DEBRISOQUIN AS AN AGENT FOR STUDY OF PSYCHOTIC STATES

精神分裂症/精神病患者和对照组将进行交叉研究。 横断面和纵向设计评价去甲肾上腺素能 这些患者的活跃度增加。去甲肾上腺素的代谢物 具体研究对象为VMA、去甲肾上腺素和MHPG。我们还将 看看脑脊液中去甲肾上腺素和代谢物的水平。的运作 多巴胺系统将通过测量尿液中的HVA和DOPAC进行评估， 血浆和脑脊液。一般的假设是去甲肾上腺素能系统 精神分裂症受试者的多动症和精神分裂症/精神病 以去甲肾上腺素和/或其水平升高为特征 所有体液中的代谢物，而且还增加了 血浆HVA不增加总多巴胺合成(尿HVA)。 神经递质代谢产物将在患者断断续续的情况下进行研究 去溴异喹(DBQ)和在治疗期间使用任何一种神经抗精神病药 (氟哌啶醇)或α2激动剂可乐定。我们将按原来的方式使用DBQ 单胺氧化酶抑制活性，但不能穿透大脑。通过 减少脑内DA和NE代谢物的外周贡献 尿液和血浆它的使用会导致多巴胺的代谢产物，可能 血浆和尿液中的去甲肾上腺素更好地反映了 中枢神经系统中胺代谢物的浓度低于 没有药物的话。DBQ的这种用法在我们以前的版本中已被证明非常有价值 学习。这项工作的长期目标是理解 精神分裂症/精神病中的NE系统，并将这一知识应用于 改进治疗方案的设计。建议使用DBQ进行的工作是 继续和延长我们的研究计划，这可能会产生 有关当前和未来诊断和治疗的临床有用信息 精神分裂症患者的治疗努力。

Schizophrenic/psychotic patients and controls will be studied in a cross sectional and longitudinal design to evaluate whether noradrenergic activity is increased in these patients. The metabolites of norepinephrine specifically to be studied are VMA, normetanephrine and MHPG. We will also look at levels of norepinephrine and metabolites in CSF. The functioning of the dopamine system will be assessed by measuring HVA and DOPAC in urine, plasma and CSF. The general hypotheses are that noradrenergic systems are hyperactive in schizophrenic subjects and that schizophrenia/psychosis is characterized by an increased level of norepinephrine and/or its metabolites in all body fluids and that there is also an increased level of plasma HVA without an increase in total DA synthesis (urine HVA). Neurotransmitter metabolites will be studied with patients on and off debrisoquin (DBQ) and during treatment with either neuroleptics (haloperidol) or the alpha2 agonist clonidine. We will use DBQ as it has monoamine oxidase inhibiting activity but does not penetrate brain. By reducing the peripheral contribution of metabolites of DA and NE present in urine and plasma its use results in the metabolites of dopamine and perhaps norepinephrine in plasma and urine better reflecting the activity and concentrations of amine metabolites in the central nervous system than without the drug. This use of DBQ has proven quite valuable in our prior studies. The long-term goal of this work is to understand the role of the NE system in schizophrenia/psychosis and to apply this knowledge to the design of improved treatments. This proposed work with DBQ is a continuation and extension of our program of research that may yield clinically useful information regarding present and future diagnostic and treatment efforts with schizophrenic patients.