Brain Imaging, Cognitive Enhancement and Early Schizophrenia

脑成像、认知增强和早期精神分裂症

• 批准号: 8644914
• 负责人: MATCHERI S. KESHAVAN
• 金额: $ 60.76万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644914
• 关键词: Address; Aftercare; Behavior; Behavioral; Brain; Brain imaging; Brain region; Caring; Chronic; Chronic Schizophrenia; Cognition; Cognitive; Data; Disease; Early Intervention; Functional Imaging; Functional Magnetic Resonance Imaging; Goals; Imaging Techniques; Impaired cognition; Impairment; Intervention; Link; Magnetic Resonance Imaging; Mediating; Mental disorders; National Institute of Mental Health; Neurocognition; Neurocognitive; Neuronal Plasticity; Outcome; Patients; Phase; Physical shape; Randomized; Relative (related person); Resources; Sampling; Schizophrenia; Strategic Planning; Structure; Supportive care; Testing; Therapeutic; active method; cognitive enhancement; cognitive rehabilitation; design; functional disability; functional gain; functional improvement; functional outcomes; gray matter; imaging modality; improved; information gathering; neuroimaging; neuromechanism; neuroprotection; non-drug; novel; prevent; public health relevance; randomized trial; relating to nervous system; social; social cognition; social rehabilitation; treatment response

DESCRIPTION (provided by applicant): Schizophrenia is frequently characterized by a disabling and lifelong course of illness, making it imperative that interventions to alter its deleterious effects be applied as early as possible. Cognitive impairments are among the most disabling aspects of the illness, and represent critical targets for early intervention. Our earlier studies have shown that cognitive rehabilitation approaches designed to capitalize on existing brain resources and enhanced neuroplasticity demonstrate significant promise for improving cognition and functional outcome in early course schizophrenia. These beneficial effects of cognitive rehabilitation presumably reflect alterations in the structural and functional integrity of the brain. We have observed exciting preliminary evidence from our recently completed early course trial of Cognitive Enhancement Therapy (CET) indicating that the early application of this novel neurocognitive and social-cognitive rehabilitation approach can prevent fronto-temporal gray matter loss in early course schizophrenia. Beyond our preliminary observations, however, remarkably little is known about the effects of cognitive rehabilitation on diverse functional and structural brain parameters early in the disorder. The capacity of the schizophrenia brain to respond to non-pharmacologic intervention is of substantial significance, and identifying the effects of cognitive rehabilitation on the brain in early course schizophrenia is critical for elucidating the neurobiologic mechanisms of action of these approaches, clarifying the requisite brain changes that can support cognitive enhancement, and refining current treatments. This project proposes to study the effects of CET on brain function and structure in early course schizophrenia. Patients in the early course of the disorder (illness duration < 5 years) will be randomly assigned to CET (N = 51) or an Enriched Supportive Therapy (EST) control (N = 51) and treated for 18 months. Assessments of brain function and structural integrity prior to treatment, at 9 and 18 months will be conducted using magnetic resonance imaging to examine the differential effects of CET on fronto-temporal brain regions previously implicated in neurocognitive and social-cognitive impairments in schizophrenia. In addition, comprehensive data on cognition and functional outcome will be collected to examine the degree to which cognitive and functional improvement during CET is mediated by neurobiologic change. Neuroimaging, cognitive, and functional assessments will also be completed at 1-year post-treatment to examine the durability of CET effects on the brain, cognition, and behavior. Finally, moderator analyses will explore whether a greater pre-treatment neurobiologic reserve is predictive of treatment response, thus allowing the possible personalization of care. Together, this project will result in the first comprehensive characterization of the neurobiologic effects of cognitive rehabilitation in early course schizophrenia, and provide critical information on the neural mechanisms, predictors and durability that are needed to refine and extend current approaches to optimize therapeutic outcomes for early course schizophrenia patients.

描述（由申请人提供）：精神分裂症通常以致残和终生病程为特征，因此必须尽早采取干预措施来改变其有害影响。认知障碍是该疾病最严重的方面之一，也是早期干预的关键目标。我们早期的研究表明，旨在利用现有大脑资源和增强神经可塑性的认知康复方法对于改善早期精神分裂症的认知和功能结果具有重要的前景。认知康复的这些有益效果可能反映了大脑结构和功能完整性的改变。我们从最近完成的认知增强疗法（CET）早期试验中观察到令人兴奋的初步证据，表明早期应用这种新型神经认知和社会认知康复方法可以预防早期精神分裂症的额颞叶灰质损失。然而，除了我们的初步观察之外，人们对认知康复对疾病早期不同功能和结构大脑参数的影响知之甚少。精神分裂症大脑对非药物干预的反应能力具有重要意义，识别早期精神分裂症中认知康复对大脑的影响对于阐明这些方法的神经生物学作用机制、阐明必要的大脑变化至关重要可以支持认知增强，并改进当前的治疗方法。该项目旨在研究 CET 对早期精神分裂症患者大脑功能和结构的影响。疾病早期（病程 < 5 年）的患者将被随机分配至 CET (N = 51) 或强化支持治疗 (EST) 对照组 (N = 51)，并接受 18 个月的治疗。在治疗前、第 9 个月和第 18 个月时，将使用磁共振成像对大脑功能和结构完整性进行评估，以检查 CET 对先前与精神分裂症神经认知和社会认知障碍有关的额颞叶大脑区域的不同影响。此外，还将收集有关认知和功能结果的综合数据，以检查神经生物学变化介导的 CET 期间认知和功能改善的程度。神经影像、认知和功能评估也将在治疗后 1 年完成，以检查 CET 对大脑、认知和行为影响的持久性。最后，调节分析将探讨更大的治疗前神经生物学储备是否可以预测治疗反应，从而允许可能的个性化护理。总之，该项目将首次全面描述早期精神分裂症认知康复的神经生物学效应，并提供有关神经机制、预测因子和持久性的关键信息，这些信息是完善和扩展当前方法以优化早期精神分裂症治疗结果所需的。当然是精神分裂症患者。