Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors
Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors
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DOI：
10.1038/s41398-020-00898-z
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发表时间：
2020-06-27
影响因子：
6.8
通讯作者：
Hendler, Talma
中科院分区：
文献类型：
--
作者：
Ben-Zion, Ziv;Zeevi, Yoav;Hendler, Talma
当代创伤后应激障碍（PTSD）的诊断主要是基于主观的人际报告，而忽略了相关的神经行为机制。以前的研究与PTSD的生物标志物大多使用的主要结果的措施，忽视了广泛的变异性和丰富的PTSD表型特征的诊断为基础。在这里，我们的目的是计算得出潜在的生物标志物，可以有效地区分创伤后应激障碍亚型之间的最近的创伤幸存者。使用三阶段半无监督方法（“3C”）首先根据当前PTSD症状严重程度对个体进行分类，然后基于与PTSD相关的临床特征（例如焦虑和抑郁）导出聚类，最后使用客观多域特征对参与者的聚类成员进行分类。从创伤暴露后1个月内评估的101名成年平民（年龄= 34.80 +/- 11.95; 51名女性）的心理测量学、认知功能以及结构和功能MRI数据中提取了共256个特征。通过重要性分析、分类树和方差分析对最能区分聚类成员的特征进行了评估。结果显示，内嗅和喙前扣带皮层体积（结构MRI域），在任务杏仁核的功能连接与丘脑和丘脑（功能MRI域），执行功能和认知灵活性（认知测试域）最好区分与PTSD严重程度相关的两个集群。交叉验证确定了该样品中结果的稳健性和一致性。3C分析揭示的神经和认知潜在生物标志物提供了创伤后不久创伤后发病率的客观分类器。他们还映射到以前记录的与创伤后应激障碍相关的神经行为机制，并证明了标准化和客观的测量在创伤后不久区分临床亚类的有用性。
Contemporary symptom-based diagnosis of post-traumatic stress disorder (PTSD) largely overlooks related neurobehavioral mechanisms and relies entirely on subjective interpersonal reporting. Previous studies associating biomarkers with PTSD have mostly used symptom-based diagnosis as the main outcome measure, disregarding the wide variability and richness of PTSD phenotypical features. Here, we aimed to computationally derive potential biomarkers that could efficiently differentiate PTSD subtypes among recent trauma survivors. A three-staged semi-unsupervised method ("3C") was used to firstly categorize individuals by current PTSD symptom severity, then derive clusters based on clinical features related to PTSD (e.g. anxiety and depression), and finally to classify participants' cluster membership using objective multi-domain features. A total of 256 features were extracted from psychometrics, cognitive functioning, and both structural and functional MRI data, obtained from 101 adult civilians (age = 34.80 +/- 11.95; 51 females) evaluated within 1 month of trauma exposure. The features that best differentiated cluster membership were assessed by importance analysis, classification tree, and ANOVA. Results revealed that entorhinal and rostral anterior cingulate cortices volumes (structural MRI domain), in-task amygdala's functional connectivity with the insula and thalamus (functional MRI domain), executive function and cognitive flexibility (cognitive testing domain) best differentiated between two clusters associated with PTSD severity. Cross-validation established the results' robustness and consistency within this sample. The neural and cognitive potential biomarkers revealed by the 3C analytics offer objective classifiers of post-traumatic morbidity shortly following trauma. They also map onto previously documented neurobehavioral mechanisms associated with PTSD and demonstrate the usefulness of standardized and objective measurements as differentiating clinical sub-classes shortly after trauma.