Depression stems from miscommunication between brain cells, study shows

March 18, 2013, University of Maryland

A new study from the University of Maryland School of Medicine suggests that depression results from a disturbance in the ability of brain cells to communicate with each other. The study indicates a major shift in our understanding of how depression is caused and how it should be treated. Instead of focusing on the levels of hormone-like chemicals in the brain, such as serotonin, the scientists found that the transmission of excitatory signals between cells becomes abnormal in depression. The research, by senior author Scott M. Thompson, Ph.D., Professor and Interim Chair of the Department of Physiology at the University of Maryland School of Medicine, was published online in the March 17 issue of Nature Neuroscience.

According to the , between 2005 and 2008, approximately one in 10 Americans were treated for , with women more than twice as likely as men to become depressed. The most common antidepressant medications, such as Prozac, Zoloft and Celexa, work by preventing from absorbing serotonin, resulting in an increase in its concentration in the brain. Unfortunately, these medications are effective in only about half of patients. Because elevation of serotonin makes some feel better, it has been thought for over 50 years that the cause of depression must therefore be an insufficient level of serotonin. The new University of Maryland study challenges that long-standing explanation.

"Dr. Thompson's groundbreaking research could alter the field of psychiatric medicine, changing how we understand the crippling public health problem of depression and other mental illness," says E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs at the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor and Dean at the University of Maryland School of Medicine. "This is the type of cutting-edge science that we strive toward at the University of Maryland, where discoveries made in the laboratory can impact the clinical practice of medicine."

Depression affects more than a quarter of all U.S. adults at some point in their lives, and the World Health Organization predicts that by 2020 it will be the second leading cause of disability worldwide. Depression is also the leading risk factor for suicide, which causes twice as many deaths as murder, and is the third leading cause of death for 15-24 year olds.

The first major finding of the study was the discovery that serotonin has a previously unknown ability to strengthen the communication between brain cells. "Like speaking louder to your companion at a noisy cocktail party, serotonin amplifies excitatory interactions in brain regions important for emotional and cognitive function and apparently helps to make sure that crucial conversations between neurons get heard," says Dr. Thompson. "Then we asked, does this action of serotonin play any role in the therapeutic action of drugs like Prozac?"

To understand what might be wrong in the brains of patients with depression and how elevating serotonin might relieve their symptoms, the study team examined the brains of rats and mice that had been repeatedly exposed to various mildly stressful conditions, comparable to the types of psychological stressors that can trigger depression in people.

The researchers could tell that their animals became depressed because they lost their preference for things that are normally pleasurable. For example, normal animals given a choice of drinking plain water or sugar water strongly prefer the sugary solution. Study animals exposed to repeated stress, however, lost their preference for the sugar water, indicating that they no longer found it rewarding. This depression-like behavior strongly mimics one hallmark of human depression, called anhedonia, in which patients no longer feel rewarded by the pleasures of a nice meal or a good movie, the love of their friends and family, and countless other daily interactions.

A comparison of the activity of the animals' brain cells in normal and stressed rats revealed that stress had no effect on the levels of serotonin in the 'depressed' brains. Instead, it was the excitatory connections that responded to serotonin in strikingly different manner. These changes could be reversed by treating the stressed animals with antidepressants until their normal behavior was restored.

"In the depressed brain, serotonin appears to be trying hard to amplify that cocktail party conversation, but the message still doesn't get through," says Dr. Thompson. Using specially engineered mice created by collaborators at Johns Hopkins University School of Medicine, the study also revealed that the ability of serotonin to strengthen excitatory connections was required for drugs like antidepressants to work.

Sustained enhancement of communication between brain cells is considered one of the major processes underlying memory and learning. The team's observations that excitatory brain cell function is altered in models of depression could explain why people with depression often have difficulty concentrating, remembering details, or making decisions. Additionally, the findings suggest that the search for new and better antidepressant compounds should be shifted from drugs that elevate serotonin to drugs that strengthen excitatory connections.

"Although more work is needed, we believe that a malfunction of excitatory connections is fundamental to the origins of depression and that restoring normal communication in the brain, something that apparently does in successfully treated patients, is critical to relieving the symptoms of this devastating disease," Dr. Thompson explains.

Explore further: Scientists revisit biochemical basis for depression

Related Stories

Scientists revisit biochemical basis for depression

February 12, 2013
Symptoms of depression and anxiety can be induced in mice by increasing levels of acetylcholine, suggesting that depression may have different biochemical roots than previously believed, Yale School of Medicine researchers ...

Studies seek better understanding and treatment of depression

August 14, 2012
Connecting the dots between two molecules whose levels are decreased in depression and increased by current antidepressants could yield new therapies, researchers say.

Recommended for you

Cognitive training helps regain a younger-working brain

January 23, 2018
Relentless cognitive decline as we age is worrisome, and it is widely thought to be an unavoidable negative aspect of normal aging. Researchers at the Center for BrainHealth at The University of Texas at Dallas, however, ...

Lifting the veil on 'valence,' brain study reveals roots of desire, dislike

January 23, 2018
The amygdala is a tiny hub of emotions where in 2016 a team led by MIT neuroscientist Kay Tye found specific populations of neurons that assign good or bad feelings, or "valence," to experience. Learning to associate pleasure ...

Your brain responses to music reveal if you're a musician or not

January 23, 2018
How your brain responds to music listening can reveal whether you have received musical training, according to new Nordic research conducted in Finland (University of Jyväskylä and AMI Center) and Denmark (Aarhus University).

New neuron-like cells allow investigation into synthesis of vital cellular components

January 22, 2018
Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers ...

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.


Adjust slider to filter visible comments by rank

Display comments: newest first

4 / 5 (4) Mar 18, 2013
This might explain why sometimes a medication will seem to be working and then the benefits level off. The med increases serotonin for a time which briefly increases exitatory connections but the cells respond to the extra serotonin by producing less via some negative feedback effect, leaving at best a slight increase and a dependency (not addiction) on the med (going off SSRIs cold can be very unpleasant). The serotonin levels are not the cause of the problem but only mitigate the problem somewhat when raised. For some the mitigation is sufficient while others just adapt to the change and the depression continues.
4.5 / 5 (8) Mar 18, 2013
"approximately one in 10 Americans were treated for depression, with women more than twice as likely as men to become depressed.

As much as I understand the desire to paint depression as a women's issue so it can be taken seriously, women are more likely to *report* depression. Men report depression most often with a bullet in the brain which moves them into a separate statistic of "suicide"; a stat for which men out number women 4 times over. That also doesn't count the men who don't *report* depression or commit suicide but use other means of self-treatment like drinking themselves to death. Continuously portraying depression as something that more often affects women reinforces the message that it is unmanly to admit depression so it isn't a harmless little white lie.
3 / 5 (2) Mar 18, 2013
Whenever we hear the blanket term 'depression' followed by suggested generalisation we can be sure that complete rubbish follows.

Firstly, there is the typical (low effect, emotional depression) and atypical (no low effect, no emotional depression), different profiles such as continuous and unipolar, cyclic (e.g. in winter only) and so on.

Further, although all forms of depression may trigger the same mechanisms, such as low serotonin levels, low levels per say may or may not be the cause e.g. if a person is placed in a depressive environment for long enough they will have the same low serotonin levels that a person suffering MDD will have.

Thus if there is no specific constraint on the form of depression being considered then placebos and witchcraft can be included as effective treatments with just as much (or lack of) authority.
4 / 5 (4) Mar 19, 2013
Studying how club drug ketamine halts depression for weeks after a single dose should be a priority but for Drug War red tape, since it's a hallucinogen.
5 / 5 (2) Mar 19, 2013
Robert, I don't know what you're getting at. All forms of depression, whether caused by a bad situation or a bad season have the same basic neuropathology in the brain: i.e. atrophied hippocampus, overwired prefrontal cortex, and a breakdown of communication between neurons. The idea that different types of depression (of which there are many) will look very different biologically just hasn't been borne out in research.

Nik, I agree, assuming Ketamine *really* is a very effective anti-depressant (looking like it currently but jury still out), it's a crime the DEA and feds will never allow it to be used outside a hospital setting because idiots might use it to get high. ECT is arguably much more dangerous. You're not going to tell me we couldn't setup special Ketamine clinics for those who really need it, and administer the drug IV. With such oversight there'd be no chance of abuse, but it'll probably never be considered in America.
not rated yet Mar 24, 2013
The statement "depression results from a disturbance in the ability of brain cells to communicate with each other." is totally unsustainable. Depression can be caused or even induced by life circumstances, drugs, poor health and so on. These forms can occur within a few hours or even a few minutes in an otherwise happy individual.

For instance hearing about the death of one's parent causes instant and profound depression which lasts for weeks. Can "atrophied hippocampus, overwired prefrontal cortex" occur in seconds??? I doubt it.

The kind of depression that may be relevant to the observations in the article are persistent depression of the kind that would be diagnosed as MDD. Thus it is important to state this. For instance, would unipolar depression with as few as two or three depressive episodes per year also result in the reported neural phenomena (or be caused by it)???

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.