We read with great interest the recent article by Brown et al1 about the impact of prenatal elevated homocysteine levels on the risk of schizophrenia. The presented findings are striking and of high importance for a better understanding of the pathogenesis of schizophrenia.
The authors hypothesize that homocysteinemia may elevate the risk of schizophrenia via an action on the delivery of oxygen. This may be one possible and important explication to take into consideration. However, another important pathophysiological mechanism should be taken into account when discussing the presented findings. Homocysteine is known to act as a methyl-donator when activated to S-adenosyl-methionine and by this way influences global and gene promoter-specific DNA methylation.2,3 There is mounting evidence that altered promoter DNA methylation could play a substantial role in mediating differential regulation of genes and in facilitating short-term adaptation in response to the environment in different psychiatric disorders, including schizophrenia.2,4,5 Furthermore, heredity of global and promoter-specific DNA methylation has been shown in various studies.6 Changes in epigenetic DNA methylation due to homocysteinemia may therefore be one possible explication for the results presented by Brown and colleagues.1 Especially when considering the possible impact of changes in DNA methylation, which alters gene expression, it is feasible that elevated homocysteine levels may influence fetal neurogenesis due to epigenetic mechanisms.
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