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

Published online by Cambridge University Press:  14 September 2010

M. Uddin ,
K. C. Koenen ,
A. E. Aiello ,
D. E. Wildman ,
R. de los Santos  and
S. Galea
M. Uddin*
Affiliation:
Center for Social Epidemiology and Population Health and Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
K. C. Koenen
Affiliation:
Departments of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, MA, USA
A. E. Aiello
Affiliation:
Center for Social Epidemiology and Population Health and Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
D. E. Wildman
Affiliation:
Center for Molecular Medicine and Genetics and Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
R. de los Santos
Affiliation:
Center for Social Epidemiology and Population Health and Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
S. Galea
Affiliation:
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
*
*Address for correspondence: M. Uddin, Ph.D., Assistant Research Scientist, University of Michigan School of Public Health, Department of Epidemiology, 1415 Washington Heights, Ann Arbor, MI 48109-2029, USA. (Email: [email protected])
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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.

Keywords

Epidemiologyinflammationmethylationpsychiatry
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 5 , May 2011 , pp. 997 - 1007
Copyright
Copyright © Cambridge University Press 2010

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