Link between genes and depression

People who are genetically predisposed to produce lower amounts of a certain brain chemical that regulates appetite and stress may be at higher risk of severe depression, researchers say.

The findings should shed more light on how depression affects certain people more than others, and could help lead the way toward developing more individualised therapies, researchers at the University of Michigan said.

"We've identified a biomarker in this case genetic variation that is linked with increased risk of major depression," said senior study author Jon-Kar Zubieta, a professor of psychiatry and radiology.

"This appears to be another mechanism, independent of previous targets in depression research, such as serotonin, dopamine and norepinephrine."

People who produce lower amounts of the brain molecule neuropeptide Y (NPY) had "measurably stronger brain responses to negative stimuli and psychological responses to physical pain," the study said.

"They were also overrepresented in a population diagnosed with a major depressive disorder."

The study

The study, which appears in the Archives of General Psychiatry, used three different methods. First, researchers classified subject participants into three categories according to low, medium or high NPY expression.

Then, they used MRI (magnetic resonance imaging) to look at brain activity as the subjects viewed different words, some neutral (like "material"), some negative (like "murderer") and some positive (like "hopeful").

"In response to negative words, subjects in the low NPY group showed strong activation in the prefrontal cortex, which is involved with processing emotion, while subjects with high NPY demonstrated a much smaller response," the study said.

In the second trial, researchers looked at how subjects described their emotional state before and after a stress challenge in which saline solution was injected into their jaw muscles, causing moderate pain for about 20 minutes.


"Those in the low NPY group were more negative both before and after the pain, meaning they were more emotionally affected while anticipating the pain and while reflecting on their experience immediately afterward," it said.

Finally, researchers examined the NPY genotypes of people with major depressive disorders and found that, compared to a control group, people with low NPY were "overrepresented" in the group with depression.

"These are genetic features that can be measured in any person," said lead author Brian Mickey, an assistant professor in the Department of Psychiatry at the University of Michigan Medical School.

"We hope they can guide us toward assessing an individual's risk for developing depression and anxiety."

(Sapa, February 2011)

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