Twin Study of Biologic Markers for PTSD

PTSD 生物标志物的双胞胎研究

• 批准号: 8077444
• 负责人: Lisa M Shin
• 金额: $ 73.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8077444
• 关键词: Abbreviations; Address; Age; Alleles; Amygdaloid structure; Anterior; Aspartate; Biological Markers; Brain; Brain region; Candidate Disease Gene; Cells; Cerebrovascular Circulation; Chemicals; Cognitive; Conflict (Psychology); Constitutional; Cytosine; DNA; Data; Diagnosis; Diagnostic; Direct Costs; Disease; Dizygotic Twins; Dorsal; Environment; Epigenetic Process; Event; Exposure to; Extinction (Psychology); Face; Facial Expression; Failure; Force of Gravity; Fright; Functional Magnetic Resonance Imaging; Galvanic Skin Response; General Hospitals; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genotype; Guanine; Heredity; Hippocampus (Brain); Human; Imagery; Individual; Investigation; Life; Lymphocyte; Magnetic Resonance Spectroscopy; Massachusetts; Measures; Mediator of activation protein; Messenger RNA; Methylation; Minor; Monozygotic Twinning; Monozygotic twins; Nature; Neuroanatomy; Neurons; Nomenclature; Pathogenesis; Pattern; Peripheral; Persons; Phenotype; Physiological; Population; Positron-Emission Tomography; Post-Traumatic Stress Disorders; Prefrontal Cortex; Preventive Intervention; Process; Protocols documentation; Protons; Recruitment Activity; Relative (related person); Research; Risk; Risk Factors; Screening procedure; Series; Shock; Signal Transduction; Site; Source; Staging; Stimulus; Stressful Event; Study Subject; System; Techniques; Testing; Text; Travel; Twin Multiple Birth; Twin Studies; Veterans; Vietnam; Work; acquired factor; base; blood oxygen level dependent; cingulate cortex; combat; conditioned fear; design; disorder risk; endophenotype; experience; face mask; follow-up; high risk; improved; inorganic phosphate; male; mental imagery; neuroimaging; public health relevance; research study; response; showing emotion

DESCRIPTION (provided by applicant): This competing continuation proposal will take advantage of a unique opportunity to further follow up on a series of investigations of the origin of biologic markers for post-traumatic stress disorder (PTSD) in a population of identical twins discordant for combat exposure in Vietnam. The main possible marker origins to be addressed are: a.) familial vulnerability for PTSD vs. b.) acquired PTSD sign. Familial vulnerability will be evaluated by examining the main effect of between-pair Diagnosis (PTSD vs. non- PTSD in the combat-exposed twin), as well as by contrasting the (high-risk) combat-unexposed co-twins of combat-exposed twins with PTSD vs. the (low-risk) combat-unexposed co-twins of combat-exposed twins without PTSD. Acquired PTSD sign will be evaluated by examining the interaction between Diagnosis and within-pair Exposure (combat vs. no combat), as well as by contrasting the PTSD combat twins vs. their own combat-unexposed co-twins. Recent pilot data suggest that the following may be familial vulnerability factors for PTSD: a.) decreased rostral anterior cingulate cortex (rACC) and increased amygdala activation during passive viewing of overt fearful facial expressions during fMRI, and b.) increased dorsal ACC activation during a multi-source interference task (MSIT) during fMRI. In contrast, pilot data suggest that c.) impaired retention of extinction of a psychophysiologic conditioned fear response may be an acquired PTSD sign. The work in this competing continuation proposal will include testing the above three pilot findings in additional twin subjects in an attempt to obtain definitive results. Finding (c) will also be pursued using fMRI. Additional experiments will include measuring d.) regional cerebral blood flow during script-driven imagery of combat and other personal stressful events during positron emission tomography, and e.) n- acetyl aspartate levels in dACC, rACC, ventromedial prefrontal cortex, and hippocampus by magnetic resonance spectroscopy. Twin subjects will be invited travel to the Massachusetts General Hospital for two days of neuroimaging protocols. Results are expected to advance our understanding of the constitutional vs. acquired nature of biologic abnormalities in PTSD and the neuroanatomy and pathogenesis of this disorder. Additionally the proposed research may identify biologic mediators of the effects of candidate genes on risk for PTSD. PUBLIC HEALTH RELEVANCE: This study will attempt to further resolve the origin of biologic abnormalities in post-traumatic stress disorder (PTSD) by determining whether or not they are present in the identical twins of combat veterans with PTSD. Abnormalities that are found to be acquired could become the target of PTSD treatments, whereas abnormalities that serve as risk factors for PTSD could be used in screening for persons at risk and possible preventive interventions.

描述（由申请人提供）：这项竞争性延续提案将利用一个独特的机会，进一步跟进一系列关于创伤后应激障碍（PTSD）生物标志物起源的调查，这些调查是在越南战斗暴露不一致的同卵双胞胎群体中进行的。要解决的主要可能的标记来源是：a.) PTSD 家族易感性与 b.) 获得性 PTSD 迹象。家庭脆弱性将通过检查配对间诊断（遭受战斗的双胞胎中的 PTSD 与非 PTSD）的主要影响来评估，以及通过对比患有 PTSD 的战斗暴露双胞胎的（高风险）未暴露于战斗的双胞胎与没有 PTSD 的战斗暴露双胞胎的（低风险）未暴露于战斗的双胞胎进行比较。将通过检查诊断和配对内暴露（战斗与非战斗）之间的相互作用，以及通过对比 PTSD 战斗双胞胎与他们自己的未暴露战斗双胞胎来评估获得性 PTSD 迹象。最近的试点数据表明，以下可能是 PTSD 的家族性脆弱因素：a.) 在 fMRI 期间被动观看明显恐惧的面部表情期间，头端前扣带皮层 (rACC) 减少，杏仁核激活增加；b.) 在 fMRI 期间多源干扰任务 (MSIT) 期间，背侧 ACC 激活增加。相反，试点数据表明，c.) 心理生理条件性恐惧反应的消退保留受损可能是一种获得性 PTSD 迹象。这项竞争性延续提案中的工作将包括在其他双胞胎受试者中测试上述三项试点结果，以期获得明确的结果。 (c) 的发现也将通过功能磁共振成像来实现。其他实验将包括测量 d.) 在正电子发射断层扫描期间脚本驱动的战斗图像和其他个人压力事件期间的局部脑血流量，以及 e.) 通过磁共振波谱仪测量 dACC、rACC、腹内侧前额叶皮层和海马体中的 n-乙酰天冬氨酸水平。双胞胎受试者将被邀请前往马萨诸塞州总医院进行为期两天的神经影像检查。预计结果将促进我们对 PTSD 生物异常的先天性与后天性以及该疾病的神经解剖学和发病机制的理解。此外，拟议的研究可能会确定候选基因对 PTSD 风险影响的生物介质。公共健康相关性：本研究将尝试通过确定患有 PTSD 的退伍军人的同卵双胞胎中是否存在生物学异常来进一步解决创伤后应激障碍 (PTSD) 的生物学异常的起源。发现的获得性异常可能成为 PTSD 治疗的目标，而作为 PTSD 危险因素的异常可用于筛查高危人群和可能的预防干预措施。