“Epigenetic changes are associated with depression. Some depressed patients have increased DNA methylation and decreased expression of the gene encoding BDNF, a secreted factor important for synaptic plasticity. Rein et al. found that some antidepressants inhibit epigenetic changes by causing a switch in chaperone binding to the DNA methyltransferase DNMT1. The chaperones FKBP51 and FKBP52 competed for binding to CDK5, a kinase that activates DNMT1. The authors found that cells from depressed patients or cultured mouse astrocytes exposed to the antidepressant paroxetine favored the FKBP51-CDK5 interaction, resulting in reduced activity of DNMT1 and DNA methylation, and increased the expression of BDNF. These effects of paroxetine on patient blood cells isolated before therapy correlated with a positive clinical response to antidepressants, suggesting that a simple blood test may aid in personalizing treatment for depression.”
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Gassen NC, Fries GR, Zannas AS, Hartmann J, Zschocke J, Hafner K, Carrillo-Roa T, Steinbacher J, Preißinger SN, Hoeijmakers L, Knop M, Weber F, Kloiber S, Lucae S, Chrousos GP, Carell T, Ising M, Binder EB, Schmidt MV, Rüegg J and Rein T: Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine. Sci. Signal. 8(404): ra119 (2015); DOI: 10.1126/scisignal.aac7695

http://www.ncbi.nlm.nih.gov/pubmed/26602018

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