March 11, 2008 / 10:33 PM / 12 years ago

Protein discovery could lead to depression test

CHICAGO (Reuters) - Changes in the location of a single protein in the brain could be used to tell whether a person with depression is responding to an antidepressant within days of taking the drug, U.S. researchers said on Tuesday.

People with depression now must wait weeks before they learn whether the drug they are taking will bring relief.

But researchers at the University of Illinois at Chicago have discovered that a single protein in the brain changes its location within a cell membrane when an antidepressant is working, and this change could be identified with a simple blood test.

“The possibility there, is if we look at blood from a patient on day zero and day four or five, we’ll know whether the antidepressant would be effective,” said UIC’s Dr. Mark Rasenick, whose study appears in the Journal of Neuroscience.

His team compared brain samples from depressed people who had committed suicide with those from people who had no history of psychiatric disorders.

What they found was a key difference in the location of a signaling protein known as Gs alpha — which is important for the action of neurotransmitters or message-carrying chemicals such as serotonin.

In people with depression, this protein is trapped in what Rasenick called a “lipid raft” inside the cell membrane. While stuck in this thick, gluey area of the cell, the signaling protein seemed less effective at directing the action of message-carrying chemicals.

In tests on rats and in cell cultures done in Rasenick’s lab, antidepressants helped move the Gs alpha protein into an area of the cell where it could be more effective.

“The antidepressant causes this protein to move out of a little prison in the cell membrane called a lipid raft so that it works better. That was all established by very basic studies on rats or cells,” Rasenick said in a telephone interview.

“What this study demonstrated in depressed suicides is that in depression, you had exactly the opposite effect. This G protein was more than twice as likely to be imprisoned in those lipid rafts. And then it didn’t work as well,” he said.

He said the method worked with selective serotonin reuptake inhibitors, or SSRIs, such as Prozac, as well as the older tricyclic antidepressants.

Rasenick said using this protein as a biomarker, a simple blood test could be made that would confirm a depression diagnosis or determine whether an antidepressant is working.

It also gives a clearer picture of the chemical changes in the brain underlying depression.

“The notion here is that depression is really a biological illness. So many people refuse to seek medical help for this. They talk to their bartender but they don’t talk to their doctor. Studies like this help to reinforce not only that this is a medical problem, but that there is a clear chemical change,” he said.

Editing by Maggie Fox and Philip Barbara

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