Negative Valence Systems in Schizophrenia

精神分裂症是一种严重的异质性精神障碍，影响大多数功能领域，包括 行为、认知和情感。最近的模型强调了情绪大脑的重要变化 精神分裂症中的网络导致精神分裂症症状，如妄想症和妄想症。到目前为止， 对精神分裂症患者情绪的研究主要集中在恐惧的处理上，并显示出 杏仁核对中性刺激的反应和杏仁核-前额叶皮质连接的改变。然而，最近 研究表明，大脑的另一个区域--终纹床核(BNST)--可能扮演着 BNST介导的焦虑与杏仁核介导的恐惧是不同的。RDoC的 负价系统认识到这种恐惧-焦虑的区别，并有不同的反应结构 急性威胁(杏仁核)和对潜在伤害的反应(BNST)。据我们所知，BNST还没有 在精神分裂症患者身上进行检查。使用我们实验室首创的方法来研究人类BNST，我们 已经收集了精神分裂症的初步数据。我们的试点数据为BNST连接提供了初步证据 对不可预测的威胁的反应，对潜在危害的反应的一种衡量标准， 以及精神分裂症患者在休息状态下与健康对照组的比较。此外，我们发现， 有证据表明，精神分裂症的BNST改变对于那些有或没有共病焦虑的人来说是不同的。 精神分裂症和焦虑症患者表现出更强的BNST和 与精神分裂症患者相比，参与威胁检测、不确定性和焦虑的多个大脑区域 也没有焦虑症。目前的研究将在三组人中调查BNST连接性：患有 精神分裂症合并焦虑症(SZ ANX)，无共病的精神分裂症患者 焦虑症(SZ-ANX)和健康对照组(HC)。我们假设精神分裂症患者 已更改BNST连接以应对不可预测的威胁，并更改了BNST固有连接 相对于HC。此外，我们预测相对于SZ-ANX，SZ ANX组将表现出BNST超连通性 ANX。我们将用三个具体目标来检验这些假说。(1)调查BNST连接以响应 精神分裂症患者的不可预测的威胁；(2)确定BNST是否有差异 精神分裂症患者的内在连接性；(3)BNST连接性之间的关系测试， 精神分裂症的应激反应(皮肤电导和皮质醇)和临床症状。给定 精神分裂症中焦虑的患病率，精神分裂症中BNST的改变可能会产生新的 精神分裂症情绪改变的神经生物学机制。结果来自于 所提出的研究可以为未来精神分裂症的情绪研究提供基础，确定是否 焦虑亚群存在神经生物学差异，并指导小说的发展 神经科学的知情治疗。

Schizophrenia is a severe and heterogeneous mental disorder that impacts most domains of function including behavior, cognition, and emotion. Recent models have highlighted important alterations of the emotion brain networks in schizophrenia that contribute to schizophrenia symptoms, like paranoia and delusions. To date, the studies of emotion in schizophrenia have primarily focused on fear processing and have shown heightened amygdala responses to neutral stimuli and altered amygdala-prefrontal cortex connectivity. However, recent research suggests that another brain region—the bed nucleus of the stria terminalis (BNST)—may play a critical role in anxiety and that BNST-mediated anxiety is distinct from amygdala-mediated fear. The RDoC’s Negative Valence System recognizes this fear-anxiety distinction and has separate constructs for Response to Acute Threat (amygdala) and Response to Potential Harm (BNST). To our knowledge, the BNST has yet to be examined in individuals with schizophrenia. Using methods pioneered by our lab to study the human BNST, we have collected preliminary data in schizophrenia. Our pilot data provides initial evidence for BNST connectivity differences in both response to unpredictable threat, a measure of the response to potential harm construct, and during a resting state in individuals with schizophrenia compared to healthy controls. Further, we found evidence that BNST alterations in schizophrenia differ for those who do or do not have comorbid anxiety. Individuals with schizophrenia and anxiety disorders demonstrated stronger connectivity between BNST and multiple brain regions involved in threat detection, uncertainty, and anxiety relative to those with schizophrenia and no anxiety disorder. The current study will investigate BNST connectivity in three groups: individuals with schizophrenia with a comorbid anxiety disorder (SZ+ANX), individuals with schizophrenia without a comorbid anxiety disorder (SZ-ANX), and healthy controls (HC). We hypothesize that individuals with schizophrenia will have altered BNST connectivity in response to unpredictable threat and altered BNST intrinsic connectivity relative to HC. In addition we predict that SZ+ANX group will show BNST hyperconnectivity relative to SZ- ANX. We will test these hypotheses with three specific aims. (1) Investigate BNST connectivity in response to unpredictable threat in individuals with schizophrenia; (2) Determine whether there are differences in BNST intrinsic connectivity in individuals with schizophrenia; (3) Test for relationships among BNST connectivity, stress responses (skin conductance and cortisol), and clinical symptoms in schizophrenia. Given the prevalence of anxiety in schizophrenia, BNST alterations within schizophrenia are likely and may shed new light on the neurobiological mechanisms underlying emotion alterations in schizophrenia. The results from the proposed study can provide a foundation for future studies of emotion in schizophrenia, determine whether there are neurobiological differences in anxiety subgroups, and guide the development of novel neuroscientifically-informed treatments.