapy (CBASP) to identify a) domain-specific neurobehavioral predictors of treatment response and b) neurobehavioral concomitants of symptom changes elicited with CBASP. This Aim will test the hypothesis that the reward-, social-functioning, and mood- based neural responses identified in Aim 1 will serve differential predictive utility for domain-specific changes. Aim 3: Assess subjects' ability to modulate a neurofeedback interface developed from mood states and evaluate mood changes following neurofeedback. Subjects will receive neurofeedback derived from neural responses during positive or negative mood provocation. This aim will test the hypotheses that a) individuals can learn to modulate distributed brain patterns associated with positive and negative emotion, respectively, and that b) through neurofeedback, depressed individuals will achieve mood improvements. PUBLIC HEALTH RELEVANCE: Current pharmaceutical and psychotherapeutic efforts for major depression are only moderately efficacious, and little is known about the individual characteristics of those who exhibit a positive response to specific treatment regimens. The human and fiscal cost of depression motivates the attempt to identify multi- dimensional quantitative neurobehavioral measures that may be used to (a) refine the assessment and treatment of depression and (b) develop novel therapies for depression.