Inflammatory markers and incident depression: evidence in a population-based prospective study
Abstract
The association between pro-inflammatory cytokines and depression is widely acknowledged. However, longitudinal data that show they lead to depression are few. In a community-based sample of older individuals (n = 2761, ages = 55-98 y) in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the associations between inflammatory markers (CRP, IL6, TNFα, and inflammation risk score) and depression (defined as the presence of depressive symptoms, depression history or treatment). Cross-sectional analysis showed that CRP, IL-6 and TNFα were significantly associated with depression at baseline. Longitudinal analysis controlling for a host of potentially confounding risk factors and initial depression revealed that IL-6, TNFα, and inflammation risk score were associated with elevated risk of depression at follow-ups. However, there was no significant association between CRP and subsequent depression after adjusting for sociodemographic, lifestyles and inflammatory medical condition variables. In summary, this prospective study shows that inflammation predicts depression in older adults, and suggests that the heterogeneous findings among studies may be due to differences in study population characteristics, depression, inflammatory markers, and the extent of adjusting for confounders.
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Patients with elevated inflammatory markers often show better outcomes with anti-inflammatory treatments and poorer responses to psychotherapy.
“Patients with elevated inflammatory markers often show better outcomes with anti-inflammatory treatments and poorer responses to psychotherapy, supporting stratified therapeutic approaches (Shi et al., 2022; Jha et al., 2017; Orsolini et al., 2022; Pan et al., 2022).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Shi et al., 2022
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- Authors
- Shi, R., Gwee, X., Chua, D. Q., Tan, C. T., Yap, K. B., Larbi, A., Lu, Y., & Ng, T. P.
- Affiliations
- Shandong University (CN)
- National University of Singapore (SG)
- Agency for Science, Technology and Research (SG)
- Ng Teng Fong General Hospital (SG)
- Corresponding author
- Lu, Yanxia
- Ng, Tze Pin
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 142
- Pages
- 105806
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W4281392218
- Cited by
- 23
- References
- 54
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 5 · 2023: 1 · 2022: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Health › Health disparities and outcomes
- Keywords
- depression, inflammatory markers, inflammatory cytokines, C-reactive protein, interleukin-6, TNF-α, older adults, incident depression
- MeSH terms
- Aged, Aged, 80 and over, C-Reactive Protein, Cross-Sectional Studies, Depression, Humans, Inflammation, Longitudinal Studies, Middle Aged, Prospective Studies, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6
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