Scientists find new path in brain to ease depression

October 5, 2016, Northwestern University
Credit: CC0 Public Domain

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 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' 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 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 .

"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."

Explore further: New antidepressant target discovered

Related Stories

New antidepressant target discovered

July 12, 2016
Northwestern Medicine scientists have shown how manipulating a novel target in the brain using gene therapy could lead to new treatments for depression.

How do antidepressants trigger fear and anxiety?

August 24, 2016
More than 100 million people worldwide take selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Zoloft, to treat depression, anxiety and related conditions, but these drugs have a common and mysterious side ...

How depression and antidepressant drugs work

May 18, 2016
New research demonstrates the effectiveness of ketamine to treat depression in a mouse model of the disease and brings together two hypotheses for the cause of depression. The research, led by Bernhard Lüscher, professor ...

Exploring the antidepressant effects of testosterone

April 2, 2012
Testosterone, the primary male sex hormone, appears to have antidepressant properties, but the exact mechanisms underlying its effects have remained unclear. Nicole Carrier and Mohamed Kabbaj, scientists at Florida State ...

Move over Prozac: New drug offers hope for depression

April 18, 2011
The brain chemistry that underlies depression is incompletely understood, but research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor through its receptor TrkB, may contribute to anxiety ...

Serotonin-deficient brains more vulnerable to social stress

February 9, 2015
Mice genetically deficient in serotonin—a crucial brain chemical implicated in clinical depression—are more vulnerable than their normal littermates to social stressors, according to a Duke study appearing this week in ...

Recommended for you

Young children use physics, not previous rewards, to learn about tools

February 23, 2018
Children as young as seven apply basic laws of physics to problem-solving, rather than learning from what has previously been rewarded, suggests new research from the University of Cambridge.

Study: Tinder loving cheaters—dating app facilitates infidelity

February 23, 2018
The popular dating app Tinder is all about helping people form new relationships. But for many college-aged people, it's also helping those in relationships cheat on their romantic partners.

Looking for the origins of schizophrenia

February 23, 2018
Schizophrenia may be related to neurodevelopmental changes, including brain's inability to generate an appropriate vascular system, according to new study resulted from a partnership between the D"Or Institute for Research ...

Color of judo uniform has no effect on winning

February 22, 2018
New research on competitive judo data finds a winning bias for the athlete who is first called, regardless of the colour of their uniform. This unique study, published in Frontiers in Psychology, puts to rest the debate on ...

Antidepressants are more effective than placebo at treating acute depression in adults, concludes study

February 22, 2018
Meta-analysis of 522 trials includes the largest amount of unpublished data to date, and finds that antidepressants are more effective than placebo for short-term treatment of acute depression in adults.

Infants are able to learn abstract rules visually

February 22, 2018
Three-month-old babies cannot sit up or roll over, yet they are already capable of learning patterns from simply looking at the world around them, according to a recent Northwestern University study published in PLOS One.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

manifespo
not rated yet Oct 06, 2016
Noodle Scratching my brain's Noggin Proteins

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.