Biomarker of Cognitive Impairment in Chronic Alcoholism

慢性酒精中毒认知障碍的生物标志物

• 批准号: 7102960
• 负责人: Samuel Gershon
• 金额: $ 10.04万
• 依托单位: PHFR, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102960
• 关键词: alcoholism /alcohol abuse; basal ganglia; behavioral /social science research tag; biomarker; biomaterial development /preparation; brain imaging /visualization /scanning; clinical research; cognition disorders; drug addiction; human data; lipid metabolism; metabolomics; nicotine; parietal lobe /cortex; phospholipids; psychopharmacology; schizophrenia; smoking; statistics /biometry; substance abuse related behavior; temporal lobe /cortex

DESCRIPTION (provided by applicant): This Phase I, STTR application focuses on developing a novel brain molecular metabolomic biomarker for cognitive impairment in chronic alcoholism. Approximately 1 1/2 to 2/3rds of recently detoxified chronic alcoholics have cognitive impairment. The molecular underpinnings for the cognitive impairment and why some chronic alcoholics became cognitively impaired and not others is unknown. At a molecular level, ethanol has been shown to have both acute and chronic effects on membrane associated function and properties. The purpose of the present application is to analyze existing NIHfunded multi-voxel 31P and 1H magnetic resonance spectroscopic imaging (31P-1H MRSI) data sets to develop a brain molecular biomarker for the Cognitive impairment observed in some chronic alcoholism subjects. Since cognitive deficits are present in other neuropsychiatric disorders, for example chronic schizophrenia, a comparison of molecular measures associated with cognitive impairment in chronic schizophrenia with those of chronic alcoholism will help to establish a biomarker specific for cognitive impairment in alcoholism. Since the majority of alcoholics smoke, the effect of nicotine on the MRSI measures will be provided by a (NIH-funded) nicotine challenge to middle age smokers which will be included in the analysis. Funds are requested for Phfr, Inc., a small business focused on the development and commercialization of novel, non-invasive brain imaging biomarkers for neuropsychiatric disorders such as chronic alcoholism, Alzheimer's disease, major-depressive disease, and schizophrenia with the University of Pittsburgh as the nonprofit partner. In Phase I, we propose to analyze 31P-1H data from: a pilot study of cognition in chronic alcoholism (males, cognitively impaired N=4; cognitively unimpaired N=5; control subjects N=16); an NIH funded study (MH058308) of cognition in chronic schizophrenia (males, cognitively impaired N=19; cognitively unimpaired N=16; control subjects N=10); and an NIH funded study (DA11735) of the effect of nicotine (smokers, males N=4, females N=4). The data from these in vivo multi-voxel 31P-1H MRSI studies provide measures of molecular alterations in brain membrane phospholipid and high-energy phosphate metabolism, synaptic/transport vesicles and phosphorylated proteins and metabolites with N-acetyl moieties from right and left prefrontal, superior temporal, inferior parietal, occipital, basal ganglia, and centrum semiovale brain regions. The brain molecular biomarker will provide insights into the molecular basis for cognitive impairment in chronic alcoholism which could lead to future therapeutic and preventative measures.

描述（由申请人提供）：该第一阶段 STTR 申请重点开发一种新型脑分子代谢组生物标志物，用于治疗慢性酒精中毒的认知障碍。大约 1 1/2 至 2/3 最近戒毒的慢性酗酒者患有认知障碍。认知障碍的分子基础以及为什么一些慢性酗酒者会出现认知障碍而其他人则不会的原因尚不清楚。在分子水平上，乙醇已被证明对膜相关功能和特性具有急性和慢性影响。本申请的目的是分析现有的 NIH 资助的多体素 31P 和 1H 磁共振波谱成像 (31P-1H MRSI) 数据集，以开发针对在一些慢性酒精中毒受试者中观察到的认知障碍的脑分子生物标志物。由于认知缺陷也存在于其他神经精神疾病中，例如慢性精神分裂症，因此将慢性精神分裂症认知障碍与慢性酒精中毒认知障碍相关的分子测量结果进行比较，将有助于建立针对酒精中毒认知障碍的特异性生物标志物。由于大多数酗酒者吸烟，尼古丁对 MRSI 测量值的影响将通过（NIH 资助的）对中年吸烟者的尼古丁挑战来提供，该挑战将包含在分析中。 Phfr, Inc. 是一家小型企业，专注于与匹兹堡大学合作开发和商业化新型非侵入性脑成像生物标志物，用于治疗慢性酒精中毒、阿尔茨海默病、重度抑郁症和精神分裂症等神经精神疾病。作为非营利合作伙伴。在第一阶段，我们建议分析来自以下各项的 31P-1H 数据： 慢性酒精中毒认知的初步研究（男性，认知受损 N=4；认知未受损 N=5；对照受试者 N=16）；一项 NIH 资助的慢性精神分裂症认知研究 (MH058308)（男性，认知受损 N=19；认知未受损 N=16；对照受试者 N=10）； NIH 资助的一项关于尼古丁影响的研究 (DA11735)（吸烟者，男性 N=4，女性 N=4）。这些体内多体素 31P-1H MRSI 研究的数据提供了脑膜磷脂和高能磷酸盐代谢、突触/运输囊泡以及磷酸化蛋白质和来自左右前额叶的 N-乙酰基部分的代谢物的分子改变的测量，颞上叶、顶下叶、枕叶、基底神经节和半卵圆中心脑区。大脑分子生物标志物将为慢性酒精中毒认知障碍的分子基础提供见解，这可能会导致未来的治疗和预防措施。