Negative Valence Systems in Schizophrenia

精神分裂症中的负价系统

• 批准号: 10275869
• 负责人: JENNIFER URBANO BLACKFORD
• 金额: $ 73.71万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275869
• 关键词: Acute; Address; Amygdaloid structure; Animal Model; Anxiety; Anxiety Disorders; Aversive Stimulus; Behavior; Brain; Brain region; Clinical; Cognition; Data; Delusions; Detection; Development; Dimensions; Disease; Distress; Emotions; Foundations; Fright; Functional Magnetic Resonance Imaging; Future; Galvanic Skin Response; Human; Hydrocortisone; Impairment; Individual; Intervention; Knowledge; Light; Measures; Mediating; Mental disorders; Methods; Modeling; Motor; Negative Valence; Neurobiology; Outcome; Paranoia; Pattern; Physiological; Physiology; Pilot Projects; Play; Prefrontal Cortex; Prevalence; Quality of life; Research; Research Domain Criteria; Resolution; Rest; Rodent; Role; Schizophrenia; Sensory; Social Functioning; Stimulus; Structure; Structure of terminal stria nuclei of preoptic region; Subgroup; Symptoms; System; Testing; Uncertainty; anxiety symptoms; base; biological adaptation to stress; common symptom; comorbidity; conditioned fear; experience; in vivo; neurobiological mechanism; neuroimaging; novel; response; severe mental illness; suicidal risk

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.

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 精神分裂症的神经网络导致了精神分裂症的症状，比如妄想和妄想。迄今为止 精神分裂症的情绪研究主要集中在恐惧处理上， 杏仁核对中性刺激的反应和杏仁核-前额叶皮层连接的改变。但最近的 研究表明，大脑的另一个区域--终纹床核（BNST）--可能起着 BNST介导的焦虑与杏仁核介导的恐惧不同。RDoC的 负价系统认识到这种恐惧焦虑的区别，并有单独的结构， 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 在精神分裂症患者中进行了检查。使用我们实验室开创的研究人类BNST的方法，我们 已经收集了精神分裂症的初步数据我们的试验数据为BNST连通性提供了初步证据 对不可预测的威胁的反应，对潜在伤害结构的反应的测量， 在精神分裂症患者与健康对照组相比的静息状态下。此外，我们发现 有证据表明，精神分裂症患者的BNST改变对于那些患有或不患有共病焦虑症的人来说是不同的。 患有精神分裂症和焦虑症的个体表现出BNST和 与精神分裂症患者相比，多个大脑区域参与威胁检测、不确定性和焦虑 也没有焦虑症目前的研究将调查三组的BNST连接： 精神分裂症伴焦虑障碍（SZ+ANX），精神分裂症患者无焦虑障碍共病 焦虑症（SZ-ANX）和健康对照（HC）。我们假设精神分裂症患者 改变了BNST的连接性以应对不可预测的威胁并改变了BNST的内在连接性 相对于HC。此外，我们预测SZ+ANX组将显示相对于SZ- ANX.我们将以三个具体目标来检验这些假设。(1)调查BNST连接，以响应 精神分裂症个体中不可预测的威胁;（2）确定BNST是否存在差异 精神分裂症患者的内在连接性;（3）BNST连接性之间关系的测试， 应激反应（皮肤电导和皮质醇）和精神分裂症的临床症状。鉴于 精神分裂症中焦虑的患病率，精神分裂症中的BNST改变很可能并可能导致新的 精神分裂症情绪改变的神经生物学机制。的结果 这项研究可以为未来精神分裂症情绪的研究提供基础，确定是否 焦虑亚组之间存在神经生物学差异，并指导小说的发展 神经科学的治疗方法。