In some cases, scientists are able to trace the earliest beginnings of disease to adverse life experiences, particularly those occurring in childhood. A new study uncovers the metabolic signature of one form of illness that may occur in childhood: depression. Episodes of major depression, the researchers found, change the amount of mitochondrial DNA as well as the length of telomeres in sufferers.

Sometimes called the cell's powerhouse, a mitochondrion is a membrane-bound structure within a cell that converts the energy derived from food into a form that cells can use. And, while most DNA is packaged within chromosomes inside the nucleus, mitochondria have a small amount of their own DNA. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, just as plastic tips protect the ends of shoelaces.

“Our most notable finding is that the amount of mitochondrial DNA changes in response to stress,” Dr. Jonathan Flint, a professor at the University of Oxford, said in a press release. He further explained how an increase in mitochondrial DNA would indicate a change not only in the mitochondria itself but also in the overall cellular energetics. And so this mood disorder may more properly be viewed as a disturbance of cellular energetics.

Childhood Adversity

Flint and his colleagues made this discovery when searching for genes that increase depression risk. Specifically, they examined a study of thousands of Chinese women, which included participants who had experienced recurrent major depression episodes along with healthy volunteers. Many of the depressed women also had experienced childhood adversity, including sexual abuse. Upon examining and comparing the samples from these two groups, the researchers discovered something surprising.

The samples received from women with a history of stress-related depression — those who had experienced childhood adversity — contained more mitochondrial DNA than the samples from healthy women.

"We were surprised," said Flint, "so surprised it took us a long time to convince ourselves it was real."

Next, the researchers evaluated and compared telomere length within the women’s samples. These caps at the ends of chromosomes — just repeated DNA sequences, in actuality — are known to shorten with each cell division (and so with age). Because changes in metabolism are known to alter the rate of aging, the researchers wondered whether depression might similarly change telomere length.

Sure enough, the depressed women had shorter telomere length compared to the healthy volunteers.

Finally, Flint and his colleagues decided to test these results in laboratory mice. Placing them through four weeks of stress, the researchers proved not only that stress caused molecular changes, but also these changes were partly reversible if they administred the stress hormone corticosterone. For this reason, Flint believes depression might be a metabolic reaction to stress.

Having taken a snapshot of the relationship between molecular markers and depression, Flint and his colleagues now "want to know how they change over time — before, during, and after a depressive illness."

In other words, if molecular changes do serve as biomarkers of stress, the researchers believe it could be possible to use a decline in mitochondrial DNA levels as an indicator of success following treatment for depression. Someday, too, a molecular signature might be a preventive clue so that doctors might help someone who experienced childhood adversity from suffering future physical illnesses.

Source: Cai N, Chang S, Li Y, et al. Molecular signatures of major depression. Current Biology. 2015.