Functional Significance of Structural Brain Change During Cognitive Remediation in Early Schizophrenia

7.项目摘要/摘要 精神分裂症的特点是严重的功能残疾，这给患者带来了巨大的负担， 他们的照顾者和社会。精神分裂症的现有治疗方法并不是压倒性的 成功地重建先前的功能能力。认知补救治疗显示出相当大的潜力 承诺解决不良的功能结果，但治疗方案的优化因缺乏 支持改善功能恢复的主动神经机制的知识。累进损失 额叶边缘灰质是精神分裂症最常见的重复发现之一，并且显著 对长期结果的预测。认知补救可能达到其效果，部分是通过防止 早期精神分裂症的灰质丢失(或灰质增加)，可以有针对性地改善 功能恢复。NIMH的当务之急是研究心理社会治疗的神经生物学效应 将确定神经治疗的目标和改善的机制途径。不幸的是，这样的研究 是罕见的，因为可以将治疗、大脑和功能结果数据联系起来的翻译研究人员是 极其罕见。因此，这一博士后个人国家研究服务奖(F31)的目的 是为申请者，一名训练有素的临床社会工作者，提供独特的基础认知培训 神经科学研究和纵向神经影像数据分析。培训计划的重点相当明确 为申请者提供所需的实践经验，了解开展 神经成像研究(例如，数据收集和生成)以及在 临床试验。培训和研究目标将在NIMH资助的正在进行的多站点范围内进行 认知增强疗法的随机对照试验(CET；脑成像，认知增强 和早期精神分裂症；R01 MH-92440；Keshavan和Eack，PI；N=86)。新奇的研究计划 Proposed将研究CET与AN相关的额叶-边缘脑改变的功能意义 强化支持性对照疗法在早期精神分裂症中的应用拟议研究的具体目标 将为申请人提供绝佳而独特的培训机会的计划是：(1)复制 CET对功能结局的有效性，(2)检验改进后的结构神经相关 功能，以及(3)确定结构神经机械通路，以改善相关的功能 大学英语四级考试。总之，这些活动将支持申请者成为一名 独立研究人员致力于通过开发、改进和治疗精神分裂症 测试神经科学知情的干预措施以促进功能恢复。预计这项研究 将导致围绕神经靶点和治疗生物标记物的新发现，这将有助于完善认知 补救措施。这项研究的发现也对理解 精神分裂症患者的脑功能障碍和可塑性及其对功能恢复的贡献。

7. PROJECT SUMMARY/ABSTRACT Schizophrenia is characterized by severe functional disability, which places great burden on patients, their caregivers, and society. The available treatments for schizophrenia have not been overwhelmingly successful at reestablishing prior functional abilities. Cognitive remediation treatments display considerable promise for addressing poor functional outcome, but optimization of treatment protocols is impeded by a lack of knowledge of active neural mechanisms that can support improved functional recovery. Progressive loss of fronto-limbic gray matter is one of the most commonly replicated findings in schizophrenia, and is significantly predictive of long-term outcome. Cognitive remediation may achieve its effects, in part, by protecting against gray matter loss (or increasing gray matter) in early course schizophrenia, which can be targeted to improve functional recovery. An NIMH priority is to research the neurobiological effects of psychosocial treatments that will identify neural treatment targets and mechanistic pathways of improvement. Unfortunately, such studies are rare because translational investigators who can connect treatment, brain, and functional outcome data are exceedingly rare. Therefore, the purpose of this Predoctoral Individual National Research Service Award (F31) is to provide the applicant, a trained clinical social worker, with unique training in foundational cognitive neuroscience research and longitudinal neuroimaging data analysis. The training plan is considerably focused on providing the applicant with needed hands-on experience in the practical elements of conducting a neuroimaging study (e.g., data collection and generation) and the analysis of neuroimaging data within a clinical trial. Training and research goals will take place in the context of an ongoing NIMH-funded multi-site randomized-controlled trial of Cognitive Enhancement Therapy (CET; Brain Imaging, Cognitive Enhancement and Early Schizophrenia; R01 MH-92440; Keshavan and Eack, PIs; N = 86). The novel research plan proposed will examine the functional significance of fronto-limbic brain alterations associated with CET vs. an enriched supportive comparison therapy in early-course schizophrenia. Specific aims of the proposed research plan that will provide an excellent and unique training opportunity for the applicant are to (1) replicate the effectiveness of CET on functional outcome, (2) examine the structural neural correlates of improved functioning, and (3) identify structural neural mechanistic pathways toward improved functioning associated with CET. Together, these activities will support the applicant’s long-term career goal to become an independent researcher concentrated on advancing the treatment of schizophrenia by developing, refining, and testing neuroscience-informed interventions to enhance functional recovery. It is expected that this research will lead to new discoveries around neural targets and treatment biomarkers that will help refine cognitive remediation interventions. Findings from this research also have important implications for the understanding of brain dysfunction and plasticity in schizophrenia and their contribution to functional recovery.