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- Tay, Nicole, et al.
(författare)
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Allele-Specific Methylation of SPDEF : A Novel Moderator of Psychosocial Stress and Substance Abuse
- 2019
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Ingår i: American Journal of Psychiatry. - : AMER PSYCHIATRIC PUBLISHING, INC. - 0002-953X .- 1535-7228. ; 176:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population.Methods: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study.Results: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use.Conclusions: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
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| 2. |
- Özel, Fatih, et al.
(författare)
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DNA methylation at DLGAP2 and risk for relapse in alcohol dependence during acamprosate treatment
- 2024
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Ingår i: Drug And Alcohol Dependence. - : Elsevier. - 0376-8716 .- 1879-0046. ; 256
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol use disorders are prevalent mental disorders with significant health implications. Epigenetic alterations may play a role in their pathogenesis, as DNA methylation at several genes has been associated with these disorders. We have previously shown that methylation in the DLGAP2 gene, coding for a synaptic density protein, is associated with alcohol dependence. In this study, we aimed to examine the association between DLGAP2 methylation and treatment response among patients undergoing acamprosate treatment. Methods: 102 patients under acamprosate treatment were included. DNA methylation analysis at DLGAP2 was performed by bisulfite pyrosequencing at the start and after 3 -month treatment. Treatment outcomes were having a relapse during the treatment and severity of craving at the end of three months. Cox proportional hazard and linear regression models were performed. Results: Patients whose methylation levels were decreased during the treatment showed an increased risk for relapse within three months in comparison to the ones without methylation change (hazard ratio [HR]=2.44; 95% confidence interval [CI]=1.04, 5.73; p=0.04). For the same group, a positive association for the severity of craving was observed, yet statistical significance was not reached (beta=2.97; 95% CI= -0.41, 6.34; p=0.08). Conclusion: We demonstrate that patients whose DLGAP2 methylation levels decrease during acamprosate treatment are more likely to relapse compared to the ones without changes. This is in line with our previous findings showing that DLGAP2 methylation is lower in alcohol dependent subjects compared to controls, and might suggest a role for changes in DLGAP2 methylation in treatment response.
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