Although medications exist to treat depression, many scientists arent sure why theyre effective and why they dont work for everyone.
Researchers at the University of Maryland School of Medicine believe they may have found a key to the puzzle of major depression that could lead to therapies for those who dont respond to medications already on the market.
A new study by the researchers has identified the central role a gene known as Slc6a15 plays in either protecting from stress or contributing to depression, depending on its level of activity in a part of the brain associated with motivation, pleasure and reward seeking.
Published in the Journal of Neuroscience in July, the study is the first to illuminate in detail how the gene works in a kind of neuron that plays a key role in depression, according to the University of Maryland School of Medicine.
Specifically, the researchers found that mice with depression had reduced levels of the genes activity, while those with high levels of the genes activity handled chronic stress better.
Though senior researcher Mary Kay Lobos primary studies were done with mice, she also examined the brains of people who had committed suicide and found reduced levels of the genes activity, confirming a likely link.
She hopes now that drugs could be developed that would encourage the genes activity.
I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interested in how it becomes dysfunctional in certain diseases like depression, Lobo said. I hope that we can identify molecules that could potentially be therapeutically treated or targeted to treat depression.
Lobo and her colleagues have been examining the gene for years. In 2006, they discovered that it was more common among specific neurons in the brain that they later learned were related to depression. Five years later, other researchers learned the gene played a role in depression and Lobo and her research colleagues decided to investigate what that role is in those specific neurons.
About 15 million adults, or 6.7 percent of all U.S. adults, experience major depression in a given year, according to the Anxiety and Depression Association of America. It is the leading cause of disability for Americans aged 15 to 44. It is more prevalent in women and can develop at any age, but the median age of onset is 32.5.
David Dietz, an associate professor in the Department of Pharmacology and Toxicology at the State University of New York at Buffalo, said little was known previously about the biological basis of depression in the brain. Many drugs used to treat depression were discovered serendipitously, he said, and it wasnt clear why they worked.
Were starting to really get an idea of what does the depressed brain look like, Dietz said. When you put the whole puzzle together, you see where the problem is. For too long weve been throwing things at individual pieces. Its so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.
Lobo said its not clear yet how Slc6a15 works in the brain, but she believes it may be transporting three types of amino acids into a subset of neurons called D2 neurons in a part of the brain called the nucleus accumbens. The nucleus accumbens and D2 neurons are known to play a role in pleasure, activating when one eats a delicious meal, has sex or drinks alcohol.
The amino acids would then be synthesized into neurotransmitters. Depression previously has been linked to imbalances of the neurotransmitters serotonin, norepinephrine and dopamine.
So even though people may have proper levels of amino acids in their bodies, the neurons in their brains that need them may not be getting enough if the transporter is not working as it should.
This gene is critical for putting very specific amino acids in the right place so that neurotransmitters can be synthesized, said A.J. Robison, an assistant professor in the Department of Physiology at Michigan State University. Its the location, location, location idea. Its not the amino acids, its where theyre at and in which cells.
Robison said Lobos next step would be discovering more about how the transporter gene works.
The fact that this transporter seems to be important is what the paper shows and how it does it is not shown, and thats a challenge for her, he said. Figuring out the how of it is the next step and Dr. Lobo is particularly positioned to do it.
Lobos team was able to use gene therapy, a form of therapy in the early stages of being studied in humans, in the mice to boost the genes activity. The mice were exposed to larger, more aggressive mice, which usually causes depressive symptoms. But the gene therapy helped protect the mice against the stress, the team found. When the team reduced the genes activity in the mice, just one day of exposure to the aggressive mice was enough to cause symptoms of depression.
Gene therapy is starting to be used in the treatment of some types of cancers, but Lobo said science had not yet advanced to the point where it can be used for treating neurological issues in human patients. A more likely treatment would be a drug that targets the genes activity directly, she said.
I think this is a major step toward our understanding of the precise maladaptive changes that occur in response to stress, said Vanna Zachariou, an associate professor in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. It can be a more efficient way to target depression because its not simply targeting monoamine receptors or dopamine but targeting molecular adaptations that occur. It doesnt act necessarily as the drugs we have available, so it might create an alternative avenue to treat depression.
Lobo said she wouldnt refer to Slc6a15 as a depression gene, saying the disease was complex and could have many factors.
I wouldnt say theres one depression gene she said. A number of things play a role, and also theres no depression neuron, theres multiple depression neurons.
There also may be different types of depression with different symptoms, she said. With the disease, some sufferers sleep a lot, while others sleep a lot less, for example.
With all these complex diseases, its hard to link it to something, she said. Like Huntingtons disease, we know theres a specific gene that causes Huntingtons disease. For depression we dont have that.
See more here:
University of Maryland scientists research gene linked to depression - Baltimore Sun
- About the Gene Therapy Review - November 8th, 2009 [November 8th, 2009]
- Contribute an Article - November 8th, 2009 [November 8th, 2009]
- EBSCO Publishing Deal - November 8th, 2009 [November 8th, 2009]
- Advertising Opportunities - November 8th, 2009 [November 8th, 2009]
- Instructions for Authors - November 8th, 2009 [November 8th, 2009]
- Isis Collaboration With Ortho-McNeil Inc for Metabolic Diseases - November 8th, 2009 [November 8th, 2009]
- Dystrophin Gene Transfer safe in Duchenne muscular dystrophy - November 8th, 2009 [November 8th, 2009]
- Researchers Identify Gene for Rare Form of Spinal Muscular Atrophy - November 8th, 2009 [November 8th, 2009]
- Fatal brain cancer tamed by New gene therapy - November 8th, 2009 [November 8th, 2009]
- Gene therapy effective in fighting obesity in mice - November 8th, 2009 [November 8th, 2009]
- Genzyme gene therapy for people with peripheral artery disease failed in a clinical trial to help them regain some mobility - November 8th, 2009 [November 8th, 2009]
- Gene Therapy May Stall Inherited Emphysema - December 31st, 2009 [December 31st, 2009]
- Gene Therapy and Stem Cells Save Limb - December 31st, 2009 [December 31st, 2009]
- TNVitamins.com – $10 Off Of $50 order - May 7th, 2011 [May 7th, 2011]
- 15% Off Any PetAlive Order - May 7th, 2011 [May 7th, 2011]
- At PetAlive – $10 off order of $50 or more - May 7th, 2011 [May 7th, 2011]
- Native Remedies coupon – 5% Off Any Order - May 7th, 2011 [May 7th, 2011]
- Native Remedies – Save $5 coupon - May 7th, 2011 [May 7th, 2011]
- Welcome to the Gene Therapy Review - May 15th, 2011 [May 15th, 2011]
- Editorial Board - May 15th, 2011 [May 15th, 2011]
- Gene Therapy Job Board - May 15th, 2011 [May 15th, 2011]
- Corporate Membership - May 22nd, 2011 [May 22nd, 2011]
- Native Remedies coupon – 25% Off Any Order - May 29th, 2011 [May 29th, 2011]
- What is Gene Therapy? - June 19th, 2011 [June 19th, 2011]
- Research and Markets: Recent Advances in Cancer Research and Therapy - Increased Research on one of the Major Causes ... - April 25th, 2012 [April 25th, 2012]
- Gene Therapy part 2 - Video - April 30th, 2012 [April 30th, 2012]
- Gene therapy reverses Parkinson's symptoms: study - Video - April 30th, 2012 [April 30th, 2012]
- CBS This Morning - Gene therapy reverses Parkinson's symptoms: study - Video - April 30th, 2012 [April 30th, 2012]
- Engineering adenoviruses for gene therapy - Video - April 30th, 2012 [April 30th, 2012]
- What is Gene Therapy (The General Explains) - Video - April 30th, 2012 [April 30th, 2012]
- What is Gene Therapy - Animation - Video - April 30th, 2012 [April 30th, 2012]
- Microbiology Gene Therapy - Video - April 30th, 2012 [April 30th, 2012]
- Gene Therapy in Detail - Video - April 30th, 2012 [April 30th, 2012]
- Breakthrough in Haemophilia treatment - Video - April 30th, 2012 [April 30th, 2012]
- Virology Seminar - Gene Therapy - April 30th, 2012 [April 30th, 2012]
- Gene Therapy Video - Video - April 30th, 2012 [April 30th, 2012]
- Study: Gene Therapy for HIV Safe, But Effectiveness Still Unclear - May 4th, 2012 [May 4th, 2012]
- Gene Therapy Safe in Decade-Long HIV Study That May Widen Use - May 4th, 2012 [May 4th, 2012]
- Gene therapy for HIV safe, but effectiveness still unclear - May 4th, 2012 [May 4th, 2012]
- A Step Forward For Gene Therapy To Treat HIV - May 4th, 2012 [May 4th, 2012]
- A Media Event on Clinical Developments in Gene and Cell Therapy - May 4th, 2012 [May 4th, 2012]
- Families of SMA Awards New Funding to Advance a CNS Delivered Gene Therapy for Spinal Muscular Atrophy - May 4th, 2012 [May 4th, 2012]
- AIDS gene therapy safe -- is it a "cure"? - May 4th, 2012 [May 4th, 2012]
- Generational Achievements in Gene and Cell Therapy Honored at ASGCT 15th Annual Meeting - May 5th, 2012 [May 5th, 2012]
- Lewis speaks on gene therapy at Lexington Community Education event - May 7th, 2012 [May 7th, 2012]
- Penn researchers report a gene-therapy success - May 10th, 2012 [May 10th, 2012]
- Gene therapy for hearing loss: Potential and limitations - May 13th, 2012 [May 13th, 2012]
- Gene therapy extends mouse lifespan by 24 pc - May 16th, 2012 [May 16th, 2012]
- Gene therapy dramatically extends mouse lifespan - May 16th, 2012 [May 16th, 2012]
- Gene therapy may extend life: Study - May 16th, 2012 [May 16th, 2012]
- First gene therapy successful against aging-associated decline: Mouse lifespan extended up to 24% with a single ... - May 16th, 2012 [May 16th, 2012]
- Gene Therapy Extends Mouse Lifespan - May 16th, 2012 [May 16th, 2012]
- Gene Therapy for Brain Disease - May 17th, 2012 [May 17th, 2012]
- Children with rare, incurable brain disease improve after gene therapy - May 17th, 2012 [May 17th, 2012]
- FIRST Anti-Aging Gene Therapy (Brainstorm Ep72) - Video - May 23rd, 2012 [May 23rd, 2012]
- Gene therapy can correct forms of severe combined immunodeficiency - May 25th, 2012 [May 25th, 2012]
- RetroSense Therapeutics Completes pre-IND Meeting for RST-001 - May 25th, 2012 [May 25th, 2012]
- Gene therapy can correct forms of severe combined immunodeficiency, study suggests - May 26th, 2012 [May 26th, 2012]
- Alliance for Cancer Gene Therapy celebrates 10 years - May 29th, 2012 [May 29th, 2012]
- Research on gene therapy by Prasad Eye - June 1st, 2012 [June 1st, 2012]
- Baxter Announces Collaboration with Chatham Therapeutics for Factor IX Hemophilia B Gene Therapy Treatment - June 5th, 2012 [June 5th, 2012]
- Transgenomic Launches Breakthrough Blood-Based Cancer Gene Testing Technology at 2012 ASCO Annual Meeting - June 5th, 2012 [June 5th, 2012]
- Baxter Inks Deal with Chatham - June 6th, 2012 [June 6th, 2012]
- PIK3CA Gene Patent for Predicting Response to Targeted Therapy Issued – Exclusively Licensed to Transgenomic - June 11th, 2012 [June 11th, 2012]
- SalutarisMD Announces Positive Case Report of a New Investigational Wet AMD Therapy at ARVO - June 15th, 2012 [June 15th, 2012]
- Research and Markets: Gene Therapy - Global Strategic Business Report - 2012 - June 15th, 2012 [June 15th, 2012]
- New York Law Firm’s MesotheliomaHelp.net Site Publishes Interview with Gene Therapy Author - June 17th, 2012 [June 17th, 2012]
- uniQure Extends Collaboration with Protein Sciences Corporation on Use of its expresSF+® Cell Line for Gene Therapy - June 19th, 2012 [June 19th, 2012]
- Anti-cocaine vaccine described in Human Gene Therapy Journal - June 19th, 2012 [June 19th, 2012]
- bluebird bio Receives U.S. and European Orphan Drug Designation for Novel Gene Therapy to Treat Adrenoleukodystrophy - June 19th, 2012 [June 19th, 2012]
- Close to a cure: Greater Hartford takes on rare Jewish genetic disease - June 19th, 2012 [June 19th, 2012]
- Gene Therapy Helps Treat Children with Rare Brain Disorder - June 20th, 2012 [June 20th, 2012]
- Gold nanoparticles capable of 'unzipping' DNA - June 21st, 2012 [June 21st, 2012]
- ‘Gene-silencing’ drug can halt and reverse deadly brain disorder - June 21st, 2012 [June 21st, 2012]
- uniQure Collaborates with UCSF on GDNF Gene Therapy in Parkinson's Disease - June 22nd, 2012 [June 22nd, 2012]
- Gene-silencing method offers possible therapy for Huntington's disease - June 22nd, 2012 [June 22nd, 2012]
- Gene mutations cause massive brain asymmetry - June 24th, 2012 [June 24th, 2012]
- Research and Markets: Translational Regenerative Medicine - Oncology, CNS and Cardiovascular-Rich Pipeline Features ... - June 25th, 2012 [June 25th, 2012]
- Stress Blocks Gene That Guards Brain Against Depression - June 26th, 2012 [June 26th, 2012]
- Targeted gene therapy enhances treatment for Pompe disease - June 26th, 2012 [June 26th, 2012]