In summary, our data reveal increased site-specific methylation in the exon 1F NR3C1 promoter in suicide victims with a history of childhood abuse and suggest that there is a relationship between cytosine methylation, transcription factor binding and gene expression. Our results are consistent with evidence from studies using psychological autopsy methods40 and epidemiological longitudinal designs45, which suggest that suicide has a developmental origin. We acknowledge that such conclusions are based on samples that differ along a wide range of experiential and potentially genetic dimensions. Our data certainly do not exclude alternative mechanisms of vulnerability. Indeed, the challenge for the future is to understand how epigenetic variation overlaying that occurring in nucleotide sequence might explain the developmental origins of vulnerability for chronic illness. Our data are merely consistent with observations from animal studies investigating epigenetic regulation of the Nr3c1 gene and with the hypothesis that early life events can alter the epigenetic state of relevant genomic regions, the expression of which may contribute to individual differences in the risk for psychopathology.
