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

group. No discrepancies in methylation or expression were Moreover, research indicates that drug-seeking behavior
detected in the various other dopamine receptors that were and excessive alcohol drinking are often comorbid
examined. In addition, Groleau et al. found that women with depressive-like symptoms and behaviors. These
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diagnosed with bulimia spectrum disorder, particularly behaviors are frequently observed in individuals who faced
those with borderline personality disorder, demonstrated adversity in their early life and are important features found
significant elevations in DRD2 DNA methylation levels in animal models of early life stress exposure. In fact,
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than women with no eating disorders. Moreover, women Guo et al. reported that, in rats, the rats subjected to MD,
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with a history of bulimia spectrum disorder and childhood chronic unpredictable stress (CUS), and a combination
sexual abuse showed increased DRD2 DNA methylation of both (MD/CUS) displayed increased levels of DRD2
compared to the group with no eating disorder history. promoter DNA methylation compared to normal controls.
These results suggest that individuals with bulimia The authors concluded that early-life MD increased
spectrum disorder experience an increase in DNA vulnerability to stress-induced depressive-like behavior
methylation of the DRD2 gene promoter, which may serve in adult rats. In line with the findings of Gondre-Lewis’s
as a stronger marker of comorbid psychopathology rather group, 141-143 increased methylation of the DRD2 promoter
than being a board correlate of eating disorders in general. gene in the ventral tegmental area may raise the risk of
depression and alcohol-seeking behavior. Furthermore,
5.1.7. Gambling Zhu et al. explored the effects of MD on adult rats’ spatial
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According to several studies, dopaminergic circuits may learning and memory, exploratory, and limbic activity, along
play a role in the pathophysiology of problematic gambling with their association with the expression of DAT, DRD1,
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behavior. 132-134 Hillemacher et al. reported that DNA DRD2, and DRD3 in the NAc. In addition, Zhu et al.
methylation patterns in the DRD2-gene were modified investigated the potential involvement of DNA methylation
with respect to abstinence over a 12-month or a 30-month in the regulation of DRD2 gene expression. Based on their
period. In addition, they observed increased levels of DNA work, only the DRD2 mRNA level was associated with
methylation in individuals who were non-abstinent and total distance. However, the expression of DNMT1 and 3
those who did not seek treatment. These findings suggest alpha (DNMT3A) and the methylated CpG levels in the
that altered DRD2 expression, resulting from variations in promoter region of the DRD2 gene were not significantly
DNA methylation, holds pathophysiological significance altered in the MD group compared to the control group.
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in lifetime pathologic gambling behavior. Functional differences may have occurred in other sites at
the DRD2 genes not included in the study, and/or other
5.1.8. Personality disorders epigenetic modifications were associated with DRD2 mRNA
Utilizing chimpanzees, which are known to exhibit five expression. Notwithstanding, it is possible that deficient
dimensions of personality (agreeableness, dominance, control screening and interpretation may have impacted
extraversion, openness, and reactivity/undependability), the association study, and further research with carefully
Staes et al. observed that DRD2 DNA methylation is most selected controls, not just MD, may alter these results.
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strongly linked to extraversion. In addition, they found
that varying DNA methylation levels at specific DRD2 sites 5.1.10. Social defeat stress
were linked to changes in extraversion in nursery-reared, In terms of social defeat stress, Zhu et al. reported that
but not mother-reared, individuals. These findings provide chronic social defeat stress regulates FOSB expression in the
further support for the importance of biological mother- NAc, which promotes the cell-type-specific accumulation
related rearing in early life. This work further suggests that of ΔFosB in the two MSN subtypes in this region. ΔFosB
early-life experiences can influence long-lasting behavioral is selectively induced in D1-MSNs in the NAc of resilient
effects, theoretically through epigenomic modification. mice and in D2-MSNs of susceptible mice. In this
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Accordingly, these results contribute to the increasing regard, Hamilton et al. reported that FOSB-targeted
body of research demonstrating the critical role of the histone acetylation in D2-MSNs or histone methylation
experience-dependent methylome in the development of in D1-MSNs promotes a stress-susceptible, depressive-
personality. 134,136-140 like phenotype, while histone methylation in D2-MSNs
or histone acetylation in D1-MSNs enhance resilience to
5.1.9. Maternal deprivation (MD) social stress as measured by social interaction behavior and
Gondre-Lewis’s group correctly points out that sucrose preference. Importantly, the study presented the
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stress experienced early in life can trigger a complex first evidence of targeting histone modifications specifically
neurochemical cascade, affecting the emotional and to genes and cells, simulating real-world transcriptional
addictive behaviors of adolescents and adults later in life. processes that regulate social defeat stress behavior.
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Volume 3 Issue 1 (2024) 10 https://doi.org/10.36922/gpd.1966