Brain Imaging, Cognitive Enhancement and Early Schizophrenia

描述（由申请人提供）：精神分裂症的特点往往是致残和终身病程，因此必须尽早采取干预措施，以改变其有害影响。认知障碍是疾病最致残的方面之一，是早期干预的关键目标。我们早期的研究表明，旨在利用现有的大脑资源和增强神经可塑性的认知康复方法，对改善早期精神分裂症的认知和功能结果表现出显着的承诺。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。我们已经观察到令人兴奋的初步证据，从我们最近完成的早期课程试验的认知增强疗法（CET）表明，这种新的神经认知和社会认知康复方法的早期应用可以防止额颞灰质损失在早期病程精神分裂症。然而，除了我们的初步观察之外，关于认知康复对疾病早期各种功能和结构脑参数的影响，我们知之甚少。精神分裂症大脑对非药物干预的反应能力具有重要意义，并且确定认知康复对早期精神分裂症大脑的影响对于阐明这些方法的神经生物学作用机制，澄清可以支持认知增强的必要大脑变化以及改进当前治疗至关重要。本研究拟探讨CET对早期精神分裂症患者脑功能和结构的影响。处于疾病早期过程（疾病持续时间< 5年）的患者将被随机分配到CET（N = 51）或强化支持疗法（EST）对照组（N = 51），并治疗18个月。在治疗前、第9个月和第18个月时，将使用磁共振成像对脑功能和结构完整性进行评估，以检查CET对先前涉及精神分裂症神经认知和社会认知障碍的额颞脑区域的不同影响。此外，将收集有关认知和功能结局的综合数据，以检查CET期间认知和功能改善由神经生物学变化介导的程度。还将在治疗后1年完成神经影像学、认知和功能评估，以检查CET对大脑、认知和行为影响的持久性。最后，主持人分析将探讨是否更大的治疗前神经生物储备是治疗反应的预测，从而允许可能的个性化护理。总之，该项目将导致认知康复对早期精神分裂症的神经生物学效应的第一次全面表征，并提供有关神经机制，预测因子和耐久性的关键信息，这些信息需要改进和扩展当前的方法以优化早期精神分裂症患者的治疗结果。

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.