Nav: Home

Scientists find new path in brain to ease depression

October 05, 2016

  • Many with depression are not helped by current drugs
  • Brain pathway with key role in depression discovered
  • New molecule blocks pathway and generates neurons, easing depression in mice
CHICAGO --- Northwestern Medicine scientists have discovered a new pathway in the brain that can be manipulated to alleviate depression. The pathway offers a promising new target for developing a drug that could be effective in individuals for whom other antidepressants have failed.

New antidepressant options are important because a significant number of patients don't adequately improve with currently available antidepressant drugs. The lifetime prevalence of major depressive disorder is between 10 to 20 percent of the population.

The study was published Oct. 4 in the journal Molecular Psychiatry.

"Identifying new pathways that can be targeted for drug design is an important step forward in improving the treatment of depressive disorders," said Sarah Brooker, the first author and an M.D./Ph.D student at Northwestern University Feinberg School of Medicine.

Brooker did the research in the lab of senior study author Dr. Jack Kessler, a professor of neurology at Feinberg and a Northwestern Medicine neurologist.

The aim of the study was to better understand how current antidepressants work in the brain. The ultimate goal is to find new ones that are more effective for people not currently getting relief from existing drugs.

In the study, scientists discovered for the first time that antidepressant drugs such as Prozac and tricyclics target a pathway in the hippocampus called the BMP signaling pathway. A signaling pathway is a group of molecules in a cell that work together to control one or more cell functions. Like a cascade, after the first molecule in a pathway receives a signal, it activates another molecule and so forth until the cell function is carried out.

Brooker and colleagues showed that Prozac and tricyclics inhibit this pathway and, thereby, trigger stem cells in the brain to produce more neurons. These particular neurons are involved in mood and memory formation. But the scientists didn't know if blocking the pathway contributed to the drugs' antidepressant effect because Prozac acts on multiple mechanisms in the brain.

After confirming the importance of the BMP pathway in depression, Northwestern scientists tested a brain protein, Noggin, on depressed mice. Noggin is known block the BMP pathway and stimulate new neurons, called neurogenesis.

"We hypothesized it would have an antidepressant effect, but we weren't sure," Brooker said.

They discovered Noggin blocks the pathway more precisely and effectively than Prozac or tricyclics. It had a robust antidepressant effect in mice.

Scientists injected Noggin into the mice and observed the effect on mood by testing for depression and anxiety behavior. A sign of depression in mice is a tendency to hang hopelessly when held by the tail, rather than trying to get upright. After receiving Noggin, mice energetically tried to lift themselves up, whereas control mice were more likely to give up and become immobile.

The mice were then put in a maze with secluded (safe) and open (less safe) spaces. The Noggin mice were less anxious and explored more mazes than the control mice.

"The biochemical changes in the brain that lead to depression are not well understood, and many patients fail to respond to currently available drugs," said Kessler, also the Ken and Ruth Davee Professor of Stem Cell Biology. "Our findings may not only help to understand the causes of depression, but also may provide a new biochemical target for developing more effective therapies."

The title of the paper is "Hippocampal bone morphogenetic protein signaling mediates behavioral effects of antidepressant treatment."
-end-
The study was funded by National Institute of Neurological Disorders and Stroke grants R01NS020778 and F31NS089154 from the National Institutes of Health and the Davee Foundation.

Northwestern University

Related Depression Articles:

Tackling depression by changing the way you think
A thought is a thought. It does not reflect reality.
How depression can muddle thinking
Depression is associated with sadness, fatigue and a lack of motivation.
Neuroimaging categorizes 4 depression subtypes
Patients with depression can be categorized into four unique subtypes defined by distinct patterns of abnormal connectivity in the brain, according to new research from Weill Cornell Medicine.
Studies suggest inflammatory cytokines are associated with depression and psychosis, and that anti-cytokine treatment can reduce depression symptoms
Studies presented at this year's International Early Psychosis Association meeting in Milan, Italy, (Oct.
Is depression in parents, grandparents linked to grandchildren's depression?
Having both parents and grandparents with major depressive disorder was associated with higher risk of MDD for grandchildren, which could help identify those who may benefit from early intervention, according to a study published online by JAMA Psychiatry.
More Depression News and Depression Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...