Featured Research

from universities, journals, and other organizations

Mutant Gene Linked To Treatment-Resistant Depression

Date:
December 17, 2004
Source:
NIH/National Institute Of Mental Health
Summary:
A mutant gene that starves the brain of serotonin, a mood-regulating chemical messenger, has been discovered and found to be 10 times more prevalent in depressed patients than in control subjects, report researchers funded by the National Institutes of Health's National Institute of Mental Health (NIMH) and National Heart Lung and Blood Institute (NHLBI).

A mutant gene that starves the brain of serotonin, a mood-regulating chemical messenger, has been discovered and found to be 10 times more prevalent in depressed patients than in control subjects, report researchers funded by the National Institutes of Health's National Institute of Mental Health (NIMH) and National Heart Lung and Blood Institute (NHLBI). Patients with the mutation failed to respond well to the most commonly prescribed class of antidepressant medications, which work via serotonin, suggesting that the mutation may underlie a treatment-resistant subtype of the illness.

The mutant gene codes for the brain enzyme, tryptophan hydroxylase-2, that makes serotonin, and results in 80 percent less of the neurotransmitter. It was carried by nine of 87 depressed patients, three of 219 healthy controls and none of 60 bipolar disorder patients. Drs. Marc Caron, Xiaodong Zhang and colleagues at Duke University announced their findings in the January 2005 Neuron, published online in mid-December.

"If confirmed, this discovery could lead to a genetic test for vulnerability to depression and a way to predict which patients might respond best to serotonin-selective antidepressants," noted NIMH Director Thomas Insel, M.D.

The Duke researchers had previously reported in the July 9, 2004 Science that some mice have a tiny, one-letter variation in the sequence of their tryptophan hydroxylase gene (Tph2) that results in 50-70 percent less serotonin. This suggested that such a variant gene might also exist in humans and might be involved in mood and anxiety disorders, which often respond to serotonin selective reuptake inhibitors (SSRIs) — antidepressants that block the re-absorption of serotonin, enhancing its availability to neurons.

In the current study, a similar variant culled from human subjects produced 80 percent less serotonin in cell cultures than the common version of the enzyme. More than 10 percent of the 87 patients with unipolar major depression carried the mutation, compared to only one percent of the 219 controls. Among the nine SSRI-resistant patient carriers, seven had a family history of mental illness or substance abuse, six had been suicidal and four had generalized anxiety.

Although they fell short of meeting criteria for major depression, the three control group carriers also had family histories of psychiatric problems and experienced mild depression and anxiety symptoms. This points up the complexity of these disorders, say the researchers. For example, major depression is thought to be 40-70 percent heritable, but likely involves an interaction of several genes with environmental events. Previous studies have linked depression with the same region of chromosome 12, where the tryptophan hydroxylase-2 gene is located. Whether the absence of the mutation among 60 patients with bipolar disorder proves to be evidence of a different underlying biology remains to be investigated in future studies.

The researchers say their finding "provides a potential molecular mechanism for aberrant serotonin function in neuropsychiatric disorders."

Also participating in the study were: Raul Gainetdinov, Jean-Marin Beaulieu, Tatyana Sotnikova, Lauranell Burch, Redford Williams, David Schwartz, and Ranga Krishnan, Duke University.

In addition to grants from NIMH and NHLBI, the study was also funded by the Human Frontiers Science Program and the Canadian Institute of Health Research.

NIMH and NHLBI are part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services.

To learn more, visit the following links:

Depression: http://www.nimh.nih.gov/HealthInformation/Depressionmenu.cfm

Bipolar Disorder: http://www.nimh.nih.gov/healthinformation/bipolarmenu.cfm

PubMed abstract of July 9, 2004 Science article:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15247473


Story Source:

The above story is based on materials provided by NIH/National Institute Of Mental Health. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Mental Health. "Mutant Gene Linked To Treatment-Resistant Depression." ScienceDaily. ScienceDaily, 17 December 2004. <www.sciencedaily.com/releases/2004/12/041217102737.htm>.
NIH/National Institute Of Mental Health. (2004, December 17). Mutant Gene Linked To Treatment-Resistant Depression. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2004/12/041217102737.htm
NIH/National Institute Of Mental Health. "Mutant Gene Linked To Treatment-Resistant Depression." ScienceDaily. www.sciencedaily.com/releases/2004/12/041217102737.htm (accessed August 23, 2014).

Share This




More Mind & Brain News

Saturday, August 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Charter Schools Alter Post-Katrina Landscape

Charter Schools Alter Post-Katrina Landscape

AP (Aug. 20, 2014) Nine years after Hurricane Katrina, charter schools are the new reality of public education in New Orleans. The state of Louisiana took over most of the city's public schools after the killer storm in 2005. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
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:
from the past week

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