Neurobiology of Suicide Risk in Traumatic Brain Injury and Substance Abuse

描述（由申请人提供）： 项目摘要： 努力了解创伤性脑损伤（TBI），前额叶功能和自杀意念的神经生物学相关性，迄今为止提供了不确定的结果。原发性爆炸相关的TBI在退伍军人中很常见，并且似乎产生类似于弥漫性轴索损伤（DAI）的神经生理学变化。支持TBI患者认知处理的脑神经回路中断可能导致执行功能缺陷，包括解决问题和决策能力降低。此外，患有TBI的退伍军人通常患有药物滥用的并发症，并且已经表明使用酒精和非法药物可以进一步损害已知依赖于额叶皮层的执行介导功能。有人提出，这些功能缺陷可能会导致认知僵化和心理困扰，因此可能作为自杀风险的标志。拟议的研究建立在现有的额叶功能的神经生物学模型，并将通过应用功能性磁共振成像（fMRI）和扩散张量成像（DTI）技术扩展我们对TBI相关脑变化的理解。因此，我们将研究血氧水平依赖（BOLD）信号变化扣带和背外侧前额叶皮层以及杏仁核的TBI受试者，有和没有滥用药物的历史，这些模式的信号变化的性质（高/低）与健康对照受试者。我们将确定是否措施的白色物质的微观结构，如测量的DTI方法，是异常的TBI受试者，与健康对照组相比，有和没有物质滥用的历史。我们还将研究BOLD信号变化和FA值降低与自杀意念之间的关系。最后，我们将检验以下假设：物质滥用和非物质滥用TBI退伍军人组中FA减少和额叶激活减少与自杀意念显著相关，并且TBI+物质滥用队列的相关性更强。我们相信，拟议的研究将通过提供对自杀和TBI的神经生物学相关性的重要见解来影响退伍军人的健康，这可能会导致识别和治疗TBI行为后果的新方法。 公共卫生相关性： 叙述：创伤性脑损伤（TBI）是一个重要的医疗问题，积极战斗退伍军人。从持久自由行动/伊拉克自由行动（OEF/OIF）返回的退伍军人，其中许多人患有轻度TBI，强调了了解这种类型脑损伤的神经生物学和神经心理学后果的至关重要性。此外，一些研究指出，迫切需要定义的神经生物学和认知基础的自杀意念和行为的退伍军人与TBI与共病药物滥用/依赖障碍。需要对自杀风险和恢复的神经生理学和认知预测因素进行评估，以改善治疗。我们相信，拟议的研究将通过提供对自杀的神经生物学相关性的重要见解来影响退伍军人的健康，这可能会导致识别和治疗TBI行为后果的新方法。

DESCRIPTION (provided by applicant): Project Summary: Efforts at understanding the neurobiological correlates of traumatic brain injury (TBI), prefrontal function and suicidal ideation have thus far provided inconclusive results. Primary blast-related TBI is common in returning veterans and appears to produce neurophysiological changes that resemble diffuse axonal injury (DAI). Disruptions in brain neural circuits that support cognitive processing in individuals with TBI may result in deficits in executive function including reduced problem solving and decision-making capacity. Moreover, veterans with TBI are often co-morbid for substance abuse and it has been shown that use of alcohol and illicit drugs can further compromise executive mediated functions known to depend on the frontal cortex. It has been proposed that these functional deficits may lead to cognitive rigidity and psychological distress and thus may serve as markers for suicidal risk. The proposed research builds on existing neurobiologic models of frontal function and will extend our understanding of TBI related brain changes by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques. Accordingly, we will examine blood oxygen level dependent (BOLD) signal changes within the cingulate and dorsolateral prefrontal cortices as well as the amygdala in TBI subjects, with and without a history of substance abuse, to characterize the nature of these patterns of signal change (higher/lower) in relation to healthy control subjects. We will determine whether measures of white matter microstructure, as measured by DTI methods, are abnormal in TBI subjects, with and without a history of substance abuse compared with healthy control subjects. We will also examine the relationship between BOLD signal changes and reduced FA values and suicidal ideation. Lastly, we will test the hypothesis that reduced FA and reduced activation in frontal regions in both substance abusing and non- substance abusing TBI veteran groups is significantly correlated with suicidal ideation, and that the correlation will be stronger for the TBI plus substance abuse cohort. We believe the proposed studies will impact veteran's health by providing important insights into the neurobiological correlates of suicide and TBI that may lead to new approaches for identification and treatment of behavioral consequences of TBI. PUBLIC HEALTH RELEVANCE: Narrative: Traumatic brain injury (TBI) is an important medical problem for active combat veterans. The return of veterans from Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF), many of whom have suffered mild TBI, has emphasized the crucial importance of understanding the neurobiologic and neuropsychological consequences of this type of brain injury. Furthermore, several studies point to the urgent need to define the neurobiological and cognitive underpinnings of suicidal ideation and behavior in veterans with TBI with and without comorbid substance abuse/dependence disorders. The evaluation of the neurophysiologic and cognitive predictors of suicide risk and recovery are needed to improve treatments. We believe the proposed studies will impact veteran's health by providing important insights into the neurobiological correlates of suicide that may lead to new approaches for identification and treatment of behavioral consequences of TBI.