Neurobiology of Dissociation

在第5版DSM中，介绍了创伤后应激障碍(PTSD)的一个亚型，该亚型的特征是附加的分离症状。在DSM-5中，分离被定义为“意识、记忆、身份或对环境的感知的通常综合功能的破坏”。有关人士表示，他们对自己或环境有超然的感觉。此外，情绪和身体意识可能会受到严重损害。初步研究表明，与没有明显分离症状的创伤后应激障碍患者相比，分离亚型的创伤后应激障碍患者的症状严重程度更高，从传统创伤治疗中获益的程度较小。到目前为止，还没有经验数据可以解释解离是如何产生的，以及哪些神经生物学变化表征了它。目前的建议试图调查两种PTSD亚型的潜在神经机制：众所周知的侵入性亚型以及最近引入的解离型。两组患者都在功能磁共振扫描仪中接受安慰剂对照的药物挑战范例。在安慰剂条件下，自然诱发的分离将根据组间设计中的神经元变化进行分析。药物条件的目的是检验因果假说，即增强解离是由选择性的去甲肾上腺素介导的杏仁核活动增强引起的，随后通过前额叶过度调节下调杏仁核活动。两种暴露范式(阈值下和阈值上)的结合使得能够分析关于初始自下而上过程和调节自上而下激活的群体差异。在阈下暴露期间，安慰剂和制剂条件下杏仁核中的个体激活差异将被用来预测在阈值上暴露期间前额叶调节区的激活差异。当前项目的继续不仅将确保相关分析，而且能够测试分离原因的因果假说，并确定分离诱导的神经激活的变化。

In the 5th edition of die DSM, a subtype of posttraumatic stress disorder (PTSD) was introduced which is characterized by additional symptoms of dissociation. In the DSM-5, dissociation is defined as a 'disruption of the usually integrated functions of consciousness, memory, identity or perception of the environment'. Persons concerned report feelings of detachment from oneself or from the environment. In addition, emotional and bodily awareness may be severely impaired. Initial studies suggest that PTSD-patients of the dissociative subtype show increased symptom severity and benefit to a lesser extent from conventional trauma therapies compared to PTSD-patients without pronounced dissociative symptoms. To date, no empirical data are available which could explain how dissociation arises and which neurobiological alterations characterize it. The current proposal seeks to investigate the underlying neuronal mechanism of both PTSD subtypes: the well-known intrusive subtype as well as the recently introduced dissociative subtype. Both patient groups undergo a placebo-controlled, pharmacological challenge paradigm in the fMRI scanner. In the placebo condition, the naturally evoked dissociation will be analyzed with regard to neuronal alterations in a between-group design. The agent condition serves the purpose of testing the causal hypothesis that enhanced dissociation is caused by a selective, norepinephrine-mediated boost of amygdala activity which is subsequently down-regulated via prefrontal overmodulation. The combination of two exposure paradigms (subliminal and supraliminal) enables the analysis of group differences concerning both the initial bottom-up processes and the regulatory top-down activation. Individual activation differences in the amygdala between the placebo and agent conditions during subliminal exposure will be employed as a predictor of activation differences in prefrontal regulation areas during supraliminal exposure. The continuation of the current project will not only ensure correlational analyses but enable to test a causal hypothesis of the etiology of dissociation and to determine dissociation-induced alterations in neural activations.