A New Discovery Could Change Future Diagnosis
And Therapy Of Depression
March 12, 2008
Researchers from the University of Illinois at Chicago College of Medicine have
discovered that a change in the location of a protein in the brain could serve
as a biomarker for depression, allowing a simple, rapid, laboratory test to
identify patients with depression and to determine whether a particular
antidepressant therapy will provide a successful response.
The research is published in the March 12 issue of the Journal of Neuroscience.
"This test could serve to predict the efficacy of antidepressant therapy
quickly, within four to five days, sparing patients the agony of waiting a month
or more to find out if they are on the correct therapeutic regimen," said
Mark Rasenick, UIC distinguished university professor of physiology and
biophysics and psychiatry.
Despite decades of research, the biological basis of depression is unknown, and
the molecular and cellular targets of antidepressant treatment remain elusive,
although it is likely that these drugs have one or more primary targets.
Rasenick said the discovery could help millions who suffer from undiagnosed
depression or receive unsuccessful treatment.
"We discovered that in depressed individuals a signaling protein is located
in specific areas of the cell membrane called lipid rafts," he said. This
protein, called Gs alpha, activates adenylyl cyclase, a link in signal
transduction, and is responsible for the action of neurotransmitters such as
serotonin.
"These 'rafts' are thick, viscous, almost gluey areas, that either
facilitate or impede communication between membrane molecules," Rasenick
said. "When Gs alpha is caught in these lipid raft domains, its ability to
couple with and activate adenylyl cyclase is markedly reduced. Antidepressants
help to move the Gs alpha out of these rafts and facilitate the action of
certain neurotransmitters."
Previous research in both rats and cultured brain cells by Rasenick and his
colleagues, as well as others, has shown that Gs alpha changed its location in
response to antidepressants, moving out of the lipid rafts to areas of the
membrane that allow more efficient communication among membrane components
responsible for neurotransmitter action. Further, antidepressant and
antipsychotic drugs have been shown to concentrate in these lipid rafts.
"This new study shows that in depressed humans, Gs alpha protein is
confined in lipid rafts, where it's less likely to mediate the action of
neurotransmitters, and that antidepressants have the opposite effect,"
Rasenick said.
"In simple language -- we may be able to tell you if you are depressed and
more importantly, whether you are responding to the chosen antidepressant
therapy."
The new study may also explain why antidepressants take so long to work and why
chemically dissimilar compounds have similar effects.
In their study, Rasenick and colleagues compared brain samples from depressed
people who had committed suicide with controls who had no history of psychiatric
disorders. They found that while the total amount of Gs alpha was the same in
the depressed and non-depressed, the depressed have a greater proportion of Gs
alpha confined to lipid rafts. The localization of other G proteins was not
different.
Rasenick and his colleagues have begun further studies to confirm and expand
these findings.
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Article adapted by Medical News Today from original press release.
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The study was supported by grants from the U.S. Public Health Service and the
American Foundation for Suicide Prevention.
Robert Donati, Yogesh Dwivedi and Ghanshyam Pandey from UIC College of Medicine
and Rosalinda Roberts and Robert Conley from the Maryland Psychiatric Research
Center in Baltimore contributed to this study. Donati is also on the faculty of
the Illinois College of Optometry.
UIC ranks among the nation's top 50 universities in federal research funding and
is Chicago's largest university with 25,000 students, 12,000 faculty and staff,
15 colleges and the state's major public medical center. A hallmark of the
campus is the Great Cities Commitment, through which UIC faculty, students and
staff engage with community, corporate, foundation and government partners in
hundreds of programs to improve the quality of life in metropolitan areas around
the world.
For more information about UIC, visit http://www.uic.edu/.
Source: Jeanne Galatzer-Levy
Medical News Today: http://www.medicalnewstoday.com
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