Genetic Link Between Stress and Depression

Study Shows People With a Genetic Mutation May Be More Likely to Develop Depression

A gene that influences how the brain responds to stress may also play a key role in depression.

A new study shows people with a certain genetic mutation that causes them to produce less of the brain chemical neuropeptide Y (NPY) have a more intense negative emotional response to stress and may be more likely to develop depression than others.

Researchers found low levels of neuropeptide Y caused a stronger emotional response to negative stimuli and physiological response to pain in the brain, which may make people less resilient in the face of stress and more prone to depression.

"We've identified a biomarker -- in this case genetic variation -- that is linked with increased risk of major depression," says researcher Jon-Kar Zubieta, MD, PhD, professor of psychiatry and radiology at the University of Michigan, in a news release. "This appears to be another mechanism, independent of previous targets in depression research, such as serotonin, dopamine and norepinephrine."

Genetic Link to Depression

In three separate tests, researchers looked at the link between this genetic mutation and depression in 39 adults with depression and 113 healthy adults. The results are published in the Archives of General Psychiatry.

First, researchers measured the amount of NPY expression in each of the participants and used functional magnetic resonance imaging (fMRI) to measure the brain’s response to positive, neutral, or negative words like “hopeful,” “material,” or “murderer.”

The results showed people with low levels of this brain molecule had much more activity in an area of the brain associated with regulating emotions, the prefrontal cortex, than those with high levels.

Response to Stress

In a second experiment, researchers measured the response to a stressful event involving injecting saline solution into a jaw muscle, which produces moderate pain for about 20 minutes, but no lasting harm.

The study showed those with low neuropeptide Y rated their emotional response as more negative while anticipating the event before and immediately after the event while reflecting on their experience.

"This tells us that individuals with the risk-associated NPY gene variant tend to activate this key brain region more than other people, even in the absence of stress and before psychiatric symptoms are present," says researcher Brian Mickey, MD, PhD, assistant professor in the department of psychiatry at the University of Michigan Medical School, in the news release.

Finally, researchers found participants with this genetic variation were much more likely to have been diagnosed with depression than those without it.

"These are genetic features that can be measured in any person. We hope they can guide us toward assessing an individual's risk for developing depression and anxiety," Mickey says.