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
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 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 dont 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
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
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