Hsiao J K, Potter W Z, Agren H, Owen R R, Pickar D
Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892.
Psychopharmacology (Berl). 1993;112(1 Suppl):S76-84. doi: 10.1007/BF02245010.
Monoamine neurotransmitter systems are widely thought to be involved in the pathophysiology of affective disorders and schizophrenia and the mechanism of action of antidepressant and antipsychotic drugs. Previous clinical studies have focused on individual monoamine function in isolation, even though a large number of preclinical studies have demonstrated that monoamine neurotransmitter systems interact with one another. In the present paper, preclinical data on monoamine neurotransmitter interactions are reviewed, and two methods for examining monoamine neurotransmitter system interactions in clinical data are presented. One of the best replicated findings in biological psychiatry is that monoamine metabolites in CSF correlate with one another. The degree of correlation may be in part a measure of the degree of interaction between the parent monoamine neurotransmitter systems. Another approach to studying interactions is the use of HVA/5HIAA and HVA/MHPG ratios as an index of interactions between 5HT-DA and NE-DA. When these methods are applied in schizophrenia, patients are found to have decreased monoamine metabolite correlations compared to normal controls. Metabolite correlations increase significantly after antipsychotic treatment, and the HVA/5HIAA and HVA/MPHG ratios also increase, suggesting that neuroleptics may act in part by strengthening interactions between monoamines. BPRS ratings are negatively correlated with HVA/5HIAA and HVA/MHPG so that patients with higher ratios have fewer symptoms, particularly after treatment. These results provide direct experimental support for hypotheses suggesting that interactions between monoamine neurotransmitters are important in schizophrenia. Some of the effects of the atypical neuroleptic, clozapine, on metabolite correlations and ratios are also discussed.
人们普遍认为，单胺神经递质系统参与情感障碍和精神分裂症的病理生理学过程以及抗抑郁药和抗精神病药的作用机制。以往的临床研究一直孤立地关注单个单胺的功能，尽管大量临床前研究表明单胺神经递质系统之间会相互作用。在本文中，我们回顾了关于单胺神经递质相互作用的临床前数据，并介绍了两种在临床数据中检测单胺神经递质系统相互作用的方法。生物精神病学中得到最充分验证的发现之一是，脑脊液中的单胺代谢物相互之间存在关联。这种关联程度可能在一定程度上衡量了母体单胺神经递质系统之间的相互作用程度。另一种研究相互作用的方法是使用高香草酸/5-羟吲哚乙酸（HVA/5HIAA）和高香草酸/3-甲氧基-4-羟基苯乙二醇（HVA/MHPG）比率作为5-羟色胺-多巴胺（5HT-DA）和去甲肾上腺素-多巴胺（NE-DA）之间相互作用的指标。当将这些方法应用于精神分裂症患者时，发现与正常对照组相比，患者的单胺代谢物相关性降低。抗精神病药物治疗后，代谢物相关性显著增加，HVA/5HIAA和HVA/MPHG比率也增加，这表明抗精神病药物可能部分通过加强单胺之间的相互作用起作用。简明精神病评定量表（BPRS）评分与HVA/5HIAA和HVA/MHPG呈负相关，因此比率较高的患者症状较少，尤其是在治疗后。这些结果为单胺神经递质之间的相互作用在精神分裂症中很重要这一假说提供了直接的实验支持。本文还讨论了非典型抗精神病药物氯氮平对代谢物相关性和比率的一些影响。
