Common SSRI antidepressants change brain structure in non-depressed users

Commonly prescribed antidepressants—such as Zoloft® (sertraline) and other selective serotonin reuptake inhibitors (SSRIs)—may alter brain structures differently in depressed people than in non-depressed people, according to a study published online June 24, 2015 in Neuropharmacology.

In a study conducted in primates with brain structures and functions similar to those in humans, researchers found that sertraline significantly increased the volume the anterior cingulate cortex in depressed subjects but decreased the volume of the anterior cingulate cortex and the hippocampus 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 lead author of the study Carol A. Shively, PhD, professor of pathology-comparative medicine at Wake Forest Baptist Medical Center, in Winston-Salem, NC.

In humans, smaller volumes of the cingulate cortex and the hippocampus have been found in depressed people compared with non-depressed individuals, Dr. Shively said. Antidepressant drugs like sertraline can promote neuron growth and connectivity in these brain regions.

But SSRIs, including sertraline, are also prescribed for many disorders besides depression, including bulimia, hot flashes, obsessive-compulsive disorder, post-traumatic stress disorder, stroke recovery, and sexual dysfunction. There are no studies on the effects of these drugs on brain volumes in individuals not diagnosed with depression. This research aimed to explore these differences.

In the study, researchers fed 41 middle-aged female cynomolgus monkeys a diet formulated to replicate that consumed by many Americans for 18 months, during which time the researchers recorded depressive behavior in the animals. (Middle-aged female monkeys were chosen for this study because depression is nearly twice as common in women as in men and the use of antidepressants is most common in women ages 40 to 59.)

After the initial 18-month period, the monkeys were randomized 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 the other 20 monkeys received a placebo. This treatment regimen is analogous to a human taking an antidepressant for approximately 5 years.

The researchers found that the SSRI reduced anxiety in the monkeys, but did not affect depression.

At the end of the treatment phase, the researchers took MRI images, which revealed that the drug significantly increased the volume of the anterior cingulate cortex in depressed subjects, while decreasing the volume of this same region and the hippocampus in non-depressed subjects. Both of these areas are implicated in major depressive disorder and are highly interconnected with other areas of the brain. They are also critical in a wide array of functions including memory, learning, spatial navigation, will, motivation, and emotion.

“The study’s findings regarding the different effects of sertraline on brain-region volumes in depressed versus non-depressed subjects are compelling,” Dr. 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.”

For more information on depression, please visit the Depression Resource Center on MDLinx.