Oades Robert D, Klimke Ansgard, Henning Uwe, Rao Marie Luise
University of Essen Clinic for Child and Adolescent Psychiatry and Psychotherapy, Essen, Germany.
Hum Psychopharmacol. 2002 Jan;17(1):15-27. doi: 10.1002/hup.368.
Plasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (e.g. HVA/deficit syndrome) and sometimes the symptoms (e.g. HVA/anhedonia). But, such studies have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. We hypothesized that comparing the major symptom dimensions to measures of transmitter activity (with and without control for antipsychotic drug treatment) would show differential patterns of activity useful for the design of pharmacological treatments.
Dopamine (DA), noradrenaline (NA), serotonin (5-HT), their three major metabolites and prolactin were measured in the serum of 108 patients with schizophrenia and 63 matched controls: DA D2-receptor blocking-activity was estimated from a regression of butyrophenone displacement in striatum in vitro on to PET reports of drug-binding in vivo. Symptoms were factored into four dimensions (disorganized/thought disorder, nonparanoid/negative, ideas-of-reference and paranoid/positive symptoms).
(1). Patients' DA activity did not differ from controls: but their 5-HT and NA turnovers increased/decreased, respectively, and the DA/5HT-metabolite ratio was lower. Increased DA-D2-receptor occupancy was predicted by decreased DA-metabolism and its ratio to 5-HT-metabolism. (2). Patients had higher levels of NA, DA-metabolites and DA-/5-HT-metabolite ratios on atypical vs typical drugs. (3). Increased D2-occupancy was associated with lower DA metabolism in paranoid patients but was unrelated to relative increases of DA/5-HT- and NA-metabolism in nonparanoid patients. (4). Low DA-/5-HT-metabolite ratios, high prolactin and low DA-metabolism characterized thought-disordered patients. (5). High DA-/5-HT-metabolite ratios paralleled many ideas-of-reference. The metabolites were sensitive, respectively, to control for D2-occupancy and prolactin.
The role of DA in paranoid, and 5-HT in thought-disordered and ideas-of-reference dimensions point both to the mechanisms underlying the features typical of these subgroups and the type of medication appropriate.
单胺能活性的血浆和血清指标部分反映了精神分裂症的病情（如高香草酸/缺陷综合征），有时也反映症状（如高香草酸/快感缺乏）。但是，此类研究很少同时考虑代谢物和母体胺类或胺类间活性比率。我们推测，将主要症状维度与递质活性指标进行比较（无论是否考虑抗精神病药物治疗的影响），会显示出对药物治疗设计有用的不同活性模式。
对108例精神分裂症患者和63例匹配的对照者的血清进行多巴胺（DA）、去甲肾上腺素（NA）、5-羟色胺（5-HT）、它们的三种主要代谢物以及催乳素的检测：通过体外纹状体中丁酰苯取代的回归与体内药物结合的PET报告之间的关系来估算DA D2受体阻断活性。症状被归纳为四个维度（紊乱/思维障碍、非偏执/阴性、牵连观念和偏执/阳性症状）。
（1）患者的DA活性与对照者无差异：但其5-HT和NA周转率分别升高/降低，且DA/5-HT代谢物比率较低。DA代谢及其与5-HT代谢的比率降低预示着DA-D2受体占有率增加。（2）与典型药物相比，患者使用非典型药物时NA、DA代谢物水平以及DA/5-HT代谢物比率更高。（3）偏执型患者中D2占有率增加与DA代谢降低有关，但与非偏执型患者中DA/5-HT和NA代谢的相对增加无关。（4）思维紊乱患者的特征是DA/5-HT代谢物比率低、催乳素水平高以及DA代谢低。（5）高DA/5-HT代谢物比率与许多牵连观念平行。这些代谢物分别对D2占有率和催乳素的控制敏感。
DA在偏执维度中的作用以及5-HT在思维紊乱和牵连观念维度中的作用，既指出了这些亚组典型特征背后的机制，也指出了合适的药物类型。
