Brain images reveal effects of antidepressants
Feb. 7, 2003
MADISON - The experiences of millions of people have proved that
antidepressants work, but only with the advent of sophisticated imaging
technology have scientists begun to learn exactly how the medications affect
brain structures and circuits to bring relief from depression.
Researchers at the University of Wisconsin-Madison and UW Medical School
recently added important new information to the growing body of knowledge.
For the first time, they used functional magnetic resonance imaging
(fMRI)--technology that provides a view of the brain as it is working--to
see what changes occur over time during antidepressant treatment while
patients experience negative and positive emotions.
The study appears in the January issue of the American Journal of
Psychiatry. UW psychology professor Richard Davidson, Ph.D., psychiatry
department chair Ned Kalin, MD, research associate William Irwin and
research assistant Michael Anderle were the authors.
The researchers found that when they gave the antidepressant venlafaxine
(Effexor(r)) to a small group of clinically depressed patients, the drug
produced robust alterations in the anterior cingulate. This area of the
brain has to do with focused attention and also becomes activated when
people face conflicts. Unexpectedly, the changes were observed in just two
weeks.
"Conducting repeated brain scans in these patients allowed us to see for
the first time how quickly antidepressants work on brain mechanisms," said
Davidson, who also is director of the W. M. Keck Laboratory for Functional
Brain Imaging and Behavior, where imaging for the study took place. He noted
that the findings were surprising because patients don't usually begin
noticing mood improvements until after they have been taking antidepressants
for three to five weeks.
The researchers also found that while the depressed patients displayed
lower overall activity in the anterior cingulate than non-depressed
controls, those depressed patients who showed relatively more activity
before treatment responded better to the medication than those with lower
pre-treatment activity. This kind of information may be extremely useful to
clinicians someday, Kalin said.
"We expect that physicians in the future will be able to predict which
patients will be the best candidates for antidepressants simply by looking
at brain scans that reveal this type of pertinent information," said Kalin,
who also is director of the HealthEmotions Research Institute, where
scientists concentrate on uncovering the scientific basis of linkages
between emotions and health. One third of all patients treated with
antidepressants do not respond to them, and of those that do, only about 50
percent get completely better, he added.
Virtually all previous studies analyzing brain activity in depressed
people used PET (positron emission tomography) and SPECT (single photon
emission computed tomography) technology. With these imaging systems
scientists were not able to obtain pictures with the same resolution as that
which is now obtainable with fMRI, which provides a "working snapshot" of
the brain.
The Wisconsin team used fMRI's capability to capture brain activity as it
occurred to record subjects' reactions as they viewed pictures designed to
stimulate negative and positive emotions.
"We believe that we can uncover the best indicators of treatment changes
when we present research subjects these emotion challenges," said Davidson.
"The pictures activate the individual circuits that underlie different kinds
of emotional responses."
UW emotions researchers have been using fMRIs with emotion-challenging
pictures for several years in an effort to understand normal and abnormal
brain responses to a range of emotions. They theorize that in depressed
people, reactions to negative emotions are similar to, but more exaggerated
than, reactions that non-depressed people have, and that the reactions may
be more difficult to turn off.
"We all experience some sadness from time to time, but in depression, the
responses may be sustained and out of context," said psychiatrist Kalin.
With the HealthEmotions Research Institute, the Keck Laboratory for
Functional Brain Imaging and Behavior and the Laboratory for Affective
Neuroscience, UW is home to a critical mass of some of the foremost emotions
researchers in the world.
University of Wisconsin-Madison
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