Featured Research

from universities, journals, and other organizations

Genome Wide Search For Genes Underlying Anxiety Disorders Turns Up Unexpected Candidates

Date:
October 30, 2005
Source:
Salk Institute
Summary:
Increasing the activity of two enzymes better known for their role in oxidative stress metabolism turns normally relaxed mice into "Nervous Nellies," according to research conducted at the Salk Institute for Biological Studies and reported in the early online edition of Nature.

Increasing the activity of two enzymes better known for their role in oxidative stress metabolism turns normally relaxed mice into "Nervous Nellies," according to research conducted at the Salk Institute for Biological Studies and reported in the early online edition of Nature.

Related Articles


Locally overexpressing either glyoxalase 1 or glutathione reductase 1 in mouse brains significantly increased anxiety in usually relaxed mice and made already jittery mice even more anxiety-ridden. Inhibition of glyoxalase 1 had the opposite effect.

"Currently, very little is known about the genes that predispose to psychiatric disease," says first author Iiris Hovatta, who was a postdoctoral research in Salk's Laboratory of Genetics when the research was conducted. "All of the 17 genes that we identified are very good candidates for human anxiety disorders and most of them have never been associated with anxiety-related behavior before," she adds.

"This is a very exciting study where we can genetically interfere with the behavior outcome, emphasizing the genetic hard wiring of certain traits,'' says Inder Verma, professor in the Laboratory for Genetics at the Salk Institute.

Out of the 17 candidates, the researchers focused on the most promising ones, glyoxalase 1 and glutathione reductase 1, since both enzymes belonged to the same metabolic pathway. In addition, a study by Turkish scientists had found elevated levels of oxidative stress markers in patients with severe anxiety disorders. "It might be that oxidative stress metabolism and anxiety levels are linked, although we do not know the exact mechanism at the moment," says Hovatta.

Like other complex psychiatric traits, fear and anxiety are influenced by many genes. There is no such thing as a single "fear" gene that lets anxiety spiral out of control when the gene's regulation is disturbed, making it difficult to identify the genetic roots of anxiety disorders.

For their study, the scientists relied on inbred mouse strains that differ considerably in their natural anxiety levels. Just like in humans suffering from anxiety disorders, the sights and sounds of unfamiliar environments can trigger panic in mice with anxious dispositions, causing them to freeze in place. Unlike their more relaxed contemporaries, naturally nervous mice are not explorers and may seem wary of open spaces.

Instead of studying individual genes the researchers simultaneously assessed the activity patterns of about 10,000 genes in specific brain regions with the help of microarrays. This extensive scan allowed the researchers to pinpoint multiple genes whose expression levels differed in relaxed and anxiety-prone mice.

To increase the specificity of their microarray analysis, they looked in only specific brain areas that have been shown to play a role in anxiety and fear (the amygdala, bed nucleus of the stria terminalis, cingulate cortex, hippocampus, hypothalamus, central peri-aqueductal grey and pituitary gland).

"We were incredibly surprised since out of the entire genome only 17 genes were robustly correlated with anxiety levels across many different strains," says Carrolee Barlow, lead author of the study and an adjunct professor in the Laboratory of Genetics. "Almost half of them were enzymes and not neurotransmitters as one might expect."

In the past, scientists tried to correlate complex psychiatric diseases with different forms of the genes controlling neurotransmitters, the chemical messengers that brain cells use to shuttle outgoing signals to neighboring cells, and their receptors, albeit with limited success. "That's why we chose an unbiased approach that didn't limit us to neurotransmitters," explains Barlow.

Now, Hovatta wants to find out what relevance, if any, the identified genes have to human anxiety disorders. "It is really exciting to study neurobiology of anxiety in mice and to understand the molecular mechanisms behind the regulation of behavior, but I am mostly interested in trying to find genes that predispose humans to anxiety disorders and to perhaps in the future try to develop better treatment practices. We are still far away from that," she cautions, "but it is the long term goal of the project."

Researchers contributing to the study include first author Iiris Hovatta, formerly at the Salk Institute, now at National Public Health Institute in Helsinki Finland, research assistants Richard S. Tennant and Robert Helton, research fellows Robert A. Marr and Oded Singer, both in the Laboratory of Genetics at the Salk Institute, Jeffrey M. Redwine at Neurome Inc., Julie A. Ellison, formerly at the Salk, now at Helix Medical Communications, Eric E. Schadt at Rosetta Inpharmatics LLC, Inder Verma, professor in the Laboratory for Genetics at the Salk Institute, David J. Lockhart, co-principal investigator and visiting scholar at the Salk Institute, and Carrolee Barlow, at Braincells Inc.

###

About Salk Institute for Biological Studies:
Internationally renown for its groundbreaking basic research in the biological sciences, the Salk Institute was founded in 1960 by Dr. Jonas Salk, just five years after he developed the first safe, effective vaccine against polio. The institute's 57-member faculty are scientific leaders in the fields of molecular biology, neurosciences and plant biology.


Story Source:

The above story is based on materials provided by Salk Institute. Note: Materials may be edited for content and length.


Cite This Page:

Salk Institute. "Genome Wide Search For Genes Underlying Anxiety Disorders Turns Up Unexpected Candidates." ScienceDaily. ScienceDaily, 30 October 2005. <www.sciencedaily.com/releases/2005/10/051029093735.htm>.
Salk Institute. (2005, October 30). Genome Wide Search For Genes Underlying Anxiety Disorders Turns Up Unexpected Candidates. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2005/10/051029093735.htm
Salk Institute. "Genome Wide Search For Genes Underlying Anxiety Disorders Turns Up Unexpected Candidates." ScienceDaily. www.sciencedaily.com/releases/2005/10/051029093735.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
Yoga Could Be As Beneficial For The Heart As Walking, Biking

Yoga Could Be As Beneficial For The Heart As Walking, Biking

Newsy (Dec. 17, 2014) Yoga can help your weight, blood pressure, cholesterol and heart just as much as biking and walking does, a new study suggests. Video provided by Newsy
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