ArticleJournal of psychiatric research2016
Circulating biosignatures of late-life depression (LLD): Towards a comprehensive, data-driven approach to understanding LLD pathophysiology.
Article in Journal of psychiatric research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Evidence for Structural and Functional Alterations of Frontal-Executive and Corticolimbic Circuits in Late-Life Depression and Relationship to Mild Cognitive Impairment and Dementia: A Systematic Review.Frontiers in neuroscience · 2020Pooled it
- Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome.JAMA network open · 2022Trial
- Persistent fatigue in long-COVID is not associated with peripheral inflammatory or cellular stress biomarkers: A cross-sectional controlled study.Brain, behavior, & immunity - health · 2026Article
- Machine learning in mental health promotion for older adults: a scoping review.BMC geriatrics · 2026Article
- Premature aging in serious mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Nutritional interventions for late-life depression: evidence, mechanisms, and clinical assessment tools.Frontiers in nutrition · 2026Review
- Lipid metabolism dysregulation in late-life depression: peripheral metabolic disturbance, central lipid alterations, and dietary modulation.Frontiers in nutrition · 2026Review
- Immunopsychiatry of late life depression: role of ageing-related immune/inflammatory processes in the development and progression of depression.Acta neuropsychiatrica · 2025Review
- Elevated senescence-associated secretory phenotype index in late-life bipolar disorder.Journal of affective disorders · 2024Article
- Sex differences in plasma proteomic markers in late-life depression.Psychiatry research · 2024Article
- Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.Frontiers in aging neuroscience · 2024Article
- Protocol for a pilot clinical trial of the senolytic drug combination Dasatinib Plus Quercetin to mitigate age-related health and cognitive decline in mental disorders.F1000Research · 2024Article
- Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.Frontiers in aging · 2024Article
- Challenges in Identifying Individualized Brain Biomarkers of Late Life Depression.Advances in geriatric medicine and research · 2023Article
- Major depression and the biological hallmarks of aging.Ageing research reviews · 2023Review
- Depressive symptom profiles predict dementia onset and brain pathology in older persons. The AGES-Reykjavik study.Neurobiology of aging · 2022Article
- Increased Levels of Circulating Cell-Free mtDNA in the Plasma of Subjects With Late-Life Depression and Frailty: A Preliminary Study.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2022Article
- Depression Augments Plasma APOA4 without Changes of Plasma Lipids and Glucose in Female Adolescents Carrying G Allele of APOA4 rs5104.Journal of molecular neuroscience : MN · 2021Article
- Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Influence of genetic polymorphisms in homocysteine and lipid metabolism systems on antidepressant drug response.BMC psychiatry · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
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