Search for peripheral biomarkers in patients with psychotic bipolar disorder vs controls: a proteomic approach.

Background. Data on neurobiological mechanisms underlying mood disorders are elusive, aetiology of such states is multifactorial including genetic predisposition and environmental factors. Diagnosis is currently made solely on interview-based methodology. Biological markers which could improve the current classification and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. We describe here the preliminary data on a proteomic analysis from peripheral lymphocytes of patients with acutely psychotic bipolar disorder, compared with a group of subjects with depression and no personal or family history of psychosis and a group of demographically matched healthy controls. Methods. Patients were sampled and evaluated by means of SCID-I, PANSS, YMRS, HAM-A, HAM-D. Lymphocytes have been separated and Two-dimensional electrophoresis (2-DE) was carried out on protein extracts. Analysis was performed using Progenesis Same Spot software. Results. 12 acutely psychotic patients with bipolar disorder have been recruited as well as 8 patients with mild to moderate depression. Acutely psychotic patients were on a PRN (as required) medication regimen since 1-2 days before blood taking. Patients with depression were on a regular therapy with SSRIs (2 patients also mood stabilizers). 12 healthy volunteers matched for age, gender and exclusion criteria were also recruited. 2-DE shows significant differences in protein pattern between the three groups. PCA underlies a clear separation between controls and patients groups, with a t1 value for the first component of 63,96%. T- Test for independent samples shows that 48 protein spots were found to be differentially expressed in patients compared to controls (p<0.001), with an increase in expression for most spots in patients and a decrease in expression for 6 spots. Comparison between patients groups shows 6 protein spots differentially expressed with statistical significance (p <0.001). Conclusions. Preliminary analyses on a small sample show significant differences in protein pattern for both patients groups compared with healthy control. Patients with acutely psychotic bipolar disorder and patients with depression may have some distinct peripheral biomarkers as well as common patterns of protein expression. Proteins are currently under identification using Mass Spectrometry and this could shed light into neurobiological mechanisms involved in the pathogenesis of the disorders.