Defining biotypes of PTSD with resting-state connectivity

创伤后应激障碍不是一种单一的障碍，而是一种不同的综合症，两者都有 症状学和对治疗的反应。尽管我们在这方面取得了重大突破 了解与创伤后应激障碍相关的神经生物学途径，其神经生物学异质性 阻碍了一致的生物标志物的识别，而这些生物标志物仍然难以捉摸。以前工作的一个主要局限性 创伤后应激障碍的临床症状和行为亚型没有充分捕捉到 潜在的神经生物学，因为相同的症状可能源于不同的潜在神经生物学 机械装置。为了解决这一关键差距，拟议的研究将开创一种新的分析方法，以 根据共享的大脑模式确定创伤后应激障碍的神经生理亚型或生物型 静息功能磁共振连接功能障碍。以下内容旨在发现和验证基于MRI的 退伍军人创伤后应激障碍的生物型具有广泛的未来应用前景，如改善客观诊断 工具，为干预提供目标，并预测谁将对特定治疗做出反应。 设计和方法：目前的方案将使用多部位神经、临床和认知数据来 发现基于静息功能磁共振成像的创伤后应激障碍的生物型，确定其可靠性和可重复性，以及与 症状、合并症和认知。退伍军人的影像和临床数据将主要来自退伍军人管理局 波士顿(n&gt；500)以及休斯顿退伍军人管理局(n&gt；200)的复制站点。另外300名参与者将是 被招募到最先进的认知电池中，以确定这些生物类型是否具有认知特征 可以从敏感的认知测试中推断出来。分析方面，这项研究将使用一套通用的技术， 一个令人兴奋的脑成像新时代的前沿--基于磁共振成像的“指纹”，或测量和建模 基于功能磁共振成像的连接体(功能性)中的可重复性和但实质性的个体差异 连接性)。 目标。目标1.使用现有数据(n&gt；500)，我们将A)定义不同的创伤后应激障碍的生物类型 功能磁共振成像连接的模式。我们将进一步测试这些生物型在两个连续的 静息扫描，以及预测单个退伍军人的创伤后应激障碍生物型的能力。我们还将探索是否确定 症状和合并症与创伤后应激障碍的生物型不同。目标2.我们将确定横跨- 通过1-2年后对相同参与者的重复评估来检验这些生物型的时间可靠性 (N&gt；300)。目标3.我们将在来自休斯顿退伍军人管理局的独立复制数据集中验证这些生物类型 (N&gT；200名退伍军人)。目标4.我们将收集一个全面的最先进的认知电池(n=300) 测量创伤后应激障碍的特定机制(例如，恐惧学习、抑制控制、注意偏向)以确定是否 这些生物类型可以从认知表现特征中推断出来。

Posttraumatic stress disorder is not a unitary disorder, but rather a heterogeneous syndrome, both in its symptomatology and response to treatment. Although there have been important breakthroughs in our understanding of neurobiological pathways associated with PTSD, its neurobiological heterogeneity has impeded the identification of consistent biomarkers, which remain elusive. A major limitation of previous work is that clinical symptoms and behavioral subtypes of PTSD do not adequately capture variation in the underlying neurobiology, as the same symptoms can stem from different underlying neurobiological mechanisms. To address this critical gap, the proposed study will pioneer a new analytic methodology to identify neurophysiological subtypes, or biotypes of PTSD, based on shared patterns of brain dysfunction in resting fMRI connectivity. The following aims to discover and validate MRI-based biotypes of PTSD in our Veterans have wide-ranging future applications such as improving objective diagnostic tools, providing targets for interventions, and predicting who will response to a particular treatment. DESIGN AND METHODS: The current proposal will use multi-site neural, clinical, and cognitive data to discover resting fMRI-based biotypes of PTSD, determine their reliability and replicability, and relationship to symptoms, comorbidities, and cognition. Veterans' imaging and clinical data will come primarily from the VA Boston (n>500) as well as a replication site at the Houston VA (n>200). An additional 300 participants will be recruited for a state-of-the-art cognitive battery, to determine if these biotypes have cognitive signatures that can be inferred from sensitive cognitive tests. Analytically the research will use a general set of techniques at the forefront of an exciting new era for brain imaging- MRI-based “fingerprinting”, or measuring and modeling the reproducible and yet substantial individual variation in the fMRI-based connectome (functional connectivity). OBJECTIVES. Aim 1. Using existing data (n>500), we will A) Define distinct biotypes of PTSD using patterns of fMRI connectivity. We will further test the reliability of these biotypes across two consecutive resting scans, and the ability to predict PTSD biotype in individual Veterans. We will also explore if certain symptoms and comorbidities differentially cluster with PTSD biotypes. Aim 2. We will determine the across- time reliability of these biotypes by examining repeated assessments of the same participants 1-2 years later (n>300). Aim 3. We will validate these biotypes in an independent replication data set, from the Houston VA (n>200 Veterans). Aim 4. We will collect a comprehensive state-of-the-art cognitive battery (n=300) measuring PTSD-specific mechanisms (e.g., fear learning, inhibitory control, attentional bias) to determine if these biotypes can be inferred from cognitive performance profiles.