Neuroscientists put heads together to develop new theory on depression
Steven Schultz
Depression, an illness that affects about 10 million Americans a year, may be caused by a lack of nerve cell generation in the brain, according to Princeton neuroscientist Barry Jacobs.
|
|
|
|
Barry Jacobs
|
|
Jacobs theorizes that not only does the brain generate new neurons, but this constant influx is critical in maintaining psychological well-being. In short, he suggests that a decreased flow of new neurons plays an important role in precipitating depression and that an increased flow helps bring about recovery. This process, says Jacobs, occurs primarily in a brain region called the hippo-campus, which is involved with learning and memory, but probably in other brain areas as well. If proven in humans, the theory could open new avenues for treating depression.
"This (theory) brings together two very interesting and important lines of work in neuroscience," said Bruce McEwen, a neuroscientist at Rockefeller University.
Jacobs, a professor of psychology, is an expert on serotonin, a brain chemical closely tied to depression. Antidepressant drugs work by boosting or mimicking the activity of serotonin. It is not clear, however, what serotonin does to counteract depression.
Gould, also a professor of psychology, has focused her research on the birth of new neurons a process called neurogenesis. In a series of landmark papers, she showed that neurogenesis is a life-long process, refuting the long-held belief that the adult brain never gains neurons and only loses them.
In what Jacobs describes as "a remarkable example of cross-fertilization among colleagues," he and Gould began to see possible links between their research agendas, and wondered whether serotonin promotes neurogenesis. They conducted tests in rats and showed that it does. In one experiment, Jacobs and collaborators administered the antidepressant drug Prozac to rats for three weeks and found a 70 percent increase in neurogenesis in the hippocampus.
"As soon as we showed that serotonin was important in neurogenesis, it occurred to me that neurogenesis might be important in recovery from depression," he said.
Jacobs further developed the idea when he spent a sabbatical working with neuroscientist Fred Gage of the Salk Institute in San Diego. Gage, who is his co-author on the papers that describe the new theory of depression, has shown that exercise and a stimulating environment both factors that might relate to depression promote neurogenesis in rats.
As Jacobs originally discussed in the May issue of Molecular Psychiatry, several other lines of reasoning support his hypothesis. Recent research by Gould has shown, for example, that stress, which is a common trigger for depression, also is a potent suppressor of neurogenesis. Stress promotes the release of steroids, which inhibit new cell development in the hippocampus.
Using MRI scans, other researchers had also shown that the size of the hippocampus is reduced in patients with depression. Also, patients who suffer from a form of epilepsy that severely impairs the hippocampus have a high incidence of depression.
Although the theory fits well with these human and animal studies, said Jacobs, "The real issue now is: Does this really happen in people?"
The true test, he said, would be to observe directly the birth of new neurons in people with depression and to compare the observations to those of healthy people. Unfortun-ately, such technology does not exist, although Jacobs expressed confidence that it will be developed. In the meantime, there are further animal tests that could give the theory additional backing. One such test would be to suppress neurogenesis in animals and look for signs of depression, and then to treat the animals with neurogenesis-inducing drugs and look for signs of recovery. Jacobs is seeking funding from pharmaceutical developers to conduct such work.
If the theory can be proven in humans, it could suggest two new strategies for treating depression, Jacobs said. Doctors may one day be able to harvest immature cells, called stem cells, from the brain, grow them into adult neurons in the lab and then return them to the hippocampus. Or, a less invasive strategy would be to develop a drug that works specifically to induce the production of new neurons in the appropriate brain region.
Jacobs is eager to pin down the next experiments that will add further support to the theory. "I'm excited about it and I've gotten a lot of good reactions to it thus far," he said.
|
[an error occurred while processing this directive] |