Twin Study of Biologic Markers for PTSD

描述(申请人提供)：这个补充项目将利用一个独特的机会，在越南一群不适合战斗暴露的同卵双胞胎中，为正在进行的创伤后应激障碍(PTSD)生物异常调查增加一项重要的神经成像研究。拟议的研究有两个主要目标。第一项是测试患有创伤后应激障碍的越战退伍军人和没有创伤后应激障碍的退伍军人在三个感兴趣区(ROI)，即杏仁核、前扣带回(ACC)和海马区静息脑代谢活动(ROI)的差异。ACC将进一步细分为背侧、吻侧(前)和腹侧(膝下/穹隆下)。第二个主要目标是评估所发现的任何静息大脑代谢差异的来源。将测试两个主要的可能来源：创伤后应激障碍的家族易感性因素与后天创伤后应激障碍症状。因变量为静息脑局部葡萄糖代谢率(RCMRglu)，由18F-氟代脱氧葡萄糖正电子发射断层扫描(PET FDG)确定。PET图像将与结构磁共振图像(MRI)共同配准，先验ROI将在其上进行形态测量。双胞胎受试者已经在马萨诸塞州综合医院参加了功能磁共振和心理生理学研究，其中将增加PET FDG程序。统计学意义将通过一个混合模型进行检验，该模型将创伤后应激障碍诊断(即，战斗暴露的双胞胎中与战斗相关的创伤后应激障碍与非创伤后应激障碍)视为对间固定效应，将战斗暴露作为对内固定效应，将双胞胎对作为随机效应，并辅以专门解决先验假设的计划的学生t检验。除了主要的ROI分析外，还将进行统计参数图(SPM)，以便保留在先验选定的ROI之外的区域确定重大影响的可能性，并评估任何项目ROI中重要发现的特殊性。这一结果有望促进我们对创伤后应激障碍神经生理学异常的体质性和获得性的理解，以及这种疾病的发病机制。结果还可能对筛选暴露于军事战斗或其他严重应激源时发生创伤后应激障碍的高危人群产生影响。

DESCRIPTION (provided by applicant): This supplementary project will take advantage of a unique opportunity to add an important neuroimaging study to an ongoing investigation of biologic abnormalities in post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The proposed study has two major objectives. The first is to test for group differences in resting cerebral metabolic activity in three regions of interest (ROIs), viz., amygdala, anterior cingulate cortex (ACC), and hippocampus, in Vietnam combat veterans with vs. without PTSD. ACC will be further subdivided into dorsal, rostral (pregenual), and ventral (subgenual/subcallosal) divisions. The second major objective is to evaluate the origin of any resting cerebral metabolic differences that are found. Two major possible origins will be tested: familial vulnerability factor for PTSD vs. acquired PTSD sign. The dependent variable will be resting regional cerebral metabolic rates for glucose (rCMRglu) as determined by 18F-fluorodeoxyglucose positron emission tomography (PET FDG). PET images will be co-registered with structural magnetic resonance images (MRIs) on which the a priori ROIs will be morphometrically delineated. Twin subjects will already be participating in functional MRI and psychophysiology studies at the Massachusetts General Hospital, to which the PET FDG procedure will be added. Statistical significance will be tested by means of a mixed model that treats PTSD Diagnosis (i.e., combat-related PTSD vs. non-PTSD in the combat-exposed twin) as a between-pairs fixed effect, combat Exposure as a within-pair fixed effect, and twin pairs as a random effect, supplemented by planned Student's t-tests that specifically address the a priori hypotheses. In addition to the primary ROI analyses, statistical parametric mapping (SPM) will be performed in order to preserve the possibility of identifying significant effects in regions outside the a priori selected ROIs, and to evaluate the specificity of important findings in any of the project's ROIs. Results are expected to advance our understanding of the constitutional vs. acquired nature of neurophysiologic abnormalities in PTSD and the pathogenesis of this disorder. Results may also have implications for the screening of persons at high risk for the development of PTSD upon exposure to military combat or other severe stressors.