Social-Cognitive Rehabilitation and Brain Function in Early Schizophrenia

描述(申请人提供)：精神分裂症是一种严重和持续性的精神障碍，其特征是认知功能严重受损。社会赤字 认知，或处理、解释和调节社会情绪信息的能力，最近被证明是疾病功能恢复的关键限速因素，使它们成为治疗的关键目标。社会认知障碍反映了额颞部大脑功能的假定缺陷，并且对现有的药物干预没有反应。最近，在NIH支持的两项针对精神分裂症患者的临床试验中，一种名为认知增强疗法(CET)的综合认知康复方法被证明能极大地改善社会认知。CET的有益效果可能反映了潜在的大脑功能的变化，当在病程早期应用CET时，可能能够利用神经可塑性储备来改变大脑功能缺陷。事实上，我们最近已经证明，在CET中，社交认知的改善与疾病早期额颞部大脑网络结构完整性的增强有关。然而，除了这些最初的观察之外，人们对社会认知康复对精神分裂症患者大脑功能的神经生物学影响知之甚少。对心理社会干预的神经生物学效应的研究与NIMH确定精神治疗的神经机制的优先目标保持一致，但由于缺乏受过干预和神经科学研究培训的翻译研究人员，此类研究很少在精神分裂症中进行。这项以患者为导向的辅导式职业发展奖(K23)旨在为申请者提供所需的神经科学技能，以连接精神分裂症的心理社会治疗和神经科学研究领域。申请者的长期目标是通过评估心理社会干预对大脑的影响，并开发新的心理社会治疗方法来增强精神分裂症患者的大脑功能，从而促进精神分裂症的治疗。为了实现这一长期目标，已经制定了一个多学科培训计划，为申请者提供以下方面的补充专业知识：(1)神经解剖学和精神分裂症的神经生物学；(2)社会认知和情感神经科学；(3)功能神经成像方法。申请人将在强大的多学科环境中接受神经科学领域资深专家的指导，这将与旨在发展他在翻译神经科学方法和途径方面的专业知识的正式培训和课程作业相结合。一项补充研究计划将对32名早期精神分裂症患者进行一项横断面的治疗后结果研究，研究CET对社会认知脑功能的影响。这项研究计划将首先使用现场标准的情绪知觉功能神经成像范式以及两种新的社会认知范式--观点采择和情绪调节--来表征早期精神分裂症患者(N=16)和匹配的健康对照组(N=16)在社会认知加工过程中大脑功能缺陷的性质。随后，16名在该机构正在进行的临床服务中接受过CET治疗的早期精神分裂症患者将与16名精心匹配的未接触CET的早期患者一起进行研究。使用情绪感知、观点采择和情绪调节范式的治疗后功能神经成像数据将在CET暴露和非CET暴露的患者中收集，以检查干预对额颞脑功能和连接性的影响。总之，这些活动将支持R01申请，以便对CET对社会认知脑功能的影响进行后续的纵向随机试验，并提供所需的独特培训和研究经验，使申请者能够实现其成为精神分裂症患者心理社会治疗对大脑影响的独立调查员的长期目标。这一领域的研究结果有望导致关于精神分裂症大脑可塑性的新发现，确定可以支持社会认知增强的神经机制，并为完善现有的和开发越来越有效的干预措施来治疗这种高度致残的疾病铺平道路。

DESCRIPTION (provided by applicant): Schizophrenia is a severe and persistent psychiatric disorder that is characterized by significant impairments in cognitive function. Deficits in social cognition, or the ability to process, interpret, and regulate socio-emotional information, have been recently shown to be key rate-limiting factors to functional recovery from the illness, making them critical targets for treatment. Social-cognitive impairments reflect a presumed deficit in fronto-temporal brain function, and are unresponsive to extant pharmacologic interventions. Recently, a comprehensive cognitive rehabilitation approach known as Cognitive Enhancement Therapy (CET) has been shown to greatly improve social cognition in two NIH-supported clinical trials with schizophrenia patients. The beneficial effects of CET presumably reflect a change in underlying brain function, and when applied early in the course of illness CET may be able to capitalize on a neuroplasticity reserve to alter functional brain deficits. Indeed, we have recently shown that social-cognitive improvement in CET is associated with an enhanced structural integrity of fronto-temporal brain networks in the early course of the disorder. Beyond these initial observations, however, remarkably little is known about the neurobiologic effects of social-cognitive rehabilitation on brain function in schizophrenia. Research on the neurobiologic effects of psychosocial interventions is aligned with the NIMH priority goal of identifying neural mechanisms of psychiatric treatments, yet such studies have rarely been conducted in schizophrenia due to a lack of translational investigators trained in both intervention and neuroscience research. The purpose of this Mentored Patient-Oriented Career Development Award (K23) is to provide the applicant, a trained social worker and psychosocial interventionist, with the skills in neuroscience needed to bridge the fields of psychosocial treatment and neuroscience research in schizophrenia. The long-term goal of the applicant is to advance the treatment of schizophrenia through evaluating the effects of psychosocial interventions on the brain and developing novel psychosocial treatments to enhance brain function in the disorder. To accomplish this long-term goal, a multidisciplinary training plan has been developed to provide the applicant with complementary expertise in: (1) neuroanatomy and the neurobiology of schizophrenia; (2) social-cognitive and affective neuroscience, and (3) functional neuroimaging methods. The applicant will receive mentoring in a strong multidisciplinary environment from accomplished experts in the field of neuroscience, which will be combined with formal training and coursework designed to develop his expertise in translational neuroscience methods and approaches. A complementary research plan will conduct a cross-sectional, post-treatment outcomes study of the effects of CET on social-cognitive brain function in 32 patients in the early course of schizophrenia. This research plan will proceed by first characterizing the nature of deficits in brain function during social-cognitie processing in early course schizophrenia patients (N = 16) and matched healthy controls (N = 16) using a field standard functional neuroimaging paradigm of emotion perception, along with two novel social cognition paradigms of perspective-taking and emotion regulation. Subsequently, 16 patients in the early course of schizophrenia who have been treated with CET in a ongoing clinical service at the institution will be studied along with 16 carefully matched early course patients who have not been exposed to CET. Post-treatment functional neuroimaging data using the emotion perception, perspective-taking, and emotion regulation paradigms will be collected on both CET-exposed and CET non-exposed patients to examine the effects of the intervention on fronto-temporal brain function and connectivity. Together, these activities will support an R01 application to conduct a subsequent longitudinal randomized trial of CET effects on social-cognitive brain function, and provide the unique training and research experiences needed to enable the applicant to achieve his long-term goal of becoming an independent investigator of the effects psychosocial treatment on the brain in schizophrenia. Results from this area of investigation are expected to lead to new discoveries regarding brain plasticity in schizophrenia, identify the neural mechanisms that can support social-cognitive enhancement, and pave the way for refining existing and developing increasingly effective interventions for this highly disabling condition.