Sometimes more is not always better.
Researchers recently discovered a protein that is more prominent in the brains of people suffering from depression.
The study, led by University of Michigan neuroscience doctoral student Elyse Aurbach, discovered the protein fibroblast growth factor 9 — or FGF9 — was enhanced in depressed people.
In people with major depression the study found 32 percent more FGF9 in a key part of the brain than those without depression.
In addition, the researchers added FGF9 to rats and it led to depression-like behavioral changes.
Aurbach and her team concluded that depression is a physical illness.
“Many people in many labs have found connections between genetics, neurobiology, and depression, so our work is part of a much larger whole,” Aurbach told Healthline. “For the last few years, our lab and the Pritzker Consortium have been trying to understand how the activity of genes in the brain are altered in people who suffered from depression during life by looking at changes in many genes across many parts of the brain.”
Possible New Drug Strategies
The researchers said the discovery could lead to antidepressant drugs that would block excess production of FGF9. Drugs that block excess production typically have fewer side effects than those that increase a substance.
Working with her mentor Huda Akil, Ph.D., co-director and research professor of the Molecular & Behavioral Neuroscience Institute, as well as professor of neuroscience at the University of Michigan, Aurbach and her team honed in on the fibroblast growth factors, which are molecules involved in cell growth as well as maintenance in the brain and other areas of the body.
The study, according to Aurbach, would not have been able to find everything it did if not for working at Akil’s lab, where the focus is on several angles of mood disorders.
“I want to understand the biological basis of mood disorders because I am close to people who suffer from depression,” Aurbach said. “Dr. Akil's lab was therefore a natural fit for me when I started graduate school because we study mood disorders from a number of angles, including by examining the donated brains of people who suffered from depression during life and by studying models of depression in rodents.”
“Scientifically, this is a very powerful combination,” she added, “because many labs are able to study these questions from one angle or the other but not both.”
One Protein Lower, Another Higher
After finding that another molecule, FGF2, was lower in people and animals with depression in an earlier portion of the study, the team was somewhat surprised at the reverse situation with FGF9.
The findings were discovered postmortem with the help of the brain bank at the University of California, Irvine, supported by the Pritzker Consortium.
Several experiments showed higher FGF9 levels in depressed brains. Compounding those findings, the team discovered other FGF molecules were lower when FGF9 was raised.
“We're discovering that depressed individuals can simultaneously have too little of some chemicals, like serotonin, and too much of others, like FGF9,” Aurbach said. “By identifying genes like FGF9 that are too high in depressed brains, we have the opportunity to determine if blocking their activity helps with the symptoms of depression.”
“So while lots of work needs to be done before we can use our findings to develop a new drug,” she continued, “we're learning that FGF9 may be a good target for a new kind of antidepressant.”
The team wanted to look more into the role of FGF9 by experimenting on rats, with the hope to determine if FGF9 rises in response to anything.
The team has filed a patent application they hope will lead their work to a medication for FGF9 levels.
“We're working on many studies to better understand FGF9. We're interested in how FGF9 levels change in depression for many brain regions and we're trying to understand if and how FGF9 interacts with other genes to have effects on mood,” Aurbach said. “In particular, we're very interested in how FGF9 interacts with another member of its molecular family, FGF2, because it seems that FGF2 and FGF9 are acting in the brain to produce opposite effects on depression and behavior.”
Aurbach insists the studies now will be more influential to antidepressants than ever before.
“Current treatments like therapy and antidepressant drugs aren't effective for almost one in three people with depression,” she said. “Our work is particularly relevant for these depressed people and their families because a better understanding of the underlying neurobiology in depression will allow scientists to develop different kinds of treatments, which may be more effective than those we have now.”