GABA deficit hypothesis of impaired visual inhibition in schizophrenia

精神分裂症视觉抑制受损的 GABA 缺陷假说

• 批准号: 8150377
• 负责人: JONG H YOON
• 金额: $ 19.01万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-28 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8150377
• 关键词: Address; Biological Markers; Biological Models; Brain; Cognition; Cognitive; Cognitive deficits; Complex; Control Groups; Development; Disease; Disease Marker; Experimental Designs; Experimental Models; Future; Goals; Influentials; Lateral; Lead; Magnetic Resonance Spectroscopy; Maps; Measures; Mediating; Methods; Modeling; Molecular Genetics; Neocortex; Neural Pathways; Neuroanatomy; Neurobiology; Pathway interactions; Perception; Play; Process; Psychophysiology; Public Health; Refractory; Role; Schizophrenia; Series; Source; Symptoms; Testing; Visual; Visual Cortex; Visual Psychophysics; Visual system structure; Work; base; cohort; disability; first episode schizophrenia; gamma-Aminobutyric Acid; in vivo; indexing; information processing; neurobiological mechanism; neuromechanism; neurotransmission; novel; public health relevance; relating to nervous system; research study; severe mental illness; visual process; visual processing

DESCRIPTION (provided by applicant): Cognitive deficits are now recognized as a significant source of disability in schizophrenia, which is a common, debilitating illness. Currently available treatments have, at best, modest effects on cognitive deficits. This situation calls for the elucidation of the neural mechanisms responsible for the cognitive deficits so that novel treatments can be developed. Given the complexity of schizophrenia, this goal requires first the identification of a specific impaired cognitive process so that it can be mapped onto specific underlying neural pathways and processes. These goals have proven very difficult due to the presence of generalized deficits and the complexity of some of the most notable cognitive deficits in schizophrenia. This project addresses these challenges by focusing on a relatively simple information process pathway whose functional neuroanatomy is relatively well known. We will apply the sophisticated experimental designs and methods utilized in visual psychophysics to control for generalized deficits and to identify a specific deficit in cognitive inhibition in visual processing. We will combine this approach with magnetic resonance spectroscopy to test the hypothesis of an association between GABA deficiency and cognitive inhibition of visual processing in schizophrenia. The successful completion of this project will represent the first in a series of studies that will eventually lead to one of the first demonstrations of a neural mechanism of an impaired cognitive process in schizophrenia. This work promises to yield potential disease biomarkers and a micro-circuit level model of information processing deficits. This model system will facilitate future genetics, molecular and cellular studies relevant to the full understanding of the neurobiological bases of cognitive deficits in schizophrenia, and to the development of new treatments targeting them. PUBLIC HEALTH RELEVANCE: The cognitive deficits in schizophrenia represent a tremendous public health burden yet we still know very little about their neural bases. This project will study the neural mechanism of a specific information processing pathway impaired in schizophrenia by testing the hypothesis that deficiencies in GABA is associated with abnormalities in visual inhibition. This and related future studies will lead to one of the first demonstrations of a neural mechanism of cognitive deficits in schizophrenia and may lead to the identification of new biomarkers and the development of targeted therapies for cognitive deficits in schizophrenia.

描述（由申请人提供）：认知缺陷现在被认为是精神分裂症残疾的重要来源，精神分裂症是一种常见的使人衰弱的疾病。目前可用的治疗方法充其量对认知缺陷有适度的影响。这种情况要求阐明负责认知缺陷的神经机制，以便可以开发新的治疗方法。鉴于精神分裂症的复杂性，这一目标首先需要识别特定的受损认知过程，以便将其映射到特定的潜在神经通路和过程。这些目标已被证明是非常困难的，由于存在广泛的缺陷和复杂的一些最显着的认知缺陷的精神分裂症。这个项目通过关注一个相对简单的信息处理途径来解决这些挑战，其功能神经解剖学相对较为人所知。我们将应用复杂的实验设计和视觉心理物理学中使用的方法来控制广义缺陷，并确定在视觉处理中认知抑制的特定缺陷。我们将联合收割机这种方法与磁共振波谱测试的GABA缺乏症和认知抑制的视觉处理精神分裂症之间的关联的假设。该项目的成功完成将代表一系列研究中的第一个，这些研究最终将导致首次证明精神分裂症认知过程受损的神经机制之一。这项工作有望产生潜在的疾病生物标志物和信息处理缺陷的微电路水平模型。该模型系统将促进未来的遗传学，分子和细胞研究有关的精神分裂症认知缺陷的神经生物学基础的充分理解，并针对他们的新的治疗方法的发展。 公共卫生相关性：精神分裂症的认知缺陷是一个巨大的公共卫生负担，但我们仍然对他们的神经基础知之甚少。本项目将通过验证GABA缺乏与视觉抑制异常相关的假设，研究精神分裂症中特定信息处理通路受损的神经机制。这项研究和相关的未来研究将导致精神分裂症认知缺陷的神经机制的首次演示之一，并可能导致新的生物标志物的识别和精神分裂症认知缺陷的靶向治疗的发展。