Targeting Stress Reactivity in Schizophrenia: Integrated Coping Awareness Therapy

描述(申请人提供)：精神分裂症是最具破坏性的疾病之一，通常导致缺乏功能恢复。尽管有证据表明压力反应失调，但目前专注于纠正症状的治疗在恢复功能方面只取得了很小的成功。在理解精神分裂症患者的变态超负荷的影响方面存在一个根本性的差距，我们理论上认为这与功能缺陷以及脆弱性和复发风险的增加有关。长期目标是 以测试旨在改善应激反应的干预措施。这项应用的目的是开发和测试一种新的治疗干预的可行性，该干预结合了改善应激反应和增加有意义的应对的策略。中心假设是，通过改善由内分泌、免疫和自主神经指数近端衡量的应激反应，干预将导致改善适应能力，更好地发挥作用，降低复发风险，并降低精神分裂症早期患者残疾的可能性。 这项拟议研究的基本原理是，应激反应可能是精神分裂症功能缺陷背后的一个可改变的风险因素。该干预结合了两种治疗方法。第一个是基于研究表明，正念冥想练习与应激事件的神经处理过程的改变有关，并以适应压力的反应为目标。第二个重点是通过积极的心理干预，利用自我产生的适应性情绪，为压力提供缓冲，这可能与建立保护性的社会资源有关。这些免费的干预措施为这一群体提供了一种全面的协同方法，可以导致更具适应性的应对反应，并创建针对压力的缓冲。在强大的初步数据和文献的支持下，这一假说将通过追求三个具体目标来检验：1)开发一种新的干预措施，I-CAT(综合应对意识疗法)，旨在减少应激反应并改善首发精神病患者的功能(R21-阶段1)；2)与6名首发精神病患者(R21-阶段2)一起试验I-CAT和一系列可能的近端(如自主神经、内分泌、应激反应免疫指数、症状严重程度)和远端测量(功能、复发、生活质量)；3)在40人(20人被分配到I-CAT组，20人被分配到支持疗法(ST)(R33-阶段3))的小型随机对照试验的背景下，测试对首发精神病患者实施I-CAT的临床试验的可行性。这种方法是创新的，因为它与目前一系列治疗方法的现状背道而驰，其目标是通过旨在提高应对压力能力的干预措施，实现功能恢复和预防复发。这项拟议的研究意义重大，因为它有望产生一种干预措施，以改善受损的应激反应，这可能会改变精神分裂症的轨迹，降低慢性残疾的可能性和相关的医疗发病率。

DESCRIPTION (provided by applicant): Schizophrenia is one of the most devastating disorders that often results in a lack of functional recovery. Current treatments focused on remediating symptoms have shown only small successes in a return to functioning despite evidence of a dysregulated stress response. There is a fundamental gap in understanding the impact of allostatic overload in persons with schizophrenia that we theorize is associated with deficits in functioning and with an increased vulnerability and relapse risk. The long-term goal is to test an intervention aimed at improving stress reactivity. The objective in this application is o develop and test the feasibility of a novel therapeutic intervention combining strategies to improve stress reactivity and increase meaningful coping. The central hypothesis is that an intervention that improves stress reactivity as measured proximally by endocrine, immune, and autonomic indices will result in improved adaptive capacity, better role functioning, reduced risk of relapse, and decreased likelihood of disability for people in the early stages of schizophrenia. The rationale for the proposed research is that stress reactivity may be a modifiable risk factor underlying functional deficits in schizophrenia. The intervention integrates two treatment approaches. The first is based on research showing that mindfulness meditation practice is associated with alterations in the neural processing of stressful events and targets adaptive responses to stress. The second focuses on providing a buffer against stress by using the self-generation of adaptive emotions with a positive psychology intervention, which is potentially associated with building protective social resources. These complimentary interventions provide a comprehensive synergistic approach for this population that could lead to more adaptive coping responses and create a buffer against stress. Guided by strong preliminary data and support from the literature, this hypothesis will be tested by pursuing three specific aims: 1) To develop a novel intervention, I- CAT (Integrated Coping Awareness Therapy), aimed at reducing stress reactivity and improving functioning in persons with first episode psychosis (R21-Stage 1); 2) To pilot I-CAT and a range of possible proximal (e.g. autonomic, endocrine, immune indices of stress reactivity, symptom severity) and distal measures (function, relapse, quality of life) with six individuals with first episode psychosis (R21-Stage 2); and 3) To test the feasibiliy of a clinical trial implementing I-CAT for people with first episode psychosis in the context of a small randomized controlled trial with 40 individuals (20 assigned to I-CAT and 20 assigned to supportive therapy (ST) (R33-Stage 3)). The approach is innovative because it represents a departure from the status quo of the current array of treatments and targets functional recovery and relapse prevention through an intervention aimed at improving resilience to stress. The proposed research is significant, because it is expected to produce an intervention to ameliorate impaired stress reactivity that has the potential to change the trajectory of schizophrenia and reduce the likelihood of chronic disability and the associated medical morbidity.