Cerebrospinal fluid proteome evaluation in major depressive disorder by mass spectrometry

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-γ have 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.

Cerebrospinal fluid irisin and lipoxin A4 are reduced in elderly Brazilian individuals with depression: Insight into shared mechanisms between depression and dementia

“…Our results further align with recent proteomic pro-filing data indicating reduced activation of peroxisome proliferatoractivated receptor γ co-activator-1α (PGC-1α), an upstream regulator of FNDC5/irisin expression, in the CSF of patients with depression. 43 It remains to be determined whether changes in brain and plasma irisin occur throughout the lifespan, and whether they are related to a reduction in irisin expression, increased turnover in the brain, or impaired transport across the blood-brain barrier (BBB).…”

Peripheral signature of altered synaptic integrity in young onset Cannabis Use Disorder: A proteomic study of circulating extracellular vesicles

“…Mascot search parameters are found in Franzen et al (2020) 23 , and with protein requirements of at least 1 unique peptide with peptide score >30 (e.g. 95% confidence).…”

Annual Research Review: Neuroimmune network model of depression: a developmental perspective

“…In the central nervous system, individuals with depression exhibit increased inflammatory biomarkers in the cerebrospinal fluid, which flows in and around the hollow spaces of the brain and spinal Neuroimmune network model of depression cord (Felger et al, 2020;Franzen et al, 2020).…”

“…In the central nervous system, individuals with depression exhibit increased inflammatory biomarkers in the cerebrospinal fluid, which flows in and around the hollow spaces of the brain and spinal cord (Felger et al., 2020; Franzen et al., 2020). Postmortem studies of individuals with depression who died by suicide demonstrate increased inflammatory cytokines in brain tissue compared to nonpsychiatric controls, as well as increased activation of the microglia, which are the immune cells of the brain (Enache, Pariante, & Mondelli, 2019; Pandey, 2017; Torres‐Platas, Cruceanu, Chen, Turecki, & Mechawar, 2014).…”