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)： 长期大量饮酒引起的下丘脑-垂体-肾上腺(HPA)内分泌轴可能的紊乱与临床和行为病理有关。(AD)研究报告称，AD患者在酒精戒断过程中皮质醇分泌异常高，地塞米松治疗后白天皮质醇没有受到抑制。其他人发现这种神经内分泌异常在韦尼克-科萨科夫综合征患者中更常见，这表明可能与脑损伤有关。灵长类动物的研究支持这一观点，观察到长期高水平的血清皮质醇与海马区组织的退化有关。注意到之前的研究，我们假设垂体体积的增加和海马体体积的减少将识别出慢性、活跃、重度饮酒者的样本。从MRI扫描获得的体积测量中，我们发现与不饮酒的对照组相比，最近酗酒的一组人的海马体与垂体体积的比率(H：P比率)下降。虽然耐人寻味，但这项研究是在一个方便的样本中进行的。我们现在建议以一种预期的方式进行和扩展这项调查，以确定降低H：P容量比是否起作用 作为AD受试者的状态标记物。如果是，我们问a)这是否表明饮酒的可逆生理后果或永久性的结构变化，以及b)高皮质醇血症导致的H：P比率降低，表明作为一种可能的生理机制，海马体反馈丧失？为了回答这些问题，我们将1)测量30名积极饮酒的AD测试者和30名匹配的非AD对照组受试者的基线H：P体积比率，2)在酒精戒断6个月后连续测量AD受试者的H：P体积比率，以及3)测量两组基线和AD受试者的每日唾液皮质醇分泌。从这项研究中，我们期望开发出有效的、前瞻性收集的数据，开始建立H：P体积比降低的临床和病理生理学意义。我们相信，这项研究最终将为持续酒精暴露引起的大脑功能改变的一个重要方面以及戒酒后神经内分泌功能的恢复提供新的线索。