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Title

Proteomic Evaluation of Cerebrospinal Fluid in Major Depressive Disorder Patients

Document Type

Oral/Panel

Publication Date

5-2020

Abstract

Depression affects approximately 7.1% of the United States population every year and has an economic burden of over $210 billion dollars annually. Several recent studies have attempted to investigate the pathophysiology of depression utilizing cerebrospinal fluid (CSF) and serum analysis. Inflammation and metabolic dysfunction have been strongly implicated as potential etiological factors. Inflammatory proteins such as IL-12, TNF, IL-6, IFN-γ, IL-9, IL-17A, and IL-10 have been found to be significantly correlated with depression. Methods: CSF samples were obtained from patients diagnosed with major depressive disorder and matched for age and gender with 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 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 and abnormalities. Molecular and cellular functions that were affected are cellular compromise, cell-to-cell signaling & interaction, cellular movement, protein synthesis, and cellular development. The major canonical pathway that was regulated was acute phase response signaling. Endogenous upstream regulators that may influence 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 disrupted in major depressive disorder's pathophysiology. Future research into how the differential expression of these proteins is involved in the etiology and severity of depression will be important.

First Advisor

Samuel Sathyanesan

Research Area

Basic Biomedical Science

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