P11 is a member of the S100 family of calcium effector proteins. Recent work suggests that p11 is necessary for antidepressant action since cortex-specific deletion of p11 abolishes behavioral responses to serotonin-specific reuptake inhibitor antidepressants (SSRIs) in rodent studies. The molecular mechanisms that govern the interaction between p11 and antidepressant response are still unclear.
In this study Melas and colleagues report that decreased levels of p11 were associated with higher DNA methylation in the promoter region of the p11 gene, in the prefrontal cortex of the Flinders Sensitive Line rodent model of depression. This hypermethylated pattern was reversed to normal (as defined by the control line) after chronic administration of the SSRI escitalopram. Escitalopram-induced hypomethylation was associated with both an increase in p11 gene expression and a reduction in messenger RNA levels of two enzymes known to maintain DNA methylation in adult forebrain neurons (DNA methyltransferases Dnmt1 and Dnmt3a). The authors concluded that the p11 gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment.
Melas PA, Rogdaki M, Lennartsson A, Björk K, Qi H, Witasp A, Werme M, Wegener G, Mathé AA, Svenningsson P, Lavebratt C: Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression. Int. J. Neuropsychopharmacol. 15(5):669-679 (2012).