Cerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry

Avery D. Franzen, Tukiet T. Lam, Kenneth R. Williams, Angus C. Nairn, Ronald S. Duman, Monica Sathyanesan, Vikas Kumar, Linda L. Carpenter, Samuel S. Newton

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Depression 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-γhave been found to be significantly correlated with depression. Methods: CSF 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. Results: Several 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). Conclusions: The 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.

Original languageEnglish (US)
Article number481
JournalBMC Psychiatry
Volume20
Issue number1
DOIs
StatePublished - Oct 1 2020
Externally publishedYes

Keywords

  • Cerebrospinal fluid
  • Depression
  • Inflammation
  • Interleukin 6
  • Label free quantitation
  • Major depressive disorder
  • Metabolism
  • Oncostatin M
  • Proteomics
  • STAT3

ASJC Scopus subject areas

  • Psychiatry and Mental health

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