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


METHODS
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.
Uddin
M
M
Center for Social Epidemiology and Population Health, Department of Epidemiology, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA. uddinm@umich.edu
Koenen
K C
KC
Aiello
A E
AE
Wildman
D E
DE
de los Santos
R
R
Galea
S
S
D000328:Adult; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016000:Cluster Analysis; D019175:DNA Methylation; D003866:Depressive Disorder / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008824:Michigan / Q000453:epidemiology
D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein