ABSTRACT
BACKGROUND: Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken. METHODS: As markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates. RESULTS: The majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain. CONCLUSIONS: The present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.
ABSTRACT
Epigenetic alterations are regarded as a potential mechanism mediating the effects of environmental risk factors on vulnerability for a range of mental health problems. Recent studies have addressed the question whether DNA methylation patterns predict the outcome of psychological interventions and whether treatment effects might be associated with changes of DNA methylation. We assessed phobic fear symptoms, treatment-relevant traits and treatment response in 308 adults free of psychotropic medication - highly fearful of either spiders, blood-injury-injections, dental-treatments or heights - all subjected to highly standardized exposure-based one-session fear treatment. DNA methylation level of the promotor region of the serotonin transporter gene (SLC6A4) was assessed in either saliva samples (spider and dental treatment fear cohorts) or oral mucosa (BII, heights) to check whether possible effects are independent of the surrogate tissue examined. Moreover, in order to examine possible DNA methylation by genotype effects, patients were assessed for genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR). DNA methylation levels were neither associated with pre-treatment fear levels, treatment relevant traits or treatment outcome data even when allelic variation of the 5HTTLPR was considered. Overall DNA methylation levels were higher in saliva samples compared to buccal samples. In saliva samples there was a small pre- to post-treatment increase in DNA methylation, which, however, was also not associated with the investigated phenotypes. We conclude that DNA methylation of SLC6A4 is no suitable biomarker for response efficacy to highly standardized one-session exposure-based fear treatments.
Subject(s)
DNA Methylation , Serotonin Plasma Membrane Transport Proteins , Adult , Humans , DNA Methylation/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Fear/psychology , Genotype , AllelesABSTRACT
Data collection in remote and field settings gains importance and popularity in stress research. Accordingly, existing stress induction paradigms have been successfully adapted to remote and field settings. However, guidelines for the comprehensive assessment of biomarkers such as salivary alpha-amylase (sAA) have yet to be sufficiently established for such contexts. In remote and field settings, swift freezing of saliva samples is not always possible, and samples must be returned to the laboratory for further processing. The current study investigated the robustness of sAA activity against external factors that may affect measurements obtained from saliva samples collected in field and remote settings. We compared sAA activity of samples that were stored in different vials (Salivettes® and Eppendorf® vials) and that were exposed to (1) up to three cycles of freezing and thawing, (2) different temperatures (4 °C, 20 °C, 30 °C, and 40 °C) for 3, 7, 14, or 28 days, or that were (3) sent via postal delivery. Results indicate sAA activity to be susceptible across different temperatures, different time intervals, and different vials. As a systematic pattern, sAA activity seems to decrease in treated samples with this effect being potentiated by more extreme conditions such as higher temperatures and longer time intervals. To conclude, sAA data collected in remote or field settings could be affected systematically by various external variables. Future studies collecting sAA should take factors influencing the durability and stability of sAA into account to ensure reliable and valid measurements of salivary data.