MONOAMINE RECEPTOR SENSITIVITY AND MENTAL ILLNESS

有研究表明，情感性疾病中的生物胺功能障碍 精神分裂症可能是单胺改变的结果 这些患者的中枢神经系统中的受体敏感性。 尽管动物提供了一些证据来支持这一建议， 然而，缺乏人类研究的证据。 最近两 β-肾上腺素能受体敏感性的初步研究得出结论， 这种单胺受体功能的改变存在于 抑郁症患者 本项目研究单胺受体的作用 精神疾病的病因学以及 对精神药物的治疗反应和单胺 受体敏感性 外周组织单胺受体的研究 这些精神分裂症、抑郁症和躁狂症患者和正常对照组 是（1）α-肾上腺素能（α-2）和5-羟色胺1和2受体和（2） 白细胞中的β肾上腺素能和组胺-2受体。 受体 将通过测定3 H-环的改变来检查灵敏度（1） 由于这些受体的刺激导致AMP蓄积和/或（2） 通过用放射性测定这些受体的动力学特性， 标记的配体结合技术（结合位点的最大数目， 解离常数）。 该项目的第一部分将比较 这些受体在不同诊断中的特性（例如， 亚组DSM III精神分裂症，分裂样精神病簇， 单相抑郁症、双相抑郁症、双相躁狂症）和正常 对照以确定一种或多种单胺的改变是否 受体敏感性与这些诊断中的一个或几个相关。 分组。 该项目的第二部分将审查是否治疗与 精神药物引起单胺受体敏感性的变化， 这些变化是否与这些药物的临床反应有关， 毒品 该项目的目的是检验所提出的假设， 单胺受体敏感性的改变可能与AT 至少是一些情感疾病和精神分裂症。

It has been suggested that biogenic amine dysfunction in affective illness and schizophrenia may be the result of alterations in the monoamine receptor sensitivity in the central nervous system of these patients. Although some evidence to support this suggestion is provided by animal studies, evidence from human studies has been lacking. Recently two preliminary studies of beta-adrenergic receptor sensitivity conclude that such alterations in monoamine receptor function exist in the leukocytes of depressed patients. This project examines the role of monoamine receptors in the etiology of psychiatric illness and the relationship between therapeutic response to psychotropic drugs and alterations in monoamine receptor sensitivity. The monoamine receptors studied in peripheral tissue of these schizophrenic, depressed, and manic patients and normal controls are (1) alpha-adrenergic (Alpha-2) and serotonin 1 & 2 receptors and (2) beta adrenergic and histamine-2 receptors in leukocytes. The receptor sensitivity will be examined (1) by determining alterations in 3H-cyclic AMP accumulation as a result of stimulation of these receptors and/or (2) by determining the kinetic characteristics of these receptors with radio labelled ligand binding techniques (maximum number of binding sites, disassociation constant). The first part of the project will compare characteristics of these receptors among different diagnostic (e.g., subgroups DSM III schizophrenics, schizophreniform psychosis cluster, unipolar depression, bipolar-depression, bipolar mania), and normal controls to determine if alterations in one or more of the monoamine receptor sensitivity are associated with one or several of these diagnostic subgroups. The second part of the project will examine if treatment with psychotropic drugs causes changes in monoamine receptor sensitivity and whether or not such changes are related to clinical response to these drugs. The project is intended to examine the proposed hypothesis that alterations in monoamine receptor sensitivity may be associated with at least some forms of affective illness and schizophrenia.