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Gene & Protein in Disease Stress-induced epigenetics of the DRD2 gene

investigating epigenetic modifications to the DRD2 gene Funding
to directly illustrate the role of these epigenetic changes
in addiction-related behavioral abnormalities. At present, None.
there is a growing awareness regarding the utilization of Conflict of interest
various effector moieties to counteract these undesirable
negative epigenetic changes, as recently observed by Kenneth Blum holds patents, both domestic and foreign,
Pandey’s group in mitigating alcohol-induced anxiety. related to pro-dopamine regulation complexes and genetic
104
testing for addiction risk. Other authors declare no conflict
Experimentally, effector moieties are providing of interest.
unprecedented information relevant to not only mechanistic
insights but also to demonstrate the importance of removing Author contribution
these negative epigenetic insults, leading to the concomitant
attenuation of specific mRNA transcriptional expression, Conceptualization: Kenneth Blum
such as the DRD2 gene. One important unanswered question Writing – original draft: Kenneth Blum
Writing – review and editing: All authors
is whether induction, for example, of dopamine homeostasis,
would increase the conversion of post-transcriptional Ethics approval and consent to participate
histone methylation to acetylation. Our laboratory has been
developing a nutraceutical complex to gently induce pro- Not applicable.
dopamine regulation, potentially in both animal models Consent for publication
and humans. To answer this profoundly important question,
we advocate for the scientific community to perform the Not applicable.
necessary research in this arena.
Availability of data
9. Conclusion Not applicable.

The DRD2 gene has been extensively investigated in various
neuropsychiatric disorders. Numerous international References
studies have been performed since the initial association of 1. Domi E, Domi A, Adermark L, Heilig M, Augier E.
the DRD2 Taq A1 allele with severe alcoholism in 1990. In Neurobiology of alcohol seeking behavior. J Neurochem.
our opinion, the primary cause of negative reports regarding 2021;157(5):1585-1614.
the association of various DRD2 gene polymorphisms is the doi: 10.1111/jnc.15343
inadequate screening of controls, failing to eliminate many
hidden RDS behaviors. Moreover, pleiotropic effects of 2. Haass-Koffler CL, Magill M, Cannella N, et al. Mifepristone
as a pharmacological intervention for stress-induced
DRD2 variants have been observed in neurophysiological, alcohol craving: A human laboratory study. Addict Biol.
neuropsychological, stress response, social stress defeat, 2023;28(7):e13288.
MD, and gambling disorder contexts, where epigenetic
DNA methylation and negative histone post-translational doi: 10.1111/adb.13288
methylation have been identified, as discussed in this 3. Blum, K, Chen TJH, Meshkin B, et al. Manipulation
commentary. As of October 19, 2022, there are 70 articles of catechol-O-methyl-transferase (COMT) activity to
focusing on DNA methylation and 20 articles on histone influence the attenuation of substance seeking behavior,
methylation are listed in PUBMED. Importantly, Blum and a subtype of Reward Deficiency Syndrome (RDS), is
Noble characterized the DRD2 Taq A1 allele not as specific dependent upon gene polymorphisms: A hypothesis. Med
Hypotheses. 2007;69(5):1054-1060.
to alcoholism but as a generalized reward gene. Therefore,
it now behooves the field to find ways to either use effector doi: 10.1016/j.mehy.2006.12.062
moieties to edit the neuroepigenetic insults or possibly 4. Blum K, Trachtenberg MC, Elliott CE, et al. Enkephalinase
harness the idea of potentially removing negative mRNA- inhibition and precursor amino acid loading improves
reduced expression by inducing dopamine homeostasis. inpatient treatment of alcohol and polydrug abusers:
This represents a futuristic laudable goal. Double-blind placebo-controlled study of the nutritional
adjunct SAAVE. Alcohol. 1988;5(6):481-493.
Acknowledgments doi: 10.1016/0741-8329(88)90087-0
The authors appreciate the expert edits provided by 5. Blum K, Chen ALC, Chen TJH, et al. Activation instead
Margaret A. Madigan and the formatting provided by of blocking mesolimbic dopaminergic reward circuitry is
Danielle Kradin. a preferred modality in the long term treatment of reward

Volume 3 Issue 1 (2024) 12 https://doi.org/10.36922/gpd.1966