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Heim, C. C.

Publications and source records attributed to Heim, C. C..

3 recordsLinked to original sources

Exposure to childhood adversity and adult alcohol, nicotine, and illicit drug use in Germany: a cross-sectional analysis of the German National Cohort (NAKO)

Rationale: Exposure to adversity in childhood and adolescence (i.e., "early-life stress"; ELS) is a well-established risk factor for substance use. Objectives: The aim of this study was to investigate associations between ELS exposure and substance use across subtypes of ELS, different substance classes, and behavioral profiles of substance use. Methods: In this cross-sectional study, we examined associations between ELS exposure and substance use in a population-based sample of 172,173 adults aged 19-74 years from the German National Cohort (NAKO). ELS exposure was assessed using the Childhood Trauma Screener. Substance use included nicotine, alcohol, and illicit drug use. Associations were examined using regression models evaluating overall ELS exposure, cumulative trauma load, and ELS subtypes. Latent class analysis (LCA) was conducted to identify substance use profiles. Results: ELS exposure was associated with higher odds of smoking, greater smoking severity, heavier alcohol consumption among drinkers, and higher odds of lifetime illicit drug use. Overall, the strongest associations were observed for opioid and stimulant use. Dose-response analyses revealed higher risk with increasing numbers of ELS subtypes. Abuse-related subtypes, particularly exposure to physical and sexual abuse, consistently showed strongest independent associations across substances, whereas neglect exhibited weaker, more variable associations. LCA identified four substance use profiles, with ELS exposure predicting membership in more severe polysubstance classes. Conclusions: ELS emerged as a robust risk factor for adult substance use, underscoring the need for trauma-informed approaches in clinical practice, public health, and policy to mitigate the long-term consequences of early adversity.

neuroscience↗

Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans

Epigenetic clocks are a common group of tools used to measure biological aging - the progressive deterioration of cells, tissues and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. We tested 284 distinct tissue samples from 83 individuals aged 9-70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age.

genomics↗

Cross-tissue comparison of telomere length and quality metrics of DNA among individuals aged 8 to 70 years

Telomere length (TL) is an important biomarker of cellular aging, yet its links with health outcomes may be complicated by use of different tissues. We evaluated within- and between-individual variability in TL and quality metrics of DNA across five tissues using a cross-sectional dataset ranging from 8 to 70 years (N=197). DNA was extracted from all tissue cells using the Gentra Puregene DNA Extraction Kit. Absolute TL (aTL) in kilobase pairs was measured in buccal epithelial cells, saliva, dried blood spots (DBS), buffy coat, and peripheral blood mononuclear cells (PBMCs) using qPCR. aTL significantly shortened with age for all tissues except saliva and buffy coat, although buffy coat was available for a restricted age range (8 to 15 years). aTL did not significantly differ across blood-based tissues (DBS, buffy coat, PBMC), which had significantly longer aTL than buccal cells and saliva. Additionally, aTL was significantly correlated for the majority of tissue pairs, with partial Spearmans correlations controlling for age and sex ranging from = 0.18 to 0.51. We also measured quality metrics of DNA including integrity, purity, and quantity of extracted DNA from all tissues and explored whether controlling for DNA metrics improved predictions of aTL. We found significant tissue variation: DNA from blood-based tissues had high DNA integrity, more acceptable A260/280 and A260/230 values, and greater extracted DNA concentrations compared to buccal cells and saliva. Longer aTL was associated with lower DNA integrity, higher extracted DNA concentrations, and higher A260/230, particularly for saliva. Model comparisons suggested that incorporation of quality DNA metrics improves models of TL, although relevant metrics vary by tissue. These findings highlight the merits of using blood-based tissues and suggest that incorporation of quality DNA metrics as control variables in population-based studies can improve TL predictions, especially for more variable tissues like buccal and saliva.

genomics↗