Featured Research

from universities, journals, and other organizations

Surplus of serotonin receptors may explain failure of antidepressants in some patients

Date:
January 14, 2010
Source:
Columbia University Medical Center
Summary:
An excess of one type of serotonin receptor in the center of the brain may explain why antidepressants fail to relieve symptoms of depression for 50 percent of patients, a new study shows. The study is the first to find a causal link between receptor number and antidepressant treatment and may lead to more personalized treatment.

An excess of one type of serotonin receptor in the center of the brain may explain why antidepressants fail to relieve symptoms of depression for 50 percent of patients, a new study from researchers at Columbia University Medical Center shows.

The study is the first to find a causal link between receptor number and antidepressant treatment and may lead to more personalized treatment for depression, including treatments for patients who do not respond to antidepressants and ways to identify these patients before they undergo costly, and ultimately, futile therapies.

The research, led by Rene Hen, PhD, professor of pharmacology in the Departments of Psychiatry and Neuroscience at Columbia University, and a researcher the New York State Psychiatric Institute, appears in the January 15 issue of the journal Neuron.

Most antidepressants -- including the popular SSRIs -- work by increasing the amount of serotonin made by cells -- called raphe neurons -- deep in the middle of the brain. Serotonin relieves symptoms of depression when it is shipped to other brain regions.

But too many serotonin receptors of the 1A type on the raphe neurons sets up a negative feedback loop that reduces the production of serotonin, Dr. Hen and his colleagues discovered

"The more antidepressants try to increase serotonin production, the less serotonin the neurons actually produce, and behavior in mice does not change," Dr. Hen says.

Dr. Hen and his colleagues measured the effect of antidepressants with a commonly used behavioral test that measures the boldness in mice when retrieving food from bright open areas. Mice on antidepressants usually become more daring, but the drugs had no such effect on mice with surplus serotonin receptors.

Recent genetic and imaging studies of depressed patients have suggested that high receptor numbers of the 1A type in the raphe neurons are associated with treatment failure. Until now, no direct test of the association could be performed because the number of receptors in the raphe neurons could not be altered without changing the number of receptors in other parts of the brain.

Using new techniques in genetic engineering, Dr. Hen created a strain of mouse that can be programmed to produce high or low levels of serotonin receptors of the 1A type only in the raphe neuron. The levels present in the mice mimicked the levels found in people who are resistant to antidepressant treatment.

"By simply tweaking the number of receptors down, we were able to transform a non-responder into a responder," Dr. Hen adds.

That strategy also may work for patients resistant to antidepressant treatment, Dr. Hen says, if drugs can be found to reduce the number of receptors or impede their activity.

But first the role of surplus serotonin receptors in people must be confirmed. Dr. Hen's lab is now looking at patients enrolled in clinical trials to see if receptor levels predict response to antidepressants.

Authors of the Neuron study are Jesse W. Richardson-Jones, Caryne P. Craige, Bruno P. Guiard, Alisson Stephen, Kayla L. Metzger, Hank F. Kung, Alain M. Gardier, Alex Dranovsky, Denis J. David, Sheryl G. Beck, Rene Hen and E. David Leonardo.

This study was supported in part by NIMH, NARSAD and AstraZeneca.


Story Source:

The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Columbia University Medical Center. "Surplus of serotonin receptors may explain failure of antidepressants in some patients." ScienceDaily. ScienceDaily, 14 January 2010. <www.sciencedaily.com/releases/2010/01/100113122303.htm>.
Columbia University Medical Center. (2010, January 14). Surplus of serotonin receptors may explain failure of antidepressants in some patients. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2010/01/100113122303.htm
Columbia University Medical Center. "Surplus of serotonin receptors may explain failure of antidepressants in some patients." ScienceDaily. www.sciencedaily.com/releases/2010/01/100113122303.htm (accessed October 2, 2014).

Share This



More Mind & Brain News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Stopping School Violence

Stopping School Violence

Ivanhoe (Oct. 1, 2014) A trauma doctor steps out of the hospital and into the classroom to teach kids how to calmly solve conflicts, avoiding a trip to the ER. Video provided by Ivanhoe
Powered by NewsLook.com
Pineal Cysts: Debilitating Pain

Pineal Cysts: Debilitating Pain

Ivanhoe (Oct. 1, 2014) A tiny cyst in the brain that can cause debilitating symptoms like chronic headaches and insomnia, and the doctor who performs the delicate surgery to remove them. Video provided by Ivanhoe
Powered by NewsLook.com
Burning Away Brain Tumors

Burning Away Brain Tumors

Ivanhoe (Oct. 1, 2014) Doctors are 'cooking' brain tumors. Hear how this new laser-heat procedure cuts down on recovery time. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins