A single dose of a selective
serotonin reuptake inhibitor (SSRI) dramatically and rapidly alters functional
connectivity throughout the brain, a new study shows.
Functional magnetic resonance
imaging scans of the brains of healthy adults before and after a dose of
escitalopram (Lexapro, Forest Laboratories, Inc) revealed changes in
connectivity within 3 hours, the study team says.
"We were not expecting the
SSRI to have such a prominent effect on such a short timescale or for the
resulting signal to encompass the entire brain," Julia Sacher, MD, PhD, of
the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany,
commented in a news release.
The study was published online September
18 in Current Biology.
Serotonin is an essential
neuromodulator involved in mood regulation. SSRIs are among the most widely
studied and prescribed classes of antidepressants, yet it is still not
completely clear how they work. They are thought to alter brain connectivity in
specific pathways, but those effects had generally been thought to take place
during a period of weeks, not hours, the investigators note.
The new findings suggest that
changes begin to take place right away and throughout the whole brain.
Dr. Sacher and colleagues
measured changes in
connectivity in 22 antidepressant-naive and medication-free healthy men and
women in their mid-20s in a randomized, double-blind, placebo- controlled
functional magnetic resonance imaging (rs-fMRI) sessions: after a baseline
scan, they received either a single oral dose of escitalopram (20 mg) or
placebo. Serum levels of escitalopram were determined after 3 hours, after
which the participants underwent a second rs-fMRI scan. After an 8-week washout
period, the protocol was repeated with the alternate drug.
The researchers found that
a single 20-mg dose
of escitalopram sparked a widespread decrease in connectivity in most cortical
and subcortical areas, with the exception of localized increases in
connectivity in cerebellar and thalamic regions.
The findings, say the researchers,
"challenge the view that SSRI-induced changes are limited to decreases in
connectivity. These findings provide evidence for the particular relevance of
serotonin for the modulation of intrinsic brain activity and also demonstrate
its unique influence on the cerebello-thalamic tract."
The researchers say their
findings represent an essential first step toward clinical studies in patients
with depression. They plan to compare functional connectivity patterns of
brains in recovery and those of patients who fail to respond to SSRI treatment.
Understanding the differences
between the brains of individuals who respond to SSRIs and those who do not
"could help to better predict who will benefit from this kind of
antidepressant vs some other form of therapy," Dr. Sacher said in a news
"The hope that we have is
that ultimately our work will help to guide better treatment decisions and
tailor individualized therapy for patients suffering from depression," she
The study was supported by the
Society in Science–The Branco Weiss Fellowship. The authors have disclosed no
relevant financial relationships