ArticleJournal of molecular psychiatry2013
Olanzapine induced DNA methylation changes support the dopamine hypothesis of psychosis.
Article in Journal of molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review.Molecular psychiatry · 2025Pooled it
- DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder.International journal of molecular sciences · 2018Pooled it
- Epigenetic Regulation of Inflammation by Dopamine in Primary Human Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- Comparing stem cells, transdifferentiation and brain organoids as tools for psychiatric research.Translational psychiatry · 2024Review
- Epigenetic Regulation in Schizophrenia: Focus on Methylation and Histone Modifications in Human Studies.Genes · 2024Review
- Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia.International journal of molecular sciences · 2024Review
- New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment.Frontiers in cellular neuroscience · 2024Review
- DNA Hyper-methylation Associated With Schizophrenia May Lead to Increased Levels of Autoantibodies.Schizophrenia bulletin open · 2024Article
- Genome-wide DNA methylation analysis in schizophrenia with tardive dyskinesia: a preliminary study.Genes & genomics · 2023Article
- Review
- Epigenetic Targets in Schizophrenia Development and Therapy.Brain sciences · 2023Review
- Dopamine-induced pruning in monocyte-derived-neuronal-like cells (MDNCs) from patients with schizophrenia.Molecular psychiatry · 2022Article
- Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022Article
- DNA Methylation Profiles of the DRD2 and NR3C1 Genes in Patients with Recent-Onset Psychosis.Disease markers · 2022Article
- Review
- The Cerebellar Dopaminergic System.Frontiers in systems neuroscience · 2021Review
- Skeletal muscle DNA methylation modifications and psychopharmacologic treatment in bipolar disorder.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2019Article
- Recent Progress in Pharmacogenomics of Antipsychotic Drug Response.Current psychiatry reports · 2018Review
- Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders.Brain sciences · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dopamine (DA) hypothesis of schizophrenia proposes the mental illness is caused by excessive transmission of dopamine in selected brain regions. Multiple lines of evidence, including blockage of dopamine receptors by antipsychotic drugs that are used to treat schizophrenia, support the hypothesis. However, the dopamine D2 receptor (DRD2) blockade cannot explain some important aspects of the therapeutic effect of antipsychotic drugs. In this study, we hypothesized that antipsychotic drugs could affect the transcription of genes in the DA pathway by altering their epigenetic profile.
methodsTo test this hypothesis, we examined the effect of olanzapine, a commonly used atypical antipsychotic drug, on the DNA methylation status of genes from DA neurotransmission in the brain and liver of rats. Genomic DNA isolated from hippocampus, cerebellum, and liver of olanzapine treated (n = 2) and control (n = 2) rats were analyzed using rat specific methylation arrays.
resultsOur results show that olanzapine causes methylation changes in genes encoding for DA receptors (dopamine D1 receptor, dopamine D2 receptor and dopamine D5 receptor), a DA transporter (solute carrier family 18 member 2), a DA synthesis (differential display clone 8), and a DA metabolism (catechol-O-methyltransferase). We assessed a total of 40 genes in the DA pathway and found 19 to be differentially methylated between olanzapine treated and control rats. Most (17/19) genes showed an increase in methylation, in their promoter regions with in silico analysis strongly indicating a functional potential to suppress transcription in the brain.
conclusionOur results suggest that chronic olanzapine may reduce DA activity by altering gene methylation. It may also explain the delayed therapeutic effect of antipsychotics, which occurs despite rapid dopamine blockade. Furthermore, given the common nature of epigenetic variation, this lends insight into the differential therapeutic response of psychotic patients who display adequate blockage of dopamine receptors.
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Registered trials
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