Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts


It is well established that people who suffer from serious mental illness are at higher risk of experiencing physical health problems, in addition to the psychological distress and functional impairment caused by their mental illness. This can result in a greater disease burden and much shorter lifespan. Despite widespread awareness of this phenomenon, treatment efforts focusing on this highly disadvantaged population have been largely inadequate. To address this issue, there is a need to explore the links between biological and lifestyle factors and poor health outcomes in individuals with mental illness. Such research is essential for identifying effective interventions to improve health and quality of life in this population.

Recent work has attempted to gauge the health effects of mental illnesses by measuring epigenetic aging (EA). EA is an emerging approach to studying the impact of intrinsic and extrinsic factors on health, and is more closely related to overall health status and cellular senescence than chronological age. Accelerated biological aging, indicative of poor health status can be deduced when estimated biological age exceeds chronological age. Several “epigenetic clocks” designed to measure EA have been proposed, with many of these measures predicting chronological age, morbidity, and excess mortality. However, correlations among EA measures are weak, indicative of several different processes underpinning biological aging, with different EA estimators putatively reflecting different aspects of the multifaceted aging process. Lu et al. recently presented the “DNAm GrimAge” EA measure, which is based on consolidated surrogate DNA methylation levels used to estimate plasma protein levels. The GrimAge algorithm has been demonstrated to be a strong predictor of lifespan, superior to all other methods in prediction of time-to-death, time-to-cancer, and time-to-coronary disease in three validation datasets comprising over 7,000 array measurements. In addition, GrimAge is strongly correlated to radiology-based estimates of excess visceral fat and a comorbidity index.

A new study published in Translational Psychiatry sheds light on excess aging in patients with Emotional unstable personality disorder (EUPD) with prior suicide attempts. EUPD, previously known as borderline personality disorder, is a mental disorder characterized by persistent patterns of unstable and intensive interpersonal relationships, efforts to avoid abandonment, identity disturbance, and self-destructive behavior. EUPD can cause significant impairment and disease burden, and is associated with a wide variety of medical conditions, poor health habits, and high mortality rates. Biological mechanisms underlying emotional instability in EUPD include abnormalities in the stress regulatory hypothalamic-pituitary-adrenal axis, which has both functional and epigenetic alterations. The study employed the GrimAge algorithm to investigate the relationship between epigenetic age acceleration (EAA), defined as the difference between a person's chronological age and their estimated age based on DNA methylation, and EUPD. Results showed that individuals with EUPD had higher EAA than healthy controls. Additionally, tobacco use was found to be a significant predictor of accelerated aging in individuals with EUPD. Users of tobacco had an EAA of 10.74 years, compared to non-users who had an EAA of only 6 years.

The study is significant because it challenges the assumption that factors like previous substance abuse or exposure to violence would be the main predictors of excess morbidity and mortality in patients with EUPD. Instead, the study found that tobacco use had the largest effect on excess aging among patients with EUPD, highlighting the importance of addressing somatic health conditions in this population.

These findings have important implications for public health efforts to reduce excess somatic morbidity and non-suicidal mortality in patients with EUPD. Specifically, targeted smoking cessation interventions across the lifespan have the potential to be low-cost and effective ways to reduce excess aging and improve overall health outcomes for these patients.

The study has several limitations, including its cross-sectional design, which precludes causal inference. Longitudinal studies are needed to investigate the temporal relationship between EUPD and EAA, and to determine whether interventions targeting EUPD symptoms can reduce EAA and improve health outcomes. The study also had a relatively small sample size, and larger studies are needed to confirm the findings and explore potential moderators of the relationship between EUPD and EAA. Furthermore, the study only included patients with EUPD, so it is unclear whether these findings would generalize to other patient populations.

In conclusion, the study highlights the need for healthcare providers and public health officials to prioritize somatic health and smoking cessation efforts in patients with EUPD. By reducing tobacco use and improving somatic health conditions, we can improve health outcomes and reduce excess morbidity and mortality in this vulnerable patient population.

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