Depression stems from miscommunication between brain cells, study shows
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 Centers for Disease Control and Prevention, between 2005 and 2008, approximately one in 10 Americans were treated for depression, 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 brain cells 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 depressed patients 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 serotonin apparently does in successfully treated patients, is critical to relieving the symptoms of this devastating disease," Dr. Thompson explains.
Journal reference: Nature Neuroscience
Provided by University of Maryland
- Scientists revisit biochemical basis for depression Feb 12, 2013 | not rated yet | 0
- Are older antidepressants better for depression in Parkinson's disease? Dec 17, 2008 | not rated yet | 0
- Research suggests mechanism for acne drug's link to depression Nov 12, 2007 | not rated yet | 0
- Studies seek better understanding and treatment of depression Aug 14, 2012 | not rated yet | 0
- Sex differences in the brain's serotonin system Feb 13, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
5 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
A study from the June issue of Anesthesiology found feedback from the front region of the brain is a crucial building block for consciousness and that its disruption is associated with unconsciousness when the anesthetics ketami ...
Neuroscience 24 minutes ago | not rated yet | 0
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
Neuroscience 16 hours ago | 4.3 / 5 (3) | 0 |
Moving objects attract greater attention – a fact exploited by video screens in public spaces and animated advertising banners on the Internet. For most animal species, moving objects also play a major ...
Neuroscience 19 hours ago | not rated yet | 0 |
It is known that signs of neurological disorders such as Alzheimer's and Huntington's disease can appear years before the disease becomes manifest; these signs take the form of subtle changes in the brain and behavior of ...
Neuroscience 19 hours ago | not rated yet | 0
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with ...
Neuroscience 21 hours ago | 5 / 5 (2) | 0 |
For the first time, physicists from the Max Planck Institute for Extraterrestrial Physics (MPE), biologists and physicians demonstrated the synergistic effect of cold atmospheric plasma - a partly ionized ...
24 minutes ago | not rated yet | 0 |
As health services strive to improve quality and reduce costs, researchers study the benefits – and the pitfalls – of 'pay for performance' in hospitals.
33 minutes ago | not rated yet | 0 |
(Medical Xpress)—Scientists from the Joint Center for Structural Genomics (JCSG) at SLAC National Accelerator Laboratory have determined the 3-D structure of the chemically active part of an enzyme involved ...
4 minutes ago | not rated yet | 0 |
(Medical Xpress)—According to the World Health Organization, approximately 70 million couples experience infertility worldwide. Current data suggests that nearly one third of infertility disorders are due ...
44 minutes ago | not rated yet | 0
(Medical Xpress)—There is no significant risk directly associated with air travel during pregnancy, even at advanced gestation, says report by the University of Liverpool.
54 minutes ago | not rated yet | 0
Parents naturally are concerned for their children's safety, particularly when there is news of a child abduction that happens close to home. Finding the balance between emotions and the "teachable moment" as parents talk ...
14 minutes ago | not rated yet | 0