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. Author manuscript; available in PMC: 2017 Sep 1.
Published in final edited form as: Neurosci Biobehav Rev. 2016 Jun 18;68:474–488. doi: 10.1016/j.neubiorev.2016.06.010

Table 3.

Effects of mood stabilizers on DNA methylation

Drug Gene Disease/model Method Main effects Reference
Lithium 5mC and 5hmC Rat primary cortical neurons Immunocytochemis try Prevention of rotenone-induced increase in DNA methylation. Scola et al., 2014
Lithium BDNF PBMCs from BD patients MSP Reduction of BDNF methylation. D’Addario et al., 2012
Lithium BDNF PBMCs from BD patients MSP Reduction of BDNF methylation. Dell’Osso et al., 2014
Lithium Bdnf Rat hippocampal neurons MSP Hypomethylation of Bdnf exon IV promoter. Dwivedi and Zhang, 2014
Lithium Genome-wide methylation SK-N-SH cells Infinium HumanMethylation 27 Hypermethylation of 345 genes and hypomethylation of 138 genes. Asai et al., 2013
Lithium Global methylation Lymphoblasts from BD patients ELISA No effect on global methylation in patients (it remained decreased compared to controls after treatment). Rescue of methylation levels in relatives. Huzayyin et al., 2014
Lithium Igf2, Igf2r, H19 Mouse ESCs Bisulfite sequencing Hypomethylation of imprinted control regions via Dnmr3a2. Popkie et al., 2010
Valproate BDNF PBMCs from BD patients MSP Reduction of BDNF methylation. D’Addario et al., 2012
Valproate BDNF PBMCs from BD patients MSP Reduction of BDNF methylation. Dell’Osso et al., 2014
Valproate Genome-wide methylation SK-N-SH cells Infinium HumanMethylation 27 Hypermethylation of 64 genes and hypomethylation of 36 genes. Asai et al., 2013
Valproate Global methylation Primary rat astreocyte LUMA Global hypomethylation. Perisic et al., 2010
Valproate Glt-1 Primary rat cortical astrocyte Bisulfite sequencing Demethylation of Glt-1 promoter. Perisic et al., 2010
Valproate p21 Mouse hippocampal cells PCR and restriction enzymes analysis Demethylation of the distal region of p21. Aizawa and Yamamuro, 2015
Valproate RELN Mouse striatum (frontal cortex) 5-methyl CpG ChIP Decrease of RELN methylation after treatment to increase DNMT activity. Dong et al., 2008
Carbamazepine Genome-wide methylation SK-N-SH cells Infinium HumanMethylation 27 Hypermethylation of 64 genes and hypomethylation of 14 genes. Asai et al., 2013
Lamotrigine Global methylation Primary rat cortical astrocyte LUMA No changes in DNA methylation. Perisic et al.,

BD – bipolar disorder; Igf2 - insulin-like growth factor 2; Igf2r - insulin-like growth factor 2 receptor; HTR2A – serotonin receptor 2A; BDNF – brain-derived neurotrophic factor; 5mC – 5-methylcytosine; 5-hmC – 5-hydroxymethylcytosine; SLC6A4 - solute carrier family 6 (neurotransmitter transporter, serotonin) member 4; RELN - reelin; Glt-1 - glutamate type I transporter; LUMA - luminometric methylation analysis; MSP – methylation-specific PCR; PBMC – peripheral blood mononuclear cells; ChIP – chromatin immunoprecipitation.