Hippocampus /Pituitary Ratio and Alcohol Dependence

海马/垂体比率和酒精依赖

• 批准号: 6570024
• 负责人: THOMAS P BERESFORD
• 金额: $ 12.48万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-05 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6570024
• 关键词: adult human (21+); alcoholic beverage consumption; alcoholism /alcohol abuse; brain imaging /visualization /scanning; brain injury; brain morphology; clinical research; cortisol; hippocampus; human subject; hypercortisolism; hypothalamic pituitary axis; immunologic assay /test; longitudinal human study; magnetic resonance imaging; male; neural information processing; patient oriented research; pituitary gland; psychopathology

DESCRIPTION (provided by applicant): Possible disorders of the hypothalamic-pituitary-adrenal (HPA) endocrine axis have been implicated in both clinical and behavioral pathology resulting from the prolonged, heavy drinking of Alcohol Dependence. (AD) Studies report abnormally high levels of cortisol secretion during ethanol withdrawal as well as non-suppression of diurnal cortisol after dexamethasone in AD sufferers. Others found such neuro-endocrine abnormalities more frequently among Wernicke-Korsakoff Syndrome cases, suggesting a possible relation to brain injury. Studies from primates support this, observing chronically high levels of serum cortisol associated with degeneration of the hippocampal tissue. Noting previous research, we hypothesized that an increase in pituitary volume and a reduction in hippocampal volume would identify a sample of chronic, active, heavy drinkers. From volume measurements acquired by MRI scanning, we found that a decreased ratio of the hippocampus-to-pituitary volume (H:P ratio) characterized a group of recent, heavy drinkers as compared to a non-drinking control group. Although intriguing, this study was done in a convenience sample. We now propose to perform and extend this inquiry in a prospective fashion in order to establish whether a reduced H:P volume ratio serves as a state marker among AD subjects. If so, we ask a) does this indicate a reversible physiologic consequence of drinking or permanent structural change, and b) is reduced H:P ratio associated with hypercortisolemia, indicating loss of hippocampal feedback as a possible physiologic mechanism? To answer these questions, we will 1) measure baseline H:P volume ratios in 30, actively drinking, AD test subjects and in 30 matched, non-heavy drinking, non-AD control subjects, 2) measure H:P volume ratios serially in AD subjects after six months of ethanol abstinence, and 3) measure diurnal salivary cortisol secretion at baseline for both groups and serially for AD subjects. From this study we expect to develop valid, prospectively gathered, data that can begin to establish the clinical and patho-physiologic meaning of the decrease in the H:P volume ratio. We believe this line of investigation will ultimately shed new light on an important aspect of altered brain function due to sustained ethanol exposure as well as recovery of neuroendocrine functioning after cessation of heavy alcohol use.

描述（由申请人提供）： 下丘脑 - 垂体 - 肾上腺（HPA）内分泌轴的可能疾病与临床和行为病理有关，这是由于延长，大量饮酒依赖性而导致的。 （AD）研究报告说，在AD患者中地塞米松后，乙醇戒断期间的皮质醇分泌异常高以及昼夜皮质醇的不抑制。其他人则发现，在Wernicke-Korsakoff综合征病例中，这种神经内分泌异常更频繁，这表明可能与脑损伤有关系。灵长类动物的研究支持这一点，观察到与海马组织退化有关的长期高水平的血清皮质醇。我们指出，我们假设垂体量的增加和海马体积减少将确定慢性，活跃，重型饮酒者的样本。根据MRI扫描获得的体积测量值，我们发现与非饮用的对照组相比，海马与垂体体积（H：P比）的比例降低，其最新饮用者的比例降低了。尽管很有趣，但这项研究是在便利样本中进行的。现在，我们建议以潜在的方式进行和扩展此询问，以确定降低的H：P体积比是否有效 作为广告主题中的国家标记。如果是这样，我们要求a）这是否表明饮酒或永久性结构变化的可逆生理后果，b）降低了与高皮层血症相关的H：P比，表明海马反馈的丧失是可能的生理机制？ 要回答这些问题，我们将1）测量基线h：30中的p量比，积极饮酒，AD测试对象以及30个匹配的，非繁殖的饮酒，非AD对照对象，2）测量H：P体积比在六个月后乙醇弃酚的AD主题和3）在基本的基准和基线的AD基准和均为AD的AD基准均为AD和sermine Ads erserme as AD AD均为AD。从这项研究中，我们期望开发有效的，前瞻性收集的数据，这些数据可以开始建立H：P体积比的降低的临床和病态生理意义。我们认为，由于持续的乙醇暴露以及停止大量饮酒后的神经内分泌功能，这种调查最终将为改变大脑功能的重要方面提供新的启示。