Neurobiology of Suicide Risk in Traumatic Brain Injury and Substance Abuse

项目摘要 努力了解创伤性脑损伤(TBI)、前额叶功能和 到目前为止，自杀意念提供了不确定的结果。原发冲击波相关的创伤性脑损伤在返乡时很常见 而且似乎会产生类似弥漫性轴索损伤(DAI)的神经生理学变化。 脑外伤患者支持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下降。此外， 患有脑外伤的退伍军人经常合并药物滥用，而且有证据表明，使用酒精和非法药物 药物可以进一步损害已知的依赖额叶皮质的执行调节功能。一直以来 提出这些功能缺陷可能导致认知僵化和心理痛苦，从而可能 作为自杀风险的标志。这项拟议的研究建立在现有的额叶神经生物学模型的基础上 功能，并将通过应用功能磁学来扩展我们对脑外伤相关脑变化的理解 磁共振成像(FMRI)和扩散张量成像(DTI)技术。因此，我们将对血液进行检测 扣带回和背外侧前额叶皮质内氧水平依赖(BOLD)信号的变化 作为脑外伤受试者的杏仁核，有和没有药物滥用史，以表征 这些信号变化模式(高/低)与健康对照受试者有关。我们将确定是否 用DTI方法测量的脑白质微观结构在脑外伤患者中是异常的，有 与健康对照组相比，无药物滥用史的受试者。我们还将研究 大胆信号改变和FA值降低与自杀意念之间的关系。最后，我们将测试 在物质滥用和非物质滥用中减少FA和减少额区激活的假说 物质滥用与脑外伤老兵自杀意念显著相关，且这种相关性 对于TBI加药物滥用队列来说将会更强。我们相信，拟议的研究将影响退伍军人的 通过提供对自杀和脑外伤的神经生物学关联的重要见解，可能导致 识别和治疗脑外伤行为后果的新方法。

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.