Cited by 174Epigenetics and DNA MethylationTryptophan and brain disordersStress Responses and Cortisol

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Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample

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Uddin, M., Koenen, K. C., Aiello, A. E., Wildman, D. E., de los Santos, R., Galea, S.·2011·Psychological Medicine

DOI 10.1017/s0033291710001674PMC PMC3065166

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Abstract

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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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.
ORCID: Uddin, M.
Koenen, K. C.
Aiello, A. E.
Wildman, D. E.
Galea, S.
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
DOI: 10.1017/s0033291710001674
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
Licence: www.cambridge.org/core/terms (unspecified)
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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Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample

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