Table 3.
Studies of Epigenome-wide Association.
| Study | EWAS Method | Objective | Main Finding (s) |
|---|---|---|---|
| Burghardt et al.a [22] | Illumina 450K | Identify methylation associated with antipsychotic-induced insulin resistance | Two sites associated with AAP-induced insulin resistance after correction for multiple testing. The top site was in an intergenic region and the second site was in the FAR2 gene. The FAR2 site was replicated in an additional sample. |
| Burghardt et al. [23] | Illumina 450K | Determine the methylation profile related to metabolic syndrome in SCZ patients on antipsychotics | Sites within five genes found to be associated with metabolic syndrome and the top pathway from a bioinformatic analysis was the Wnt/β-catenin pathway. Additionally, sex-specific sites associated with metabolic syndrome were also identified. Validation occurred in additional sample set for two genes (CDH22 and MAP3K13 genes). |
| Houtepen et al. [30] | Illumina 27K (n=122) and 450K (n=50) | Identify changes based on AAP and mood stabilizer use | No individual methylation sites were significant after multiple testing correction. Methylation changes in pathways related to neurogenesis, embryonic function, regulatory, and immune function were associated with quetiapine treatment. |
| Kinoshita et al. [31] | Illumina 450K | Identify changes after 1 year of clozapine treatment | 29,134 CpG sites showed significant changes in DNA methylation. A higher number of sites had decreased DNA methylation compared to increased methylation. These sites were associated with the cell substrate adhesion and cell matrix adhesion pathways. A site within the CREBBP gene was the sole site associated with psychotic symptom changes after correction for multiple testing. |
| Mill et al. [35] | In-house CpG island microarray | Determine DNA methylation profiles in major psychosis and with lifetime antipsychotic treatment | Male patients with SCZ had lower methylation in the MAP2K1 gene which correlated with lifetime antipsychotic use. A similar trend was observed in female patients with SCZ but this did not remain significant with a correction for multiple testing. Overall, psychiatric patients had differential methylation in “Mitochondrial” pathways. |
| Rukova et al. [39] | Agilent Human DNA Methylation Microarray | Identify the DNA methylation profiles after prospective treatment with antipsychotics | Differentially methylated regions differed from controls before and after treatment and were also dependent on sex and remission status. |
Details of six studies that analyzed epigenome-wide methylation arrays in antipsychotic-treated patients with schizophrenia or bipolar disorder. AAP = atypical antipsychotic; CDH22 = Cadherin 22; CREBBP = CREB Binding Protein; EWAS = Epigenome-Wide Association Study; FAR2 = Fatty acyl CoA reductase; MAP3K13 = Mitogen-Activated Protein Kinase Kinase Kinase 13; MAP2K1 = Mitogen-Activated Protein Kinase Kinase 1; SCZ = schizophrenia