New Studies Examine the Many Facets of Depression
Treatments for depression have improved greatly over the years, yet there are still many patients not helped by traditional offerings of medications and talk therapy.
”Roughly 20 to 40 percent of people with depression aren’t helped by existing therapies,” said Robert Greene, M.D., Ph.D., of the University of Texas Southwestern Medical School in Dallas. On Monday, he moderated a news conference at the annual meeting of the Society of Neuroscience in San Diego to update research on new options under study.
Among the promising research is new data on:
- How being stressed out may play a role in depression;
- How the immune system may play a role in depression;
- The role of a specific molecule, Cdk5, in nerve cell signaling and how the information might be used for an antidepressant effect;
- The role of a small protein known as p11 and how it affects antidepressant-like responses.
To the first of these, Herwig Baier, Ph.D., a researcher at the University of California San Francisco, said, ”An inability to cope with stress may play a role in depression.” He found in a study that zebra fish who have a mutation in a receptor important for stress management displayed abnormal behavior similar to depression. Normally social fish, the zebra fish stopped swimming and hid in the corner of their tanks when isolated from others.
But when these fish were given fluoxetine (Prozac), the behavior disappeared, he found. Studying the fish makes sense, Baier says, as the ”stress axis” in this fish and humans is identical.
The zebra fish’s mutation is in the gene known as the glucocorticoid receptor (GR) gene, and one of its jobs is to ”dial down” the secretion of stress hormones from the brain. Either too much or too little GR activity has been linked with depression.
If the fish story holds true for people, Baier said, new strategies for depression could be developed that don’t block GR activity but activate it to just the right amount so mood is not depressed.
The immune system could also play a role in depression, said Simon Sydserff, PHD, a senior research scientist at BrainCells, Inc., a drug development company in San Diego involved in stem cell technology to develop CNS treatments.
Here’s how: When you get sick, the immune system hormone IL6 or interleukin 6, carries ”sickness” signals to the brain. When Sydserff activated the immune system of mice to mimic sickness, they displayed behavior representing depression.
“Patients who are depressed who are medically healthy and also those who are medically ill, have high levels of immune system signaling cytokines such as IL6,” he said.
“Interferon alpha, a cancer treatment, increases IL-6 and has also been linked to major depression,” he said. If the research bears out, he said, ”blocking IL-6 may prevent or reverse depression,” offering another option.
He conducted the research, supported by AstraZeneca Pharmaceuticals, while on staff there.
In another study, James Bibb, Ph.D., of the University of Texas Southwestern Medical Center, Dallas, found that mice lacking a molecule known as Cdk5 like mice given an antidepressant: They were more active, one marker of effective antidepressant action. Without the molecule, the wave of a signaling molecule known as cyclic AMP doesn’t stop as it typically does, and this was linked with antidepressant-like responses. Learning how to block this molecule in the future could provide more options, he said.
Meanwhile, figuring out why an antidepressant can take a while to ”kick in” is the focus of another study. Jennifer Warner-Schmidt, Ph.D., a researcher at The Rockefeller University in New York, zeroed in on a regulator of antidepressant responses known as p11. It’s a small protein expressed in depression-related brain regions.
She found in animal studies that over-expression of p11 results in an antidepressant effect and that another key regulator, brain-derived neurotrophic factor (BDNF) is required for the serotonin-induced increase in the p11.
”Understanding better the role of p11 in antidepressant response could lead to faster acting antidepressants with fewer side effects,” she said.
SOURCE: Society for Neuroscience.
Doheny, K. (2015). New Studies Examine the Many Facets of Depression. Psych Central. Retrieved on October 4, 2015, from http://psychcentral.com/news/2010/11/18/new-studies-examine-the-many-facets-of-depression/20997.html