The Epigenetics of Psychosis: A Structured Review with Representative Loci
Abstract
:1. Introduction
2. MCHR1
2.1. Background for Environmental Impacts on the MCH System and Findings Relevant to Psychosis
2.2. Genetic Linkage and Differential Methylation of MCHR1 Identified for Schizophrenia and Bipolar Disorder with Psychosis
3. AKT1
3.1. Background on Cannabis-Induced Psychosis and the AKT1 Gene as a Model System for This Environmental Effect
3.2. Genetic Linkage of AKT1 to Psychotic Disorders, Gene-Environment Interaction with Cannabis Use and Potentially Relevant Methylation of AKT1 Identified
4. TDO2
4.1. Background on Relevance of the Kynurenine Pathway to Psychosis and the Response of the TDO2 Gene to Relevant Environmental Stimuli
4.2. Genetic Association Study Results for TDO2 in Schizophrenia and Bipolar Disorder with Psychosis, Key Regulatory Sites within the Gene, and Potentially Relevant Methylation Induced by Stress
5. Discussion
6. Acronyms, Their Description and Any Associated Websites Used in This Review
Funding
Conflicts of Interest
References
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Important environmental cue reviewed | Temperature, changes with season and latitude |
Direction of effect | Cold temperature stimulates expression of peptide agonist; MCHR1 controls thermo-regulation to lower body temperature and conserve BAT |
Risk of schizophrenia (scz) consistent with known gene function? | Yes:
|
Strength of genetic association | Moderate: 4 positive studies; and 1 positive when part of a complex genotype; contributes to PRS; the alleles conferring risk depend on the population |
Epigenetic data of relevance? | Yes:
|
Consistency of gene expression data | One study: gene expression decreased in scz, but may be confounded by smoking based on methylation pattern identified in smokers |
Important environmental cue reviewed | Cannabis use |
Direction of effect | Cannabis use predicted to inactivate AKT1 thru increased dopaminergic signaling, though animal data yields mixed results |
Risk of schizophrenia (scz) consistent with known gene function? | Yes: schizophrenia is associated with increased dopaminergic tone, which should inactivate AKT1 via DRD2 agonists; drugs that are antagonists for DRD2 exert an antipsychotic effect |
Strength of genetic association | Weak as a single locus: studies showing association as well as many showing lack of association; however, contributes to PRS |
Epigenetic data of relevance? | Yes:
|
Consistency of gene expression data | Mixed results for scz and related disorders Expression: Some studies show decreased gene expression, some no change and some increased expression; variability could be attributable to the effect of smoking seen in methylation data |
Important environmental cue reviewed | Stress |
Direction of effect | Stress is predicted to increase expression of gene via the established effect of glucocorticoids to stimulate TDO2 mRNA expression |
Risk of schizophrenia (scz) consistent with known gene function? | Yes:
|
Strength of genetic association | Weak as a single locus: one study showing association only as part of complex genotype; however, contributes to PRS |
Epigenetic data of relevance? | Yes:
|
Consistency of gene expression data | Consistent:
|
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Miller, C.L. The Epigenetics of Psychosis: A Structured Review with Representative Loci. Biomedicines 2022, 10, 561. https://doi.org/10.3390/biomedicines10030561
Miller CL. The Epigenetics of Psychosis: A Structured Review with Representative Loci. Biomedicines. 2022; 10(3):561. https://doi.org/10.3390/biomedicines10030561
Chicago/Turabian StyleMiller, Christine L. 2022. "The Epigenetics of Psychosis: A Structured Review with Representative Loci" Biomedicines 10, no. 3: 561. https://doi.org/10.3390/biomedicines10030561
APA StyleMiller, C. L. (2022). The Epigenetics of Psychosis: A Structured Review with Representative Loci. Biomedicines, 10(3), 561. https://doi.org/10.3390/biomedicines10030561