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, 41 (5), 997-1007

Epigenetic and Inflammatory Marker Profiles Associated With Depression in a Community-Based Epidemiologic Sample

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Epigenetic and Inflammatory Marker Profiles Associated With Depression in a Community-Based Epidemiologic Sample

M Uddin et al. Psychol Med.

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.

Figures

Fig. 1
Fig. 1
Number of methylated and umethylated genes according to depression status. White indicates the genes uniquely methylated or unmethylated among individuals with lifetime depression, light grey indicates the genes uniquely methylated or unmethylated among individuals without lifetime depression, and dark grey indicates the genes commonly methylated or unmethylated in both groups. Methylated genes were defined as those genes with average β values of >0.8, and unmethylated genes were defined as those genes with average β values of <0.2.
Fig. 2
Fig. 2
Box plot of log-transformed interleukin (IL)-6 and C-reactive protein (CRP) serum levels in those with versus without lifetime depression. Shown are the log-transformed median IL-6 and CRP levels in each group (black horizontal bar) and also the range of the values, with the top and bottom whiskers representing the maximum and minimum values, respectively.

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