Vogel Matthias, Pfeifer Silvia, Schaub Rainer T, Grabe Hans-Jörgen, Barnow Sven, Freyberger Harald J, Cascorbi Ingolf
Department of Psychiatry and Psychotherapy, Ernst Moritz Arndt University, Greifswald, Germany.
Neuropsychobiology. 2004;50(4):305-10. doi: 10.1159/000080958.
Previous studies found an elevation of the dopamine D3 receptor (DRD3) mRNA as determined in peripheral lymphocytes in schizophrenic patients. The aim of this study was to test the hypothesis of elevated DRD3 mRNA in schizophrenia compared to bipolar disorder. Twenty-four patients, 13 schizophrenic and 11 bipolar, were included according to DSM-IV criteria. Psychometric measures were conducted using the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Montgomery-Asberg Depression Rating Scale and Young Mania Rating Scale. mRNA was isolated from lymphocytes of venous blood samples and DRD3 mRNA was quantified using real-time reverse transcription PCR. We found a decrease in DRD3 mRNA in 13 schizophrenic (p = 0.009) and 11 bipolar (p = 0.023) patients as compared to controls. Medication history and severity of positive symptoms did not significantly influence DRD3 expression. Higher levels of DRD3 mRNA were correlated with negative schizophrenic symptoms. Interestingly, after treatment of patients with antipsychotics, DRD3 mRNA levels increased to similar levels as those of healthy controls. Bipolar patients, however, showed a slower increase in DRD3 mRNA levels after 3 weeks of therapy. Our findings suggest that the expression of DRD3 mRNA is reduced in schizophrenia and bipolar disorder, supporting the hypothesis of distorted homeostasis of dopamine receptor subtypes in psychotic disorder. The observed diminution was not specific for schizophrenia but also for bipolar disorder requiring further analysis of the regulatory factors involved in dopamine receptor subtype expression.
先前的研究发现,精神分裂症患者外周淋巴细胞中的多巴胺D3受体(DRD3)mRNA水平有所升高。本研究的目的是验证与双相情感障碍相比,精神分裂症患者DRD3 mRNA水平升高这一假设。根据《精神疾病诊断与统计手册》第四版(DSM-IV)标准,纳入了24名患者,其中13名精神分裂症患者和11名双相情感障碍患者。使用阳性症状评定量表、阴性症状评定量表、简明精神病评定量表、蒙哥马利-阿斯伯格抑郁评定量表和杨氏躁狂评定量表进行心理测量。从静脉血样本的淋巴细胞中分离mRNA,并使用实时逆转录聚合酶链反应对DRD3 mRNA进行定量。我们发现,与对照组相比,13名精神分裂症患者(p = 0.009)和11名双相情感障碍患者(p = 0.023)的DRD3 mRNA水平降低。用药史和阳性症状的严重程度对DRD3表达没有显著影响。较高水平的DRD3 mRNA与精神分裂症的阴性症状相关。有趣的是,在使用抗精神病药物治疗患者后,DRD3 mRNA水平升高至与健康对照组相似的水平。然而,双相情感障碍患者在治疗3周后DRD3 mRNA水平升高较慢。我们的研究结果表明,精神分裂症和双相情感障碍患者中DRD3 mRNA的表达降低,支持了精神障碍中多巴胺受体亚型稳态失衡的假设。观察到的减少并非精神分裂症所特有,双相情感障碍也存在,这需要进一步分析参与多巴胺受体亚型表达的调节因素。