UIC Researchers May Have Found Test for Depression
[Writer] This is Research News from U-I-C, the University of Illinois at Chicago.
Today, Mark Rasenick, distinguished university professor in biophysics, and physiology and psychiatry talks about his lab’s new discovery. A change in the location of a protein in the brain could serve as a biomarker for depression. That could make it possible for a simple rapid laboratory test to identify patients with depression and determine whether a chosen antidepressant therapy will provide a successful response.
Here is Professor Rasenick:
[Rasenick] We’ve been working for several years on the possibility that a molecule called a G protein that mediates the actions of neurotransmitters such as serotonin is restricted to lipid rafts under conditions where it becomes inactivated. When it becomes activated by the receptor, some of it stays in these lipid rafts and is lost to the world by being internalized in the cell and some of it moves out of the rafts and becomes more tightly associated with the enzyme called adenylyl cyclase that’s going to make it work inside the cell. We’ve followed this for many years. We understand how the process works now. We understand the molecules that are involved in setting up the process.
At the same time, we’ve been very interested in the molecular basis of antidepressant action and our first paper on that, as a matter of fact, was in 1983 and we’ve gone back and forth on that. There is a human aspect to this. One of my sons is depressed and I became more and more interested in trying to figure out what it was that’s involved. What’s the biochemistry of depression? And unfortunately, that’s remained elusive. There are some genes that may be involved but they don’t explain the story.
And one of the other very confusing aspects of antidepressants is that antidepressant therapy requires about a month to work. Now, if you look simply at a gene, a gene gets turned on or off in minutes. If you look at what is commonly thought to be an action of antidepressants—that is many of them block the uptake of neurotransmitters—that happens in seconds to minutes. So what’s going on? Why is this taking a month? And we have looked at this from a molecular level in both cultured human cells and in rats, and we had seen that the G protein that we’re interested in seem to move out of these lipid rafts and it worked better after chronic treatment with antidepressants. Now when I say chronic treatment, in rats, just like humans, it took about a month to work, but in the cells it was about four or five days. So that gave us the idea that perhaps antidepressants could have an effect on cells, like peripheral cells or just blood cells, much more quickly than they would in the brain. And we were able to see a change very quickly in peripheral tissues like blood cell, where is in the brain or in behavior it would take about a month to have an effect.
With this as a background, we began to work with our colleague, Subhash Pandey here at UIC and Subhash has always been interested in postmortem studies. And he has access to a series of brains in Baltimore where at least 16 of these people are suicide victims with a complete psychiatric history. So these were people that, not only were they suicides, but they were documented as being depressed. And we had sixteen controls that were documented as having no psychiatric history. And when we looked at that, low and behold, and went back to thinking about our G proteins, remember that the antidepressants made the G protein go out of the lipid raft and work better, and the G protein was twice as likely to be in a lipid raft in the depressed humans. So it said to us, ’Gee this is really something,’ because now we’ve looked at humans with documented depression and it verifies all the in vitro work that we’ve done, and it also the presages idea that we might be able to develop a blood test for depression. And what’s even more interesting is that the test that could be developed based on this is a very simple one that could be done in a clinical laboratory. It’s not one that requires a gene array or a complex series of interactions that would need to be done in a sophisticated lab. This is very unsophisticated. But it looks like it might be right and we’re very excited with the possibility that in four or five days we’d be able to determine whether an individual were getting the appropriate therapy and if not, we could switch therapy. For all we know, this would even work for psychotherapy. That has to be born out because clearly, even in the case of psychotherapy, it’s all biology. That’s one of the things we need to stress, that depression and other psychiatric illnesses are all biology. If you’re going through analysis, there’s a biological effect to it. That’s what we want to get and we think that by doing that we also help to erase some of the stigma of mental illness. That’s very important. Now what we need to do is get the appropriate funds to do what we want to do and as you know, that’s been a problem lately for some many people doing science.
[Writer] Mark Rasenick is a distinguished university professor in physiology, biophysics and psychiatry.
For more information about this research, go to www-dot-news-dot- uic-dot-edu … click on “news releases” … and look for the release dated March 11, 2008.
This has been research news from U-I-C – the University of Illinois at Chicago.