Hsiao J K, Colison J, Bartko J J, Doran A R, Konicki P E, Potter W Z, Pickar D
Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Md.
Arch Gen Psychiatry. 1993 Aug;50(8):606-14. doi: 10.1001/archpsyc.1993.01820200016002.
To study recent suggestions by a number of investigators that interactions between monoamine neurotransmitter systems play an important role in schizophrenia. It has not been clear how hypotheses about interactions might be tested in clinical data. One means for indexing interactions between monoamine neurotransmitter systems may be to compare correlations between cerebrospinal fluid (CSF) monoamine metabolite (homovanillic acid [HVA], 5-hydroxyindoleacetic acid [5-HIAA], and 3-methoxy-4-hydroxyphenylglycol [MHPG]) or ratios of these metabolites (HVA/5-HIAA and HVA/MHPG).
We compared these putative measures of monoamine neurotransmitter interaction in 50 drug-free patients with schizophrenia (hospitalized on an inpatient ward of a tertiary care hospital) and 33 normal controls and examined the effects of neuroleptic antipsychotic treatment on these measures in 41 patients (22 of whom had antecedent drug-free CSF data).
Drug-free patients with schizophrenia had significantly smaller correlations between CSF monoamine metabolites than normal controls. Longer drug-free time was associated with even smaller correlations between metabolites, suggesting that the difference between controls and patients was not due to acute drug withdrawal. After treatment with neuroleptic antipsychotics there were significant increases in the HVA/5-HIAA and HVA/MHPG ratios, as well as increases in correlations between monoamine metabolites. After treatment, there were no significant differences in metabolite correlations between patients and controls. Metabolite ratios and correlations did not predict subsequent treatment response, but preliminary analyses demonstrated negative relationships between HVA/5-HIAA and HVA/MHPG ratios and Brief Psychiatric Rating Scale rating at that time.
The present findings are consistent with and support hypotheses suggesting that interactions between monoamine systems are altered in schizophrenia and that antipsychotic treatment may affect the functional balance between different monoamine neurotransmitters (although one should keep in mind factors other than interactions between monoamine systems that affect metabolite correlations and ratios.
研究一些研究者最近提出的单胺神经递质系统之间的相互作用在精神分裂症中起重要作用的观点。目前尚不清楚如何在临床数据中检验关于相互作用的假说。一种用于衡量单胺神经递质系统之间相互作用的方法可能是比较脑脊液（CSF）中单胺代谢物（高香草酸 [HVA]、5-羟吲哚乙酸 [5-HIAA] 和 3-甲氧基-4-羟基苯乙二醇 [MHPG]）之间的相关性，或这些代谢物的比率（HVA/5-HIAA 和 HVA/MHPG）。
我们比较了 50 例未服用药物的精神分裂症患者（在一家三级护理医院的住院病房住院）和 33 名正常对照者中这些假定的单胺神经递质相互作用指标，并在 41 例患者（其中 22 例有之前未服用药物时的脑脊液数据）中研究了抗精神病药物治疗对这些指标的影响。
未服用药物的精神分裂症患者脑脊液中单胺代谢物之间的相关性明显低于正常对照者。未服用药物的时间越长，代谢物之间的相关性越小，这表明对照者与患者之间的差异并非由于急性停药所致。使用抗精神病药物治疗后，HVA/5-HIAA 和 HVA/MHPG 比率显著升高，单胺代谢物之间的相关性也增加。治疗后，患者与对照者之间代谢物相关性无显著差异。代谢物比率和相关性不能预测随后的治疗反应，但初步分析表明，当时 HVA/5-HIAA 和 HVA/MHPG 比率与简明精神病评定量表评分之间呈负相关。
目前的研究结果与以下假说一致并支持这些假说，即精神分裂症中单胺系统之间的相互作用发生改变，抗精神病药物治疗可能会影响不同单胺神经递质之间的功能平衡（尽管应牢记影响代谢物相关性和比率的因素除了单胺系统之间的相互作用之外还有其他因素）。
