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

Abstract

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.

Potential Biomarkers Selection for Bipolar Disorder Identification

“…There is considerable similarity across the apo family and previous studies on apo AI have noted that, in BD patients, the Apo I level is increased which is consistent with prior findings by Herberth (Herberth et al, 2011;Sussulini et al, 2011;Pruijm, et al, 2013). Furthermore, we found that Apo A II was a significant risk factor (OR=1.2 per one standard deviation increase) for BD.…”

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders

“…Apolipoprotein A1 appeared to follow the same pattern, with decreased serum levels in drug-free bipolar disorder patients with an increase back to control levels following lithium treatment (Sussulini et al, 2011). However, other studies indicated unchanged or decreased Apo A1 serum levels in medicated bipolar disorder patients (Sussulini et al, 2011;Haenisch et al, 2013;Herberth et al, 2011b;Sussulini et al, 2010).…”

Proteomic Analysis of Lymphoblastoid Cells Derived from Monozygotic Twins Discordant for Bipolar Disorder: A Preliminary Study

“…Biomarker research in other tissues such as serum, plasma, cerebrospinal fluids, saliva, and urine have also been performed [20], [21] but has not led to a diagnostic test.…”