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Updated: Oct 9, 2025
Targeted DNA Methylation Analysis by Next-generation Sequencing
Published on: February 24, 2015
Comprehensive DNA Methylation Analysis of Human Neuroblastoma Cells Treated With Haloperidol and Risperidone
Jianbin Du1, Yutaka Nakachi1, Tomoki Kiyono2
1Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Abstract:
Accumulating evidence suggests that the epigenetic alterations induced by antipsychotics contribute to the therapeutic efficacy. However, global and site-specific epigenetic changes by antipsychotics and those shared by different classes of antipsychotics remain poorly understood. We conducted a comprehensive DNA methylation analysis of human neuroblastoma cells cultured with antipsychotics. The cells were cultured with low and high concentrations of haloperidol or risperidone for 8 days. DNA methylation assay was performed with the Illumina HumanMethylation450 BeadChip. We found that both haloperidol and risperidone tended to cause hypermethylation changes and showed similar DNA methylation changes closely related to neuronal functions. A total of 294 differentially methylated probes (DMPs), including 197 hypermethylated and 97 hypomethylated DMPs, were identified with both haloperidol and risperidone treatment. Gene ontology analysis of the hypermethylated probe-associated genes showed enrichment of genes related to the regulation of neurotransmitter receptor activity and lipoprotein lipase activity. Pathway analysis identified that among the DMP-associated genes, SHANK1 and SHANK2 were the major genes in the neuropsychiatric disorder-related pathways. Our data would be valuable for understanding the mechanisms of action of antipsychotics from an epigenetic viewpoint.
Insights
Antipsychotics like haloperidol and risperidone induce DNA methylation changes, primarily hypermethylation, impacting neuronal functions and neuropsychiatric pathways. These epigenetic alterations offer insights into antipsychotic mechanisms.
Area of Science:
- Neuroscience
- Epigenetics
- Pharmacology
Background:
- Epigenetic alterations by antipsychotics are linked to therapeutic effects.
- Understanding global and specific epigenetic changes induced by different antipsychotic classes is limited.
Purpose of the Study:
- To comprehensively analyze DNA methylation changes induced by antipsychotics.
- To identify common epigenetic alterations across different antipsychotic classes.
Main Methods:
- Human neuroblastoma cells were treated with haloperidol or risperidone at varying concentrations for 8 days.
- DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip array.
- Gene ontology and pathway analyses were performed on differentially methylated probes (DMPs).
Main Results:
- Both haloperidol and risperidone induced similar DNA methylation changes, predominantly hypermethylation.
- A total of 294 DMPs were identified, with 197 showing hypermethylation and 97 hypomethylation.
- Hypermethylated genes were enriched in neurotransmitter receptor and lipoprotein lipase activity pathways, with SHANK1 and SHANK2 highlighted in neuropsychiatric pathways.
Conclusions:
- Antipsychotics induce significant, shared DNA methylation changes, particularly hypermethylation, in neuronal cells.
- These epigenetic modifications are associated with key neuronal functions and neuropsychiatric disorder pathways.
- The findings provide an epigenetic perspective on antipsychotic mechanisms of action.
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