title: 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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Y R
authors.initials: YR
authors.lastname: Song
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Yang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Shi
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: C L
authors.initials: CL
authors.lastname: Huang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Pan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: P
authors.initials: P
authors.lastname: Xie
mesh_terms: D000293:Adolescent; D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood*; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood*; D001714:Bipolar Disorder / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D024401:Carbonic Anhydrase I / Q000097:blood*; D030562:Databases, Protein; D003865:Major Depressive Disorder / Q000175:diagnosis; D003937:Diagnosis, Differential; D018450:Disease Progression; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D052439:Lipid Metabolism Disorders / Q000150:complications / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D040901:Proteomics; D055815:Young Adult
chemical_list: C108666:APOL1 protein, human; D016632:Apolipoprotein A-I; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D024401:Carbonic Anhydrase I