Defining biotypes of PTSD with resting-state connectivity

创伤后应激障碍不是一种单一的疾病，而是一种异质性综合征，无论是在其 病理学和治疗反应。尽管我们的研究取得了重大突破， 了解与PTSD相关的神经生物学通路，其神经生物学异质性 阻碍了一致的生物标志物的鉴定，这仍然是难以捉摸的。以前工作的一个主要局限性 PTSD的临床症状和行为亚型并不能充分捕捉到 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 机制等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， 根据大脑的共同模式识别神经生理学亚型或PTSD的生物型 静息功能磁共振成像连接功能障碍。以下旨在发现和验证基于MRI的 我们退伍军人中PTSD的生物型具有广泛的未来应用，例如改善客观诊断， 工具，提供干预目标，并预测谁将对特定治疗作出反应。 设计和方法：目前的建议将使用多个地点的神经，临床和认知数据， 发现PTSD的静息fMRI生物型，确定其可靠性和可复制性，以及与 症状、合并症和认知。退伍军人的成像和临床数据将主要来自VA Boston（n>500）以及Houston VA（n>200）的复制位点。另外300名与会者将 招募他们进行最先进的认知电池测试，以确定这些生物型是否具有认知特征， 可以从敏感的认知测试中推断出来。分析研究将使用一套通用的技术， 大脑成像激动人心的新时代的前沿--基于MRI的“指纹”，或测量和建模 基于fMRI的连接体中可再现的但实质性的个体差异（功能性的 连接性）。 目标.目标1.使用现有的数据（n>500），我们将A）定义PTSD的不同生物型， 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，以及预测个体退伍军人PTSD生物型的能力。我们还将探讨，如果某些 症状和合并症与PTSD生物型不同地聚集。目标2.我们会决定- 这些生物型的时间可靠性，通过检查1-2年后相同参与者的重复评估 （n>300）。目标3：我们将验证这些生物型在一个独立的复制数据集，从休斯敦弗吉尼亚州 （n>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PTSD特异性机制（例如，恐惧学习，抑制控制，注意力偏差），以确定是否 这些生物型可以从认知表现概况中推断出来。

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.