Nav: Home

New research points to better way to treat depression

March 01, 2018

JUPITER, FL - March 1, 2018 - Scientists on the Florida campus of The Scripps Research Institute (TSRI) have discovered a new target for treating major depressive disorder, a disease that affects more than 16 million American adults. Their research shows that individuals with high levels of an enigmatic receptor called GPR158 may be more susceptible to depression following chronic stress.

"The next step in this process is to come up with a drug that can target this receptor," says Kirill Martemyanov, PhD, co-chair of the TSRI Department of Neuroscience and senior author of the new study, published recently in the journal eLife.

The researchers say there is an urgent need for new drug targets in major depressive disorder. Current pharmacological treatments for depression can take a month to start working--and they don't work in all patients.

"We need to know what is happening in the brain so that we can develop more efficient therapies," says Cesare Orlandi, PhD, senior research associate at TSRI and co-first author of the study.

The researchers zeroed in on GPR158 as a player in depression after discovering that the protein is elevated in people with major depressive disorder. To better understand GPR158's role, the scientists studied male and female mice with and without GPR158 receptors.

Behavioral tests revealed that both male and female mice with elevated GPR158 show signs of depression following chronic stress. On the flip side, suppression of GPR158 protects mice from developing depressive-like behaviors and make them resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called "orphan receptor" (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain's inhibitory control and adrenergic system involved in stress effects.

"This is really new biology and we still need to learn a lot," says Martemyanov.

The study also offers a potential clue to why some people are more susceptible to mental illness. Because mice without GPR158 don't alter their behavior after chronic stress, the researchers concluded these mice were naturally more resilient against depression. Their genetics, or gene expression, offer a layer of protection.

Laurie Sutton, PhD, a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. "There's always a small population that is resilient--they don't show the depressive phenotype," says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists areincreasingly using new tools in genome analysis to identify orphan receptors like GPR158. "Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics," he says.
-end-
Additional authors of the study, "Orphan receptor GPR158 controls stress-induced depression," were Chenghui Song, Brian S. Muntean, Keqiang Xie, Xiangyang Xie and Baoji Xu of The Scripps Research Institute; Won Chan Oh and Rachel Satterfield of the Max Planck Florida Institute for Neuroscience; Alice Filippini of the University of Brescia; Jazmine D. W. Yaeger and Kenneth J. Renner of the University of South Dakota; Samuel M. Young of the Max Planck Florida Institute for Neuroscience and the University of Iowa; and Hyungbae Kwon of the Max Planck Florida Institute for Neuroscience and the Max Planck Institute of Neurobiology.

The research was supported by the National Institutes of Health (grants MH105482, HL105550, DA01992, MH107460, 762 DC014093, the University of Iowa, the Max Planck Society and by the Canadian Institutes of Health Research Fellowship.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.

Scripps Research Institute

Related Depression Articles:

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.
Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.
Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.
CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.
Post-natal depression in dads linked to depression in their teenage daughters
Fathers as well as mothers can experience post-natal depression -- and it is linked to emotional problems for their teenage daughters, new research has found.
Being overweight likely to cause depression, even without health complications
A largescale genomic analysis has found the strongest evidence yet that being overweight causes depression, even in the absence of other health problems.
Don't let depression keep you from exercising
Exercise may be just as crucial to a depression patient's good health as finding an effective antidepressant.
Having an abortion does not lead to depression
Having an abortion does not increase a woman's risk for depression, according to a new University of Maryland School of Public Health-led study of nearly 400,000 women.
Mother's depression might do the same to her child's IQ
Roughly one in 10 women in the United States will experience depression, according to the Centers for Disease Control and Prevention.
Teenage depression linked to father's depression
Adolescents whose fathers have depressive symptoms are more likely to experience symptoms of depression themselves, finds a new Lancet Psychiatry study led by UCL researchers.
More Depression News and Depression Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.