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Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample
Open accessAbstract
Background: Recent work suggests that epigenetic differences may be associated with psychiatric disorders. Here we investigate, in a community-based sample, whether methylation profiles distinguish between individuals with and without lifetime depression. We also investigate the physiologic consequences that may be associated with these profiles. Method: Using whole blood-derived genomic DNA from a subset of participants in the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assess genome-wide methylation profiles for over 14 000 genes in 33 persons who reported a lifetime history of depression and 67 non-depressed adults. Bioinformatic functional analyses were performed on the genes uniquely methylated and unmethylated in each group, and inflammatory biomarkers [interleukin (IL)-6 and C-reactive protein (CRP)] were measured to investigate the possible functional significance of the methylation profiles observed. Results: Uniquely unmethylated gene sets distinguished between those with versus without lifetime depression. In particular, some processes (e.g. brain development, tryptophan metabolism) showed patterns suggestive of increased methylation among individuals with depression whereas others (e.g. lipoprotein) showed patterns suggestive of decreased methylation among individuals with depression. IL-6 and CRP levels were elevated among those with lifetime depression and, among those with depression only, IL-6 methylation showed an inverse correlation with circulating IL-6 and CRP. Conclusions: Genome-wide methylation profiles distinguish individuals with versus without lifetime depression in a community-based setting, and show coordinated signals with pathophysiological mechanisms previously implicated in the etiology of this disorder. Examining epigenetic mechanisms in concert with other dynamic markers of physiologic functioning should improve our understanding of the neurobiology of depression.
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“Additionally, inflammatory markers have been associated with epigenetics at the gene level in peripheral leukocytes (Sun, Lazarus, et al., 2013; Uddin et al., 2011), which play a critical role in acute and chronic inflammation related to pathophysiology of many human diseases.”
From Integrative Analysis of Multi-omics Data for Discovery and Functional Studies of Complex Human Diseases (2016) · cites this paper as Uddin et al., 2011
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The Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136
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Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.013 · Cited by 513
Sun, Y. V., & Hu, Y.-J. (2016) · Advances in Genetics · doi:10.1016/bs.adgen.2015.11.004 · Cited by 459
Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., Ressler, K. J., & Binder, E. B. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32278 · Cited by 355
Metadata
- Authors
- Uddin, M., Koenen, K. C., Aiello, A. E., Wildman, D. E., de los Santos, R., & Galea, S.
- Affiliations
- University of Michigan (US)
- Harvard University (US)
- Wayne State University (US)
- Columbia University (US)
- Corresponding author
- Uddin, M.
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2010-09-14
- Volume
- 41
- Issue
- 5
- Pages
- 997-1007
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC3065166
- OpenAlex
- W2130775735
- Cited by
- 174
- References
- 60
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 15 · 2014: 28 · 2013: 16 · 2012: 15
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Psychological Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wayne State University (RC1MH088283, DA022720, MH07627)
- University of Michigan (RC1MH088283, MH07627, DA022720)
- National Institutes of Health (MH07627, AG013283)
- National Institute on Aging (P30AG013283, AG‐013283)
- National Institute of Mental Health (R01MH078928, RC1MH088283, MH-078928, MH07627)
- National Institute on Drug Abuse (DA 022720, R01DA022720, DA 022720-S1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, DNA methylation, epigenetics, interleukin-6, C-reactive protein, inflammatory markers, tryptophan metabolism, brain development, lipoprotein metabolism, neurobiology of depression
- MeSH terms
- Adult, C-Reactive Protein, Depressive Disorder, Female, Humans, Inflammation, Male, Michigan, Biomarkers, Interleukin-6, Cluster Analysis, Case-Control Studies, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study
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