Oades Robert D, Röpcke Bernd, Henning Uwe, Klimke Ansgard
Biopsychology Research Group, University Clinic for Child and Adolescent Psychiatry, Virchowstr. 174, 45147 Essen, Germany.
Behav Brain Funct. 2005 Aug 9;1:14. doi: 10.1186/1744-9081-1-14.
Some clinical symptoms or cognitive functions have been related to the overall state of monoamine activity in patients with schizophrenia, (e.g. inverse correlation of the dopamine metabolite HVA with delusions or visual-masking performance). However, profiles (as presented here) of the relations of the activity of dopamine, noradrenaline and serotonin to neuropsychologic (dys)functions in major patient sub-groups with their very different symptomatic and cognitive characteristics have not been reported.
Serum measures of dopamine, noradrenaline and serotonin turnover were examined by regression analyses for the prediction of performance on 10 neuropsychological measures reflecting left- and right-hemispheric and frontal-, parietal- and temporal-lobe function in 108 patients with schizophrenia and 63 matched controls. The neuropsychological battery included tests of verbal fluency, Stroop interference, trail-making, block-design, Mooney faces recognition, picture-completion, immediate and delayed visual and verbal recall. Paranoid and nonparanoid subgroups were based on ratings from the Positive and Negative Syndrome Scale (PANSS). Groups with high and low ratings of ideas-of-reference and thought-disorder were formed from a median split on the Scale for Assessment of Positive Symptoms (SAPS).
Verbal-fluency and Stroop-interference (left frontal and fronto-cingulate function) were negatively associated with noradrenergic turnover in nonparanoid and thought-disordered patients. High dopamine turnover related to speeded trail-making (frontal modulation of set switching) in those with many ideas-of-reference. In contrast, low dopamine turnover predicted poor recall in nonparanoid patients and those with little thought disorder. Serotonin metabolism did not independently contribute to the prediction any measure of cognitive performance. But, with regard to the relative activity between monoaminergic systems, increased HVA/5-HIAA ratios predicted visual-reproduction and Mooney's face-recognition performance (right-hemisphere functions) in highly symptomatic patients. Decreased HVA/MHPG predicted non-verbal recall.
Clinical state and function are differentially sensitive to overall levels of monoamine activity. In particular, right-lateralised cerebral function was sensitive to the relative activities of the monoamines. Increased noradrenergic activity was associated with enhanced frontal but impaired temporal lobe function in nonparanoid syndromes. Low dopaminergic activity predicted poor attentional set control in those with ideas-of-reference, but poor recall in nonparanoid patients. These data, especially the HVA/5-HIAA ratios, provide a basis for planning the nature of antipsychotic treatment aimed at patient specific symptom dimensions and cognitive abilities.
精神分裂症患者的一些临床症状或认知功能与单胺活性的整体状态有关（例如多巴胺代谢物高香草酸（HVA）与妄想或视觉掩蔽表现呈负相关）。然而，多巴胺、去甲肾上腺素和5-羟色胺活性与具有非常不同症状和认知特征的主要患者亚组的神经心理（功能）障碍之间的关系概况（如下文所述）尚未见报道。
通过回归分析检查血清中多巴胺、去甲肾上腺素和5-羟色胺周转率的测量值，以预测108例精神分裂症患者和63例匹配对照在10项反映左、右半球以及额叶、顶叶和颞叶功能的神经心理学测量中的表现。神经心理测试组包括言语流畅性测试、斯特鲁普干扰测试、连线测试、积木设计测试、穆尼面部识别测试、图片完成测试、即时和延迟视觉及言语回忆测试。偏执和非偏执亚组基于阳性和阴性症状量表（PANSS）评分划分。参照观念和思维障碍评分高和低的组由阳性症状评定量表（SAPS）的中位数划分形成。
在非偏执和思维障碍患者中，言语流畅性和斯特鲁普干扰（左额叶和额扣带回功能）与去甲肾上腺素能周转率呈负相关。高多巴胺周转率与参照观念较多者的快速连线测试（定势转换的额叶调节）有关。相反，低多巴胺周转率预示非偏执患者及思维障碍较少者的回忆能力较差。5-羟色胺代谢对任何认知表现测量的预测均无独立贡献。但是，关于单胺能系统之间的相对活性，高症状患者中HVA/5-羟吲哚乙酸（5-HIAA）比值升高预示视觉再现和穆尼面部识别表现（右半球功能）。HVA/3-甲氧基-4-羟基苯乙二醇（MHPG）比值降低预示非言语回忆能力。
临床状态和功能对单胺活性的整体水平有不同程度的敏感性。特别是，右侧大脑功能对单胺的相对活性敏感。去甲肾上腺素能活性增加与非偏执综合征中额叶功能增强但颞叶功能受损有关。低多巴胺能活性预示参照观念者的注意力定势控制能力较差，但非偏执患者的回忆能力较差。这些数据，尤其是HVA/5-HIAA比值，为针对患者特定症状维度和认知能力规划抗精神病治疗的性质提供了依据。
