Although many investigators have been searching for genetic markers to predict lithium response in bipolar disorders, no genetic predictor has been established yet. We previously reported the association of mitochondrial DNA (mtDNA) 5178 and 10398 polymorphisms with bipolar disorder. The objective of this study is to clarify whether these mtDNA polymorphisms can predict response to maintenance lithium treatment in bipolar patients. We examined these polymorphisms and some clinical variables in 54 bipolar patients. A logistic regression analysis was performed and revealed that patients carrying the 10398A polymorphism showed a significantly better response to lithium (p=0.03). Some clinical variables such as sex, age at onset, and rapid cycling also showed a significant association with lithium response in univariate analysis (chi2 test, p&0.05). Our findings suggest that the mtDNA 10398 polymorphism might be related to maintenance lithium treatment response.

In order to prescribe lithium appropriately to patients with bipolar disorder, predictors of lithium response are helpful. The present paper reviews the biological predictors of lithium response. As a positive predictor of lithium response, the following have been reported: strong loudness dependence of the auditory-evoked N1/P2-response; higher brain lithium concentration; lower inositol monophosphatase (IMPase) mRNA expression; higher serotonin-induced calcium mobilization; increased N -acetyl-aspartate peak and decreased myo-inositol peak; white matter hyperintensity; decreased intracellular pH; higher frequency of phospholipase C g -1 ( PLCG1 )-5 repeat and PLCG1 -8 repeat; and C973A polymorphism in the inositol polyphosphate 1-phosphatase gene. In contrast the following have been reported as a predictor of negative lithium response: epileptiform abnormality of electroencephalography; human leukocyte antigen type A3; decreased phosphocreatine peak area after photic stimulation; and homozygotes for the short variant of the serotonin transporter gene. Most of the possible biological predictors of better lithium response, such as lower IMPase mRNA levels, white matter hyperintensity, lower brain intracellular pH, enhanced calcium response, and PLCG1 -5 repeat had been detected as risk factors for bipolar disorder, suggesting that bipolar disorder responding well to maintenance lithium treatment is a distinct category having a certain neurobiological basis, although these findings need further replication. The search for biological predictors of lithium response is still in its infancy. Most of the laboratory or neuroimaging techniques used in these studies are not easily performed in clinical settings, so the development of an easy and useful laboratory test is needed.

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