Change of Dopamine Receptor mRNA Expression in Lymphocyte from Schizophrenic Patients

Kwak, Yong Tae; Choi, Chul Hee; Kim, Ok Jun; Joo, Yeon Ho; Kim, Hyeong Seob; Kang, Seong Suk; Koo, Min Seong; Sunwoo, Il Nam

Abstract

OBJECTIVES: Schizophrenia, commonly developed in adolescence and young adulthood, is one of the most common mental diseases in psychiatry. The etiology or pathogenesis of this disease is uncertain yet, but the dysfunction of dopaminergic system in the brain has been proposed. However, there is no direct evidence of dysfunction of brain dopaminergic systems in schizophrenic patients because the direct assessment of brain dopaminergic systems is almost impossible at present. To overcome this problem, recently founded dopamine receptors and their mRNAs in peripheral lymphocytes was used. The purpose of this study was to define whether the dopamine receptors of peripheral lymphocytes can be the peripheral markers of schizophrenia or not.
METHODS
The total numbers of subjects are 87 schizophrenic patients. Among them 44 patients were schizophrenics who had been taking antipsychotic drugs for more than 3 years(medicated patients) 43 schizophrenics who recently are not taken antipsychotic drugs for more than 3 months(drugfree patients) For controls age and sex matched 31 healthy persons were enrolled. Sequential reverse transcription and quantitative polymerase chain reaction of the mRNA were used to investigate the expression of dopamine receptors in peripheral lymphocytes. The gene expression of dopamine receptors were compared in each groups and after starting antipsychotic medicines in drug-free patients, the clinical scales and the dopamine receptors of peripheral lymphocytes were sequentially studied before, 2 weeks after and 8 weeks after medication.
RESULTS
1)In drug-free schizophrenics, D3 dopamine receptor mRNA expression of peripheral lymphocytes was significantly increased comparing with that of controls and drug-medicated schizophrenics and D5 dopamine receptor mRNA expression was increased comparing with only that of drug-medicated schizophrenics. There was no difference between controls and drug-medicated schizophrenics. 2)After antipsychotic medication, dopamine receptors of lymphocytes were increased tendency. 3)Drug-free patients were divided into two groups according to dopamine receptor expression in controls to evaluate the significance of increased dopamine receptor expression. The group of patients with increased dopamine receptor expression had following clinical characteristics. (1)More severe psychiatric symptoms (2)Poor pharmacological response of pBPRS on medicines (3)Severe extrapyramidal side effects after pharmacological treatment
CONCLUSION
These results revealed that the molecular biologically determined dopamine receptors of peripheral lymphocytes were reactive, and increased expression of dopamine receptor in peripheral lymphocyte had clinical significance for subgrouping and prognostication. These findings suggested that dopamine receptors of peripheral lymphocyte may represent dopamine receptors of the brain, even the location cannot be determined.