Gene linked to major depression identified

Tuesday, February 8, 2011

WASHINGTON - A gene that influences how the brain responds to stress may also play a key role in depression, according to a new study.

Numerous studies have shown that the brain molecule neuropeptide Y (NPY) helps to restore calm after stressful events.

However, a team of University of Michigan-led researchers has found that people whose genes predispose them to produce lower levels of NPY have a more intense negative emotional response to stress and may be more likely to develop a major depressive disorder.

They now hope the research will eventually help with early diagnosis and intervention for depression and other psychiatric illnesses, and could help lead the way toward developing more individualized therapies.

“We’ve identified a biomarker - in this case genetic variation - that is linked with increased risk of major depression,” said the study’s senior author Jon-Kar Zubieta, a professor of psychiatry and radiology and research professor at the Molecular and Behavioral Neurosciences Institute.

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

The study found that people who produce lower amounts of NPY had measurably stronger brain responses to negative stimuli and psychological responses to physical pain.

They were also over-represented in a population diagnosed with a major depressive disorder.

The researchers used three different approaches, each with a varying number of research subjects ranging from 58 to 152, to study the link between NPY gene expression and emotional processing.

First, they classified subject participants into three categories according to low, medium or high NPY expression.

Using functional magnetic resonance imaging (fMRI), they then observed the brain activity as the subjects viewed different words - some neutral (such as ‘material’) negative (like ‘murderer’), and positive words (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.

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.

Finally, the researchers compared the NPY genotypes of subjects with major depressive disorders with control subjects and found that people with low NPY were ‘over-represented’ in the group with depression.

“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,” said lead author Brian Mickey, an assistant professor in the Department of Psychiatry at the University of Michigan Medical School.

The findings are published in the Archives of General Psychiatry. (ANI)

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