Kwak Y T, Koo M S, Choi C H, Sunwoo I
Department of Neurology, Yong-in Hyoja Geriatric Hospital, Yong-in, Korea
BMC Med Genet. 2001;2:3. doi: 10.1186/1471-2350-2-3. Epub 2001 Mar 5.
Though the dysfunction of central dopaminergic system has been proposed, the etiology or pathogenesis of schizophrenia is still uncertain partly due to limited accessibility to dopamine receptor. The purpose of this study was to define whether or not the easily accessible dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia.
44 drug-medicated schizophrenics for more than 3 years, 28 drug-free schizophrenics for more than 3 months, 15 drug-naïve schizophrenic patients, and 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of D3 and D5 dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors was compared in each group. After taking antipsychotics in drug-free and drug-naïve patients, the dopamine receptors of peripheral lymphocytes were sequentially studied 2nd week and 8th week after medication. In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes significantly increased compared to that of controls and drug-medicated schizophrenics, and D5 dopamine receptor mRNA expression increased compared to that of drug-medicated schizophrenics. After taking antipsychotics, mRNA of dopamine receptors peaked at 2nd week, after which it decreases but the level was above baseline one at 8th week. Drug-free and drug-naïve patients were divided into two groups according to dopamine receptor expression before medications, and the group of patients with increased dopamine receptor expression had more severe psychiatric symptoms.
These results reveal that the molecular biologically-determined dopamine receptors of peripheral lymphocytes are reactive, and that increased expression of dopamine receptor in peripheral lymphocyte has possible clinical significance for subgrouping of schizophrenis.
尽管中枢多巴胺能系统功能障碍已被提出,但精神分裂症的病因或发病机制仍不确定,部分原因是多巴胺受体难以获取。本研究的目的是确定外周淋巴细胞中易于获取的多巴胺受体是否可作为精神分裂症的外周标志物。
纳入了44例服用药物超过3年的精神分裂症患者、28例停药超过3个月的精神分裂症患者、15例未服用过药物的精神分裂症患者以及31名健康人。采用mRNA的序列逆转录和定量聚合酶链反应来研究外周淋巴细胞中D3和D5多巴胺受体的表达。比较了每组中多巴胺受体的基因表达。在未服药和未服用过药物的患者服用抗精神病药物后,分别在服药后第2周和第8周对外周淋巴细胞的多巴胺受体进行了研究。在未服药的精神分裂症患者中,外周淋巴细胞的D3多巴胺受体mRNA表达与对照组和服用药物的精神分裂症患者相比显著增加,D5多巴胺受体mRNA表达与服用药物的精神分裂症患者相比增加。服用抗精神病药物后,多巴胺受体的mRNA在第2周达到峰值,之后下降,但在第8周时水平仍高于基线。根据服药前多巴胺受体表达情况将未服药和未服用过药物的患者分为两组,多巴胺受体表达增加的患者组精神症状更严重。
这些结果表明外周淋巴细胞中分子生物学测定的多巴胺受体具有反应性,外周淋巴细胞中多巴胺受体表达增加对精神分裂症的亚组划分可能具有临床意义。