Apolipoprotein A-I as a candidate serum marker for the response to lithium treatment in bipolar disorder

The molecular basis of bipolar disorder (BD) is still unknown as is the mechanism through which lithium, the therapy of choice, exerts its effects in treatment of BD. So far, no biomarkers exist to facilitate diagnosis of BD or treatment evaluation. To investigate whether BD and its treatment with lithium leaves a characteristic signature in the serum proteome, we used SELDI-TOF MS to analyze individual serum samples from BD patients treated with lithium (BD-plus-Li, n=15) or other drugs (BD-minus-Li, n=10) and from healthy controls (n=15). Interestingly, features of 28 kDa (one peak) and 14 kDa (three peaks) showed a decreased level in the BD-minus-Li group and a level restored to that of the control group in the BD-plus-Li group. To reveal the identity of these features, we subjected pooled serum samples from both BD groups to the 2-D DIGE technology and identified 28 kDa apolipoprotein A-I (apo A-I) and three 14 kDa fragments thereof as upregulated in the BD-plus-Li group. Immunoturbidimetry, a routine clinical assay, verified the characteristic apo A-I signature in individual serum samples. In conclusion, we propose apo A-I as a candidate marker that can visualize response to lithium treatment at the serum protein level.