Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology. J Psychiatr Res 2016 Nov;82:1-7
Date
07/23/2016Pubmed ID
27447786Pubmed Central ID
PMC9344393DOI
10.1016/j.jpsychires.2016.07.006Scopus ID
2-s2.0-84978670364 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
There is scarce information about the pathophysiological processes underlying Late-Life Depression (LLD). We aimed to determine the neurobiological abnormalities related to LLD through a multi-modal biomarker approach combining a large, unbiased peripheral proteomic panel and structural brain imaging. We examined data from 44 LLD and 31 control participants. Plasma proteomic analysis was performed using a multiplex immunoassay. We evaluated the differential protein expression between groups with random intercept models. We carried out enrichment pathway analyses (EPA) to uncover biological pathways and processes related to LLD. Machine learning analysis was applied to the combined dataset to determine the accuracy with which specific proteins could correctly discriminate LLD versus control participants. Sixty-one proteins were differentially expressed in LLD (p < 0.05 and FDR < 0.01). EPA showed that these proteins were related to abnormal immune-inflammatory control, cell survival and proliferation, proteostasis control, lipid metabolism, intracellular signaling. Machine learning analysis showed that a panel of three proteins (C-peptide, FABP-liver, ApoA-IV) discriminated LLD and control participants with 100% accuracy. The plasma proteomic profile in LLD revealed dysregulation in biological processes essential to the maintenance of homeostasis at cellular and systemic levels. These abnormalities increase brain and systemic allostatic load leading to the downstream negative outcomes of LLD, including increased risk of medical comorbidities and dementia. The peripheral biosignature of LLD has predictive power and may suggest novel putative therapeutic targets for prevention, treatment, and neuroprotection in LLD.
Author List
Diniz BS, Lin CW, Sibille E, Tseng G, Lotrich F, Aizenstein HJ, Reynolds CF, Butters MAAuthor
Chien-Wei Lin PhD Associate Professor in the Data Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Apolipoproteins A
Biomarkers
Blood Proteins
C-Peptide
Depression
Fatty Acid-Binding Proteins
Female
Humans
Male
Proteomics
Psychiatric Status Rating Scales
