Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

A Personal Antidepressant for Every Genome

Published: Wednesday, December 18, 2013
Last Updated: Wednesday, December 18, 2013
Bookmark and Share
TAU researchers discover gene that may predict human responses to specific antidepressants.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants, but they don't work for everyone. What's more, patients must often try several different SSRI medications, each with a different set of side effects, before finding one that is effective. It takes three to four weeks to see if a particular antidepressant drug works. Meanwhile, patients and their families continue to suffer.

Now researchers at Tel Aviv University have discovered a gene that may reveal whether people are likely to respond well to SSRI antidepressants, both generally and in specific formulations. The new biomarker, once it is validated in clinical trials, could be used to create a genetic test, allowing doctors to provide personalized treatment for depression.

Doctoral students Keren Oved and Ayelet Morag led the research under the guidance of Dr. David Gurwitz of the Department of Molecular Genetics and Biochemistry at TAU's Sackler Faculty of Medicine and Dr. Noam Shomron of the Department of Cell and Developmental Biology at TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience. Sackler faculty members Prof. Moshe Rehavi of the Department of Physiology and Pharmacology and Dr. Metsada Pasmnik-Chor of the Bioinformatics Unit were coauthors of the study, published in Translational Psychology.

"SSRIs only work for about 60 percent of people with depression," said Dr. Gurwitz. "A drug from other families of antidepressants could be effective for some of the others. We are working to move the treatment of depression from a trial-and-error approach to a best-fit, personalized regimen."

Good news for the depressed

More than 20 million Americans each year suffer from disabling depression that requires clinical intervention. SSRIs such as Prozac, Zoloft, and Celexa are the newest and the most popular medications for treatment. They are thought to work by blocking the reabsorption of the neurotransmitter serotonin in the brain, leaving more of it available to help brain cells send and receive chemical signals, thereby boosting mood. It is not currently known why some people respond to SSRIs better than others.

To find genes that may be behind the brain's responsiveness to SSRIs, the TAU researchers first applied the SSRI Paroxetine — brand name Paxil — to 80 sets of cells, or "cell lines," from the National Laboratory for the Genetics of Israeli Populations, a biobank of genetic information about Israeli citizens located at TAU's Sackler Faculty of Medicine and directed by Dr. Gurwitz. The TAU researchers then analyzed and compared the RNA profiles of the most and least responsive cell lines. A gene called CHL1 was produced at lower levels in the most responsive cell lines and at higher levels in the least responsive cell lines. Using a simple genetic test, doctors could one day use CHL1 as a biomarker to determine whether or not to prescribe SSRIs.

"We want to end up with a blood test that will allow us to tell a patient which drug is best for him," said Oved. "We are at the early stages, working on the cellular level. Next comes testing on animals and people."

Rethinking how antidepressants work

The TAU researchers also wanted to understand why CHL1 levels might predict responsiveness to SSRIs. To this end, they applied Paroxetine to human cell lines for three weeks — the time it takes for a clinical response to SSRIs. They found that Paroxetine caused increased production of the gene ITGB3 — whose protein product is thought to interact with CHL1 to promote the development of new neurons and synapses. The result is the repair of dysfunctional signaling in brain regions controlling mood, which may explain the action of SSRI antidepressants.

This explanation differs from the conventional theory that SSRIs directly relieve depression by inhibiting the reabsorption of the neurotransmitter serotonin in the brain. Dr. Shomron adds that the new explanation resolves the longstanding mystery as to why it takes at least three weeks for SSRIs to ease the symptoms of depression when they begin inhibiting reabsorption after a couple days — the development of neurons and synapses takes weeks, not days.

The TAU researchers are working to confirm their findings on the molecular level and with animal models. Adva Hadar, a master's student in Dr. Gurwitz's lab, is using the same approach to find biomarkers for the personalized treatment of Alzheimer's disease.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,600+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
Tuesday, August 04, 2015
Reversing Antibiotic Resistance in Bacteria
Scientists at Tel Aviv University say they have developed a tool that tackles the problem of antibiotic resistance while also providing a new approach to combating bacterial infections.
Tuesday, June 09, 2015
Can Cancer Be Turned Against Itself?
Immune system can use melanoma's own proteins to kill off cancer cells, TAU researchers find.
Thursday, February 07, 2013
Scientific News
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Shaking Up the Foundations of Epigenetics
Researchers at the Centre for Genomic Regulation (CRG) and the University of Barcelona (UB) published a study that challenges some of the current beliefs about epigenetics.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
3 Ways Viruses Have Changed Science for the Better
Viruses are really good at what they do, and we’ve been able to harness their skills to learn about – and potentially improve – human health in several ways.
Mixed Up Cell Transportation Key Piece of ALS and Dementia Puzzle
Researchers from the University of Toronto are one step closer to solving this incredibly complex puzzle, offering hope for treatment.
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Five New Genetic Variants Linked to Brain Cancer Identified
The biggest ever study of DNA from people with glioma – the most common form of brain cancer – has discovered five new genetic variants associated with the disease.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos