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Reportedly, no DNA methylation studies have been performed in relation to the antidepressant treatment. However, antidepressant treatment may affect gene expression at the DNMT level in brain.[@cit0021] Our results suggest that antidepressant treatment may affect DNA methylation, with antidepressant treatment increasing the methylation level of CDKN2A, DUSP6, SELENBP1 and CDK5R1 in the hippocampus of mice. Thus, we can conclude that an alteration in the expression of these genes is responsible for the observed changes in the methylation levels of CDKN2A, DUSP6, SELENBP1 and CDK5R1. However, it is not possible to exclude the methylation of other genes.

In conclusion, the main findings of this study, i.e., the reduced methylation level of CDKN2A and DUSP6, suggest that alterations in the methylation levels of these genes may have a role in the pathophysiology of depression. In addition, the increase in the methylation level of SELENBP1 and CDK5R1 in the antidepressant-treated mice may be related to the antidepressant effect of treatment. However, the results of this study should be interpreted with caution because of the relatively small sample size. Future studies with a large number of mice, and/or patients with depression are warranted. The mechanisms responsible for the changes in the methylation levels of the genes studied in this work may be related to the effects of the antidepressant treatment, as mentioned above.

The authors are thankful to Nadia Farrán-Valdés, Román Gómez-Ruiz and Karla Angosto-García for their invaluable technical support.

Abbreviations #s0005

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FST, forced swim test; CDKN2A, cyclin-dependent kinase inhibitor 2A

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