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

Abstract

BackgroundRecent 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.MethodUsing 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.ResultsUniquely 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.ConclusionsGenome-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.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…An inverse correlation between methylation of IL-6 CpGs and circulating IL-6 and CRP levels was reported in individuals with lifetime depression (Uddin et al 2011), but findings have yet to be replicated.…”

“…High CRP serum levels were identified as a risk factor for de novo depression in women (Pasco et al 2010), depression in men (Ford and Erlinger, 2004;Liukkonen et al 2006;Elovainio et al 2009;Vogelzangs et al 2012), atypical depression (Hickman et al 2014) and depressive symptoms (Uddin et al 2011), especially of the somatic type (Duivis et al 2013). Furthermore, life-time occurrence of multiple depressive episodes was associated with higher CRP levels (Copeland et al 2012).…”

Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting

“…Genotyping, targeted bisulfite pyrosequencing, and real-time RT-PCR has been successfully performed in the Wildman and Uddin laboratories 20,21,22,23 . Serum, isolated in parallel with the DNA isolation for both the Beadchip and genotyping analyses, was successfully analyzed for IL-6 and C-reactive protein activity 24 . T-cell subsets from the isolated PBMCs have been successfully analyzed by flow cytometry [25][26][27][28] …”

“…Although many of these techniques are available in the existing literature, our step-by-step compilation, including precisely timed alterations between each step, reflects an optimized, efficient protocol that successfully produces a variety of biologic specimens with a wide range of downstream applications, including DNA methylation, mRNA expression and immunological analysis. These specimens have already been tested in a variety of experiments, results of which have been published in peer-reviewed literature and/or presented at national meetings 11,20,21,23,24,29 . This protocol should thus be of interest to other investigators seeking to collect biological specimens in population-based studies similar to the DNHS.…”

Epigenetics and depression: return of the repressed

“…Suicide completers with MDD Global ↓and reorganisation in miRNA expression in MDD ↓21 miRNAs Uddin et al (2011) Blood MDD Altered DNA methylation pattern in MDD Xu et al (2010) Blood MDD Polymorphism in pre-miR30e associated with MDD and difficulties with the speed of perception and processing of auditory stimuli (Eranti et al, 2007;UK Ect Review Group, 2003). The precise mechanisms of action of ECT remain unknown but evidence in animal models suggests that treatment with ECS (electroconvulsive stimulation), the animal model equivalent of ECT, results in epigenetic modification of gene expression (Table 3).…”