Biomarker for Cognitive Impairment in Chronic Schizophrenia

慢性精神分裂症认知障碍的生物标志物

基本信息

批准号：
7611914
负责人：
Richard James McClure
金额：
$ 18.72万
依托单位：
PHFR, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7611914
关键词：
Alcoholism Basal Ganglia Bayesian Method Bilateral Biological Markers Brain Brain imaging Brain region Cell physiology Chronic Chronic Disease Chronic Schizophrenia Clinical Code Cognition Cognitive deficits Color Computer software Creatine Data Data Analyses Data Set Disease Evaluation Female Funding Future Gangliosides Glutamates Goals Government High Prevalence Impaired cognition Impairment Individual Inferior Lead Left Life Magnetic Resonance Spectroscopy Measures Membrane Metabolic Metabolism Methods Molecular Monitor Morbidity - disease rate N-acetylaspartate N-acetylaspartylglutamate National Institute on Alcohol Abuse and Alcoholism Nerve Degeneration Neurobiology Neurocognition Neurons Neuropsychological Tests Nicotine Occipital lobe Outcome Parietal Lobe Patients Persons Phase Phosphocreatine Phospholipid Metabolism Phospholipids Pilot Projects Population Control Prefrontal Cortex Recording of previous events Risk Schizophrenia Sensitivity and Specificity Small Business Technology Transfer Research Smoke Smoker Smoking Specificity Statistical Methods Structure Subgroup Symptoms Synapses Temporal Lobe Testing Text Therapeutic Time Training United States National Institutes of Health Work base cognitive change design in vivo inorganic phosphate insight magnetic resonance spectroscopic imaging male middle age neuron loss neuropsychiatry neuropsychological non-smoker novel phosphodiester phosphomonoester prevent public health relevance relating to nervous system repaired response sugar

项目摘要

DESCRIPTION (provided by applicant): This application focuses on developing a novel brain molecular biomarker for cognitive impairment in chronic schizophrenia. Previous work has suggested a subgroup of chronic schizophrenia with severe, generalized cognitive impairment, a very poor outcome, predominance of negative, or "deficit," symptoms, and a history of unremitting, chronic illness. The neurobiological basis for the cognitive impairment and poor outcome in this subgroup of schizophrenia is unknown. What is critically lacking is a brain molecular biomarker that antedates both the cognitive impairment and the earliest, most minimal brain structural changes. Given the increased morbidity associated with cognitive impairment in chronic schizophrenia subjects, further insights into the molecular basis for the cognitive changes are essential and could lead to future therapeutic and preventative measures as well as the ability to monitor neuromolecular responses to these therapeutic measures. The purpose of the present Phase 1 STTR application is to analyze existing NIH-funded multi- voxel 31P and 1H magnetic resonance spectroscopic imaging data sets to develop a brain molecular biomarker for the cognitive impairment observed in some chronic schizophrenia subjects. The neuromolecular biomarker will reflect molecular changes that antecede brain structural changes observed by quantitative MRI-based neuromorphometrics and will predict which subjects with chronic schizophrenia are at increased risk to develop cognitive impairment. The proposed approach is unique because it directly and non-invasively measures critical aspects of brain molecular composition and metabolism in living subjects, including key aspects of membrane phospholipid metabolism, utilization of high-energy phosphates, and a marker of neuronal integrity. Since cognitive deficits are present in other neuropsychiatric disorders, for example chronic alcoholism, a comparison of molecular measures associated with cognitive impairment in chronic alcoholism with those of chronic schizophrenia will help to establish the specificity of the biomarker for cognitive impairment in schizophrenia. A brain molecular biomarker which could distinguish molecular findings associated with cognitive impairment in chronic schizophrenia from that observed in other neuropsychiatric disorders would be of great theoretical and practical clinical importance. PUBLIC HEALTH RELEVANCE: A brain molecular biomarker such as proposed in this application could be used to guide further understanding of the molecular underpinnings of cognitive impairment in chronic schizophrenia. This will enhance future therapeutic and preventative approaches designed to repair or prevent neural membrane damage observed in schizophrenia. The molecular biomarker will be used to develop a software package that will analyze individual 31P and 1H magnetic resonance spectroscopic imaging data and produce a color-coded brain image showing how that subject compares to a control population.

描述（由申请人提供）：本申请专注于开发一种新型的脑分子生物标志物，以用于慢性精神分裂症的认知障碍。先前的工作表明，具有严重，普遍认知障碍的慢性精神分裂症亚组，结果非常差，负面或“赤字”，症状，症状以及无所不在的慢性病病史。精神分裂症亚组中认知障碍和结果不佳的神经生物学基础尚不清楚。批判性缺乏的是一种脑分子生物标志物，它既可以抗认知障碍，又是最早，最小的大脑结构变化。鉴于与慢性精神分裂症受试者认知障碍相关的发病率增加，对认知变化的分子基础的进一步见解至关重要，并且可能导致未来的治疗和预防措施以及监测对这些治疗方法的神经分子反应的能力。本第1阶段应用程序的目的是分析现有的NIH资助的多素体31p和1H磁共振光谱成像数据集，以开发一些在一些慢性精神分裂症患者中观察到的认知障碍的脑分子生物标志物。神经分子生物标志物将反映通过基于定量MRI的神经形态图观察到的脑结构变化的分子变化，并将预测哪些患有慢性精神分裂症的受试者有增加认知障碍的风险。该方法是独一无二的，因为它直接和非侵入性测量了生物中脑分子组成和代谢的关键方面，包括膜磷脂代谢的关键方面，高能磷酸盐的利用以及神经元完整性的标志。由于认知缺陷存在于其他神经精神疾病中，例如慢性酒精中毒，因此比较了与慢性酒精中毒的认知障碍与慢性精神分裂症的分子措施的比较，将有助于确定精神分裂症认知障碍的生物标志物的特异性。一种可以区分与慢性精神分裂症认知障碍相关的分子发现与在其他神经精神疾病中观察到的分子发现的大脑分子生物标志物将具有很大的理论和实际临床重要性。公共卫生相关性：本应用中提出的脑分子生物标志物可以用于指导对慢性精神分裂症认知障碍的分子基础的进一步理解。这将增强未来的治疗方法和预防方法，旨在修复或预防精神分裂症中观察到的神经膜损害。分子生物标志物将用于开发一个软件包，该软件包将分析单个31p和1H磁共振光谱成像数据并产生颜色编码的大脑图像，以表明该受试者与对照人群相比的比较。