... from universities, journals, and other research organizations
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. (Credit: © Artur Golbert / Fotolia)
Mar. 18, 2013 — 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.
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