BackgroundExposure to early life adversity (ELA) has been identified as a major risk factor in the development of major depressive disorder (MDD). It is hypothesized that a mediating mechanism may be environmentally induced alterations in gene function. In our REDEEM (Research in depression: endocrinology, epigenetics and neuroimaging) project we are examining possible epigenetic difference in some previously investigated target genes relevant to depression. To this end, methylation of the following genes were measured: NR3C1 (HPA axis), SLC6A4 (serotonin neurotransmitter function), and CD3ɛ (T cell receptor gene). We also looked at possible trans-generational transmission of epigenetic markers in a mother-baby sample.MethodsDNA was isolated from depressed patients and controls and babies and a portion of the above genes, encompassing our regions of interest, were amplified by PCR. Percentage methylation levels were measured by pyrosequencing. mRNA was also measured for some gene products to see if function was related to methylation. HPA axis function was measured with serial saliva samples throughout the day.Resultsto date: Methylation was increased in the CD3ɛ promoter in depressed subjects relative to controls. In the total group, those exposed to ELA had significantly increased methylation at this site. Levels of CD3ɛ mRNA levels were inversely related to methylation. There were some relationships between maternal ELA and baby methylation at the sites examined.ConclusionsConsistent with an allostatic model of ELA damage, our findings suggest an alteration in epigenetic function in acquired immunity and the HPA axis, mediated by ELA. Findings will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice