OUTPATIENT CLINIC FOR GENETIC AND PHARMACOLOGIC STUDIES OF AFFECTIVE DISORDERS

情感障碍遗传和药理学研究门诊

• 批准号: 3944613
• 负责人: W H BERRETTINI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3944613
• 关键词: Alzheimer's disease; REM sleep; adolescence (12-20); adrenocorticotropic hormone; anorexia; cerebrospinal fluid; clonidine; computed axial tomography; disease /disorder proneness /risk; genetic markers; human population genetics; human subject; human therapy evaluation; melatonin; neurophysiology; neurotransmitter metabolism; nutrition related tag; physostigmine; psychopharmacology; twin /multiplet

The high-risk study of healthy adolescent offspring of bipolar parents has identified a potential vulnerability marker in the at- risk population. The high-risk group shows supersensitivity to the inhibitory effects of light on plasma melatonin, suggesting that this finding may represent a genetic vulnerability marker for affective disorder. We have completed a study of cholinergic induction of rapid eye movement (REM) sleep in euthymic unmedicated bipolars. The bipolars showed more rapid induction of REM sleep than did matched controls, confirming previous observations and providing additional evidence that cholinergic supersensitivity may be a genetic vulnerability marker for affective disorder. Studies of the growth hormone response to clonidine in euthymic unmediated bipolars suggest that this response is blunted in bipolar subjects compared to controls. The possibility that this represents a genetic vulnerability marker is currently being evaluated. Studies of CSF neuropeptides in normal monozygotic and dizygotic twins have shown that neuropeptide Y levels are heritable, are high in underweight anorectics and are normal in depressives. Additionally, the related neuropeptide, peptide YY, is elevated in CSF from bulimic subjects. Galanin levels in CSF are normal in Alzheimer's Disease, depression and eating disorders. Acute IV administration of physostigmine produces increases in CSF neuropeptide Y, in both monkeys and man, indicating that pharmacologic challenges may employ CSF neuropeptide levels in assessing the drug effect on various CNS neurotransmitters.

健康青少年后代的高风险研究 父母已经确定了AT-的潜在脆弱性标记 风险人口。 高风险组显示出对 光对血浆褪黑激素的抑制作用，表明 这一发现可能代表一个遗传脆弱性标记 情感障碍。 我们已经完成了快速眼胆碱能诱导的研究 运动（REM）睡在正式的未药物双皮拉中。 这 双曲线显示出比以下情况更快的REM睡眠诱导 匹配的控件，确认先前的观察并提供 其他证据表明胆碱能超敏反应可能是 情感障碍的遗传脆弱性标记。 研究生长激素对可乐定在整齐于肌酸的反应的研究 未介导的双皮拉表明，这种反应在 与对照组相比，双极受试者。 这可能性 代表目前正在的遗传脆弱性标记 评估。 在正常单锌和 双胞胎双胞胎已经表明神经肽y水平是 可遗传的，体重不足的厌食症，很正常 抑郁症。 另外，相关的神经肽，肽yy， 来自Bulimic受试者的CSF中升高。 CSF中的加拉宁水平 在阿尔茨海默氏病，抑郁和饮食中是正常的 疾病。 急性静脉注射物理学的施用会增加 猴子和人的CSF神经肽Y，表明 药理挑战可能在 评估药物对各种CNS神经递质的影响。