Multimodal neuroimaging study of relational learning in schizophrenia

描述（由申请人提供）：精神分裂症是一种严重的使人衰弱的精神疾病，折磨着大约1%的人口，是一个严重的公共卫生问题，无法治愈。认知缺陷是该疾病的核心特征，尤其是学习和记忆缺陷。严重的学习记忆障碍患者的社会心理功能和生活质量较差。不幸的是，对于精神分裂症患者的学习和记忆障碍，目前还没有好的治疗方法。因此，有必要更好地了解精神分裂症的学习和记忆失败和成功的神经生物学机制。这些机制是开发新疗法的潜在靶点。提出的研究将使用多模态神经成像方法来调查精神分裂症的关系学习。功能磁共振成像（fMRI）将用于研究精神分裂症患者关系学习过程中的神经激活。扩散张量成像（DTI）和质子磁共振波谱（1H-MRS）将用于帮助确定精神分裂症患者神经激活模式的改变是否与结构白质连接受损或神经化学受损有关。精神分裂症学习表现异质性的神经生物学机制将被表征。第三个目的是通过检查一级亲属来检查精神分裂症患者与关系学习相关的神经生物学改变是否具有遗传影响。这将是首次使用三种神经成像技术来研究精神分裂症患者的关系学习。这些技术的结合有望提供与精神分裂症患者关系学习相关的神经生物学机制的更全面的图景，而不是单独使用任何一种技术。

DESCRIPTION (provided by applicant): Schizophrenia is a severely debilitating psychiatric disorder that afflicts approximately 1% of the population and is a serious public health problem with no cure. Cognitive deficits are a core feature of the illness with learning and memory deficits being particularly disabling. Patients with severe learning and memory impairments have poorer psychosocial function and life quality. Unfortunately, there are no good treatments for learning and memory impairments in schizophrenia. Consequently, there is a need for a better understanding of the neurobiological mechanisms of learning and memory failure and success in schizophrenia. These mechanisms are potential targets for novel treatment development. The proposed study will use multimodal neuroimaging methods to investigate relational learning in schizophrenia. Functional magnetic resonance imaging (fMRI) will be used to investigate neural activation during relational learning in schizophrenia. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS) will be used to help determine whether altered neural activation patterns in schizophrenia are related to compromised structural white matter connections or neurochemistry. The neurobiological mechanisms related to the heterogeneity of learning performance in schizophrenia will be characterized. The third aim is to examine if altered neurobiology associated with relational learning in schizophrenia has a genetic influence by examining first-degree relatives. This will be the first study to use three neuroimaging techniques to investigate relational learning in schizophrenia. The combination of these techniques is expected to provide a more comprehensive picture of altered neurobiological mechanisms associated with relational learning in schizophrenia than any one technique alone. PUBLIC HEALTH RELEVANCE: Schizophrenia is a severely debilitating psychiatric disorder that afflicts approximately 1% of the population and is a serious public health problem. There are no good treatments for learning and memory deficits, core features of the disorder that negatively impact quality of life. This study will use three neuroimaging techniques to investigate neural activation patterns, white matter circuitry, and neurochemistry associated with relational learning in schizophrenia. It is predicted that the integration of these measurements will serve as targets for the development of novel drug and behavioral treatment for learning and memory deficits in schizophrenia.