Cerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry

BMC Psychiatry

Avery D. Franzen¹  Samuel S. Newton²  Monica Sathyanesan²  Linda L. Carpenter³  Vikas Kumar⁴  Ronald S. Duman⁵  Tukiet T. Lam⁶  Kenneth R. Williams⁷  Angus C. Nairn⁸ 

[1] Basic Biomedical Science Department, University of South Dakota, 414 E Clark St, 57069, Vermillion, SD, USA;Basic Biomedical Science Department, University of South Dakota, 414 E Clark St, 57069, Vermillion, SD, USA;Sioux Falls V A Health Care System, 57105, Sioux Falls, SD, USA;Brown Department of Psychiatry and Human Behavior, Butler Hospital, 345 Blackstone Boulevard, 02906, Providence, RI, USA;Mass Spectrometry & Proteomics Core Facility, University of Nebraska Medical Center, 985875 Nebraska Medical Center, 68198, Omaha, NE, USA;Yale Psychiatry, 34 Park Street, 06508, New Haven, CT, USA;Yale/Keck MS & Proteomics Resource, 300 George Street, Ste G001, 06511, New Haven, CT, USA;Yale/NIDA Neuroproteomics Center, 300 George Street, 06511, New Haven, CT, USA;Molecular Biophysics and Biochemistry, Yale University School of Medicine, 067511, New Haven, CT, USA;Yale/NIDA Neuroproteomics Center, 300 George Street, 06511, New Haven, CT, USA;Molecular Biophysics and Biochemistry, Yale University School of Medicine, 067511, New Haven, CT, USA;Yale/NIDA Neuroproteomics Center, 300 George Street, 06511, New Haven, CT, USA;Yale Psychiatry, 34 Park Street, 06508, New Haven, CT, USA;

关键词: Cerebrospinal fluid;    Proteomics;    Label free quantitation;    Major depressive disorder;    Depression;    Inflammation;    Metabolism;    Interleukin 6;    Oncostatin M;    STAT3;   

DOI  :  10.1186/s12888-020-02874-9

来源: Springer

【 摘 要 】

BackgroundDepression affects approximately 7.1% of the United States population every year and has an annual economic burden of over $210 billion dollars. Several recent studies have sought to investigate the pathophysiology of depression utilizing focused cerebrospinal fluid (CSF) and serum analysis. Inflammation and metabolic dysfunction have emerged as potential etiological factors from these studies. A dysregulation in the levels of inflammatory proteins such as IL-12, TNF, IL-6 and IFN-γ have been found to be significantly correlated with depression.MethodsCSF samples were obtained from 15 patients, seven with major depressive disorder and eight age- and gender-matched non-psychiatric controls. CSF protein profiles were obtained using quantitative mass spectrometry. The data were analyzed by Progenesis QI proteomics software to identify significantly dysregulated proteins. The results were subjected to bioinformatics analysis using the Ingenuity Pathway Analysis suite to obtain unbiased mechanistic insight into biologically relevant interactions and pathways.ResultsSeveral dysregulated proteins were identified. Bioinformatics analysis indicated that the potential disorder/disease pathways include inflammatory response, metabolic disease and organismal injury. Molecular and cellular functions that were affected include cellular compromise, cell-to-cell signaling & interaction, cellular movement, protein synthesis, and cellular development. The major canonical pathway that was upregulated was acute phase response signaling. Endogenous upstream regulators that may influence dysregulation of proinflammatory molecules associated with depression are interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), oncostatin M, PR domain zinc finger protein 1 (PRDM1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A).ConclusionsThe proteome profiling data in this report identifies several potential biological functions that may be involved in the pathophysiology of major depressive disorder. Future research into how the differential expression of these proteins is involved in the etiology and severity of depression will be important.

【 授权许可】

CC BY