Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder.

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.

Treatment-associated mRNA co-expression changes in monocytes of patients with posttraumatic stress disorder.

PTSD is a prevalent mental disorder that results from exposure to extreme and stressful life events and comes at high costs for both the individual and society. Therapeutic treatment presents the best way to deal with PTSD-the mechanisms underlying change after treatment, however, remain poorly understood. While stress and immune associated gene expression changes have been associated with PTSD development, studies investigating treatment effects at the molecular level so far tended to focus on DNA methylation. Here we use gene-network analysis on whole-transcriptome RNA-Seq data isolated from CD14+ monocytes of female PTSD patients (N = 51) to study pre-treatment signatures of therapy response and therapy-related changes at the level of gene expression. Patients who exhibited significant symptom improvement after therapy showed higher baseline expression in two modules involved in inflammatory processes (including notable examples IL1R2 and FKBP5) and blood coagulation. After therapy, expression of an inflammatory module was increased, and expression of a wound healing module was decreased. This supports findings reporting an association between PTSD and dysregulations of the inflammatory and the hemostatic system and mark both as potentially treatment sensitive.