Hippocampus/Pituitary Ratio: an AD Brain Injury Marker?

海马/垂体比率：AD 脑损伤标志物？

• 批准号: 6732059
• 负责人: THOMAS P BERESFORD
• 金额: $ 12.6万
• 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/6732059
• 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) 内分泌轴可能出现的紊乱与长期大量饮酒造成的临床和行为病理学有关。 (AD) 研究报告称，AD 患者在戒酒期间皮质醇分泌水平异常高，并且在使用地塞米松后，昼间皮质醇分泌未受到抑制。其他人发现这种神经内分泌异常在韦尼克-科萨科夫综合症病例中更为常见，这表明可能与脑损伤有关。灵长类动物的研究支持了这一点，观察到长期高水平的血清皮质醇与海马组织的退化有关。根据之前的研究，我们假设垂体体积的增加和海马体体积的减少可以识别出慢性、活跃、重度饮酒者的样本。根据 MRI 扫描获得的体积测量结果，我们发现，与不饮酒的对照组相比，近期酗酒者的海马体与垂体体积之比（H:P 比）下降。尽管很有趣，但这项研究是在方便样本中进行的。我们现在建议以前瞻性的方式进行和扩展这项调查，以确定降低 H:P 体积比是否有效 作为 AD 受试者中的状态标记。如果是这样，我们会问：a）这是否表明饮酒或永久性结构变化的可逆生理后果，b）与高皮质醇血症相关的 H:P 比值降低，表明海马反馈的丧失是一种可能的生理机制？ 为了回答这些问题，我们将 1) 测量 30 名活跃饮酒的 AD 测试受试者和 30 名匹配的非重度饮酒的非 AD 对照受试者的基线 H:P 体积比，2) 在戒酒六个月后连续测量 AD 受试者的 H:P 体积比，以及 3) 在基线时测量两组和连续的 AD 受试者的每日唾液皮质醇分泌量。从这项研究中，我们期望开发出有效的、前瞻性收集的数据，这些数据可以开始确定 H:P 体积比下降的临床和病理生理意义。我们相信，这一系列的研究最终将揭示由于持续乙醇暴露而导致的大脑功能改变的一个重要方面，以及停止大量饮酒后神经内分泌功能的恢复。