Korean Journal of Biological Psychiatry

Objective：Lithium inhibits the action of inositol monophosphatase(IMPase) in phosphoinositide(PI) signal transduction system at therapeutically relevant concentration. The depletion of inositol by lithium itself cannot explain the lithium's therapeutic effect. However, attention has focused on the abnormality of PI signal transduction system as the pathophysiology of bipolar affective disorder(BPD). We investigated whether IMPase mRNA levels of lymphocytes would be different between BPD patients(n=16) and age, sex-matched normal controls(n=16). We also investigated the change of IMPase mRNA level by lithium during 4 weeks to probe the possibility that IMPase mRNA levels could predict the therapeutic response to lithium and clinical course.

Method：Relative IMPase mRNA levels in lymphocyte were quantified by reverse transcriptase(RT)-PCR in sixteen drug-free BPD patients and sex, age-matched normal controls. The psychopathology of patients were measured using YMRS(Young Mania Rating Scale) and CGI(Clinical Global Impression). 

Results：There was no significant difference in IMPase mRNA levels between BPD patients and normal controls. And the IMPase mRNA levels were not significantly changed by 4 week treatment with lithium. However, the basal IMPase mRNA levels were negatively correlated with the changes of CGI after 4 weeks. Furthermore, the patients with relatively high basal IMPase mRNA levels showed much more improvement during 4 weeks.

Conclusions：BPD patients and normal controls were not distinguished by lymphocyte IMPase mRNA level. Although we do not support the hypothesis that lymphocyte IMPase activity would be related with the pathogenesis of BPD and the action of lithium, these data raise the possibility that lymphocyte IMPase mRNA levels could function as a predictor of therapeutic response and clinical course of BPD.

Keywords Lithium;Inositol monophosphatase mRNA;Bipolar affective disorder;Lymphocyte.