commonly prescribed antidepressant may alter brain structures in depressed and non-depressed
individuals in very different ways, according to new research at Wake Forest
Baptist Medical Center.
study – conducted in nonhuman primates with brain structures and functions
similar to those of humans – found that the antidepressant sertraline, a
selective serotonin reuptake inhibitor (SSRI) marketed as Zoloft, significantly
increased the volume of one brain region in depressed subjects but decreased
the volume of two brain areas in non-depressed subjects.
“These observations are important for human
health because Zoloft is widely prescribed for a number of disorders other than
depression,” said Carol A. Shively, Ph.D., professor of pathology-comparative medicine
at Wake Forest Baptist and lead author of the study, published in the current
online issue of the journal Neuropharmacology.
the study, 41 middle-aged female monkeys were fed a diet formulated to
replicate that consumed by many Americans for 18 months, during which time
depressive behavior in the animals was recorded. Female monkeys were chosen for
this study because depression is nearly twice as common in women as men and the
use of antidepressants is most common in women ages 40 to 59.
the 18-month pre-study phase, the monkeys were divided into two groups balanced
for body weight, body mass index and depressive behavior. For the next 18
months, 21 monkeys received sertraline in daily doses comparable to those taken
by humans while a group of 20 received a placebo. This treatment regimen is
analogous to a human taking an antidepressant for approximately five years.
images taken at the end of the treatment phase revealed that in depressed
subjects the drug significantly increased the volume of one region of the
brain, the anterior cingulate cortex, while decreasing the volume of this same
region and the hippocampus in non-depressed subjects. Both of these areas are
highly interconnected with other areas of the brain; are critical in a wide
array of functions including memory, learning, spatial navigation, will,
motivation and emotion; and are implicated in major depressive disorder.
humans, Shively said, volume differences in neural structures have been noted
in depressed and non-depressed individuals, with the most commonly reported
differences being smaller volumes of the cingulate cortex and hippocampus in
depressed people. One potential mechanism through which drugs such as Zoloft
can be effective as antidepressants is by promoting neuron growth and
connectivity in these brain regions.
SSRIs, including Zoloft, are prescribed for a variety of disorders besides
depression, including bulimia, hot flashes, obsessive-compulsive disorder,
post-traumatic stress disorder, stroke recovery and sexual dysfunction, and
there are no studies of the effects of these drugs on brain volumes in
individuals not diagnosed with depression.
study’s findings regarding the different effects of sertraline on brain-region
volumes in depressed versus non-depressed subjects are compelling,” Shively
said. “But given the number of different disorders for which SSRIs are
prescribed, the findings need to be investigated further in patient populations
to see if these drugs produce similar effects in humans.”
study was funded in part by National Institutes of Health grant HL078103.
of the study are J. Daniel Bourland, Ph.D., Ashlee Clark, M.S., James B.
Daunais, Ph.D., Warwick D. Johnston, B.A., Sara R. Jones, Ph.D., Robert A.
Kraft, Ph.D., Adreanna Massey, B.A., David Neely, B.S., Beth Uberseder, B.S., and
Jeff D. Williamson, M.D., of Wake Forest Baptist and Stephanie L. Willard,
Ph.D., of the University of Pennsylvania.