Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene influences antidepressant response

17.03.2006


Whether depressed patients will respond to an antidepressant depends, in part, on which version of a gene they inherit, a study led by scientists at the National Institutes of Health (NIH) has discovered. Having two copies of one version of a gene that codes for a component of the brain’s mood-regulating system increased the odds of a favorable response to an antidepressant by up to 18 percent, compared to having two copies of the other, more common version.



Since the less common version was over 6 times more prevalent in white than in black patients – and fewer blacks responded – the researchers suggest that the gene may help to explain racial differences in the outcome of antidepressant treatment. The findings also add to evidence that the component, a receptor for the chemical messenger serotonin, plays a pivotal role in the mechanism of antidepressant action. The study, authored by National Institute of Mental Health (NIMH) researchers Francis J. McMahon, M.D., Silvia Buervenich, Ph.D., and Husseini Manji, M.D., along with collaborators at the National Human Genome Research Institute (NHGRI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and other institutions, was posted online March 8 and will appear in the May, 2006 American Journal of Human Genetics.

"This discovery brings us closer to the day when clinicians will be able to offer treatment options and medications that are tailored and personalized to be optimally effective for individual patients," said NIH Director Elias A. Zerhouni, M.D.


However, the findings cannot yet guide treatment decisions.

"To our knowledge, this is the first demonstration of significant, replicated association between genetic variation and outcome of antidepressant treatment," added Manji, director of the NIMH’s Mood and Anxiety Disorders Program.

In the initial phase of the NIMH-funded STAR*D (Sequenced Treatment Alternatives for Depression) trial, about 47 percent of the 2,876 participants experienced some improvement with the serotonin selective reuptake inhibitor (SSRI) citalopram (Celexa). The NIH scientists set out to find genetic factors that might help to explain why some patients fared better than others.

They screened genetic material from 1,953 of the STAR*D patients, a sample with a higher percentage of responders (69 percent), in part because patients who were doing well tended to stay in contact longer and were more likely to allow a blood sample to be drawn. The researchers looked for associations between treatment response and 768 known sites of variability in 68 suspect genes – sites where letters in the genetic code vary across individuals.

They found the strongest connection in the gene that codes for the serotonin 2A receptor, one of several proteins to which serotonin binds when brain cells communicate.

Located on cells in the brain’s thinking center (cortex), the serotonin 2A receptor regulates circuits implicated in depression. Antidepressants, including citalopram, reduce the number of serotonin 2A receptors in animal cortex over the course of a few weeks – the same time-frame required for the drugs to work in humans – suggesting that the receptors are important in the drugs’ mechanism of action.

Everyone inherits two copies of the serotonin 2A receptor gene, one from each parent. A tiny glitch in the gene’s chemical sequence results in some people having an adenine (A) at the same point that other people have a guanine (G). So an individual can have gene types AA, AG or GG. Overall, the prevalence of the A version was 38 percent, compared to 62 percent for the G version in this sample. Fourteen percent had AA gene type, 43 percent AG and 43 percent GG. Since the site of variation is located in a stretch of genetic material with no known function, the researchers suspect that it may be just a marker for a still-undiscovered functional variation nearby in the gene.

Based on scores on a depression rating scale, close to 80 percent of patients who had AA responded to the antidepressant, compared to about 62 percent of those with GG. Thus, patients with the AA gene type were 16-18 percent more likely to benefit from the medication. Even patients with AG showed some increased benefit.

But this only applied to white patients, in whom the A version was more than six times more frequent than in black patients. There was no significant association between gene type and treatment outcome in black patients, who tended to fare less well in the trial overall.

"We now have to consider genetic factors as well as psychosocial issues in our attempts to explain why antidepressants do not help our black patients as much as they should," McMahon said. "The new findings help make a compelling case for a key role of the serotonin 2A receptor in the mechanism of antidepressant action."

Also participating in the study were: A. John Rush and Madhukar Trivedi, University of Texas Southwestern Medical Center; Gonzalo Laje, NIMH; Dennis Charney, Mount Sinai Hospital; Robert Lipsky, National Institute on Alcohol Abuse and Alcoholism (NIAAA); Alexander Wilson, Alexa Sorant, and George Papanicolaou, National Human Genome Research Institute (NHGRI); Maurizio Fava, Massachusetts General Hospital; and Stephen Wisniewski, University of Pittsburgh.

Jules Asher | EurekAlert!
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Lightning, with a chance of antimatter

24.11.2017 | Earth Sciences

A huge hydrogen generator at the Earth's core-mantle boundary

24.11.2017 | Earth Sciences

Scientists find why CP El Niño is harder to predict than EP El Niño

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>