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

Abstract

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 no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Quantitative proteomic study of the plasma reveals acute phase response and LXR/RXR and FXR/RXR activation in the chronic unpredictable mild stress mouse model of depression

“…To gain insight into the pathogenesis of depression, our team previously used a proteomics approach on human plasma. However, the differential proteins in Xu et al ( 5 ) were different from those in Yang et al ( 6 ) and Song et al ( 7 ). A possible reason for the lack of concordance is variability in the factors that cause depression.…”

“…Frozen plasma samples from the two groups (CON ( n =20) and CUMS ( n =20) were thawed, and equal-volume samples from six or seven mice ( 6 , 7 ) for each group were pooled to minimize the effect of individual variation (each group therefore generated three pooled samples). The pooled plasma samples were immunodepleted of high abundance plasma proteins using a Multiple Affinity Removal LC Column-Mouse 3 (Agilent Technologies, Inc., Santa Clara, CA, USA).…”

Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study

“…Recently, researchers have investigated the psychopathological characteristics of bipolar and unipolar depression 44 and found different pathophysiologic processes underlying the depressive episodes in MDD and BD, especially in the neural circuitry regulating emotion, reward and attention 45 . Our group previously identified candidate biomarkers for diagnosing MDD 11 , 12 , 46 – 49 and BD 50 – 53 , respectively. These biomarkers are capable of accurately distinguishing MDD and BD patients from healthy controls.…”

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

“…A MetaCore analysis of BD patients at different manifestation stages showed involvement of the KKS in BD (Song et al, 2015). One study has identified polymorphisms in the B2BKR gene, which are linked to BD (Gratacòs et al, 2009).…”