Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2%of the general population of different European countries. Unfortunately, there is noobjective laboratory-based test to aid BD diagnosis or monitor its progression, andlittle is known about the molecular basis of BD. Here, we performed a comparativeproteomic study to identify differentially expressed plasma proteins in various BDmood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. Atotal of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matchedhealthy control subjects were recruited. Seven high-abundance proteins wereimmunodepleted in plasma samples from the 4 experimental groups, which were thensubjected to proteome-wide expression profiling by two-dimensional electrophoresisand matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandemmass spectrometry. Proteomic results were validated by immunoblotting andbioinformatically analyzed using MetaCore. From a total of 32 proteins identifiedwith 1.5-fold changes in expression compared with healthy controls, 16 proteins wereperturbed in BD independent of mood state, while 16 proteins were specificallyassociated with particular BD mood states. Two mood-independent differentialproteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may beassociated with early perturbations in lipid metabolism. Moreover, down-regulation ofone mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involvedin the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may beassociated with early perturbations in lipid metabolism that are independent of moodstate, while CA-1 may be involved in the pathophysiology of depressive episodes.