In patients with severe depression, cell aging is accelerated

Major depression (MDD) is related to premature death and is an independent risk factor for many diseases, especially diseases related to aging, such as cardiovascular disease, diabetes and Alzheimer's disease.

News from the official website of the University of California, San Francisco, April 6

According to a new study by the multidisciplinary research team of the University of California, San Francisco (UCSF), compared with the cells of healthy people without MDD, the cells of people with MDD have higher than expected methylation rates at specific sites in their DNA .

Methylation is a process in which DNA is chemically modified at a specific site, leading to changes in the expression of certain genes. The methylation of a particular set of genes, called the "DNA methylation clock", usually changes in predictable ways as people age, but the speed of these changes varies from person to person. The methylation patterns of individuals with MDD indicate that their cell age has accelerated on average relative to matched healthy controls.

In this study, published recently in Transitional Psychiatry, researchers used the "GrimAge" clock to analyze the DNA methylation patterns of blood samples from MDD patients. GrimAge is a cell-based methylation pattern. A mathematical algorithm for predicting the remaining life of an individual. Individuals with MDD disease show significantly higher GrimAge scores, which indicates an increased risk of death compared to healthy individuals of the same age—about two years on the GrimAge clock on average.

The research was published in Transitional Psychiatry (latest impact factor: 5.28) on April 6, 2021

Individuals with MDD showed no external signs of age-related pathology because they and healthy controls were screened for physical health before entering the study. Even taking into account lifestyle factors such as smoking and body mass index, methylation patterns associated with the risk of death still exist. These findings provide new insights into the increase in mortality and morbidity associated with the disease, indicating that there is a potential biological mechanism that accelerates cell senescence in some MDD patients.

"This is changing the way we understand depression, from a purely mental or psychiatric process limited to the brain to a systemic disease," said Katerina Protsenko, a medical student at UCSF University and the lead author of the study. This should fundamentally change the way we treat depression and how we think about it-as part of overall health."

MDD is one of the most common health problems in the world. According to the World Health Organization, about 300 million people (4.4% of the total population) suffer from some form of depression. MDD is associated with increased morbidity and mortality in patients with cardiovascular disease, diabetes, and Alzheimer's disease.

Dr. Owen Wolkowitz, one of the senior authors of the study and a member of the UCSF Weir Institute of Neuroscience and a professor of psychiatry, said: "A remarkable feature of depression is that even taking into account factors such as suicide and lifestyle habits, patients are age-related. The physical disease and early mortality rate are also unexpectedly high. This has always been a mystery, and it is also the reason why we look for signs of aging at the cellular level."

The researchers collected blood samples from 49 MDD patients who had not taken the drug before the study and 60 healthy control subjects of the same age. They used the GrimAge clock to analyze the methylation rates of the two groups. Although there are many lifespan algorithms based on methylation, GrimAge is the only one based exclusively on methylation patterns related to mortality.

Researchers say they don’t yet know whether depression causes methylation changes in some people, or whether depression and methylation are both related to another underlying factor. Some individuals may have a genetic tendency to produce specific methylation patterns in response to stress, but this has not been well studied. Changes in methylation patterns have previously been observed in patients with post-traumatic stress disorder.

Professor Owen Wolkowitz

Looking to the future, researchers hope to determine whether drug treatments or therapies can alleviate some of the methylation changes associated with MDD, hoping to normalize the aging process of the affected individuals before they progress. Although the GrimAge methylation clock is associated with mortality in other populations, no studies have yet to determine whether this methylation pattern can also predict mortality in MDD.

"As we continue our research, we hope to find out whether treating MDD with antidepressants or other treatments will change the methylation patterns. This will provide us with some signs that these patterns are dynamic and can be changed," UCSF Obstetrics and Gynecology Said Dr. Synthia Mellon, professor of the Department of Medicine and Reproductive Sciences and one of the senior authors of the study.

Via. Alan Toth