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J Psychiatr Res. 2016 Nov;82:1-7. doi: 10.1016/j.jpsychires.2016.07.006. Epub 2016 Jul 11.

Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology.

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Department of Psychiatry & Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
Campbell Family Mental Health Research Institute of CAMH, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:


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.


Elderly; Late-life depression; Neurobiology; Proteomic

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