Epigenetic Side Effects of Common Pharmaceuticals

[jdmiller1]

Lots of good info in this article. The gist of it is that there are persistent changes to gene expression that encodes the 5ht1a receptor.

Besides stimulants, SSRI antidepressants have been shown to cause long-term alterations in gene expression, presumably result- ing from chronic elevation of serotonin (5-HT) neurotransmission in the brain [104]. For example, chronic treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5HT1A receptors even after removal of the SSRI [105]. These long-term adaptive changes in 5-HT receptors, as well as more complex, global changes, are likely to be mediated through altera- tions of gene expression [106–110]. Some of these gene expression changes are a result of altered DNA structure caused by chromatin remodeling [111,112], specifically epigenetic modification of his- tones [113] and gene silencing by DNA methylation due to in- creased expression of the methyl binding proteins MeCP2 and MBD1 [114] Induction of the aforementioned methyl binding pro- teins was accompanied by enhanced HDAC2 mRNA synthesis, and decreased amounts of histone H3 were detected in three serotonin projection areas: the caudate-putamen, the frontal cortex, and the dentate gyrus of the hippocampus. Taken together, it appears that increased MDB1, MeCP2 and HDAC2 expression and recruitment to DNA plays a role in the regulation of histone acetylation and repression of gene expression is a generalized response to fluoxetine.

http://www.medicinabiomolecular.com.br/ ... g-0043.pdf