A study performed using non-human primates (with similar brain structures and functions as humans) revealed that the antidepressant sertraline – a selective serotonin reuptake inhibitor (SSRI) – commonly manufactured as Zoloft, significantly and disproportionately increases brain volume in depressed individuals. Moreover, the medicine was seen to decrease the volume of two brain regions in non-depressed participants.

Using Primates To Check The Effects Of Sertraline

Zoloft is a very common and widely prescribed medicine for various psychological disorders, commented lead author Carol A. Shively, Ph.D., Professor of Pathology-comparative Medicine at Wake Forest Baptist. Hence, the observations made in this study are of primal value.

Researchers fed 41 middle-aged female monkeys a specifically formulated diet that replicated what most Americans ate daily. The monkeys were fed the diet for 18 months, during which depressive behavioral change were recorded. Only female monkeys were chosen for the study since depression is almost twice as common in females as in males, and antidepressants are mostly used by women between the ages of 40 and 59.

After the 18-month pre-study, the monkeys were assigned to two groups balanced for BMI, body weight and depressive behavior. Then, for another 18 months, 21 monkeys were daily given sertraline in doses comparable to those given to humans, and the other 20 monkeys were given a placebo. This treatment regime is similar to a human taking sertraline for almost five years.

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Images taken at the end of treatment, via MRI, revealed that depressed subjects taking the drug had significantly increased volumes of the anterior cingulate cortex. However, the volumes of this region, along with the hippocampus, were significantly decreased in non-depressed monkeys. Both these regions of the brain are highly interconnected with other areas, and are involved in various functions such as learning and memory, spatial navigation, will and motivation, and emotion – all highly susceptible in major depressive disorder.

Dr Shively said that volume differences in neural structures have been observed in non-depressed and depressed individuals, and the most common differences are reported in the regions seen in their study. This implies that a possible mechanism of action of antidepressants is promoting connectivity via the growth of neurons.

Future Prospects

Selective serotonin reuptake inhibitors (SSRIs), such as zoloft, are commonly prescribed for disorders other than depression as well, such as bulimia, obsessive-compulsive disorder (OCD), hot flashes, post-traumatic stress disorder (PTSD), recovery from stroke and sexual dysfunction. To date, there was no data predicting the effect of these medicines on brain volumes of non-depressed people.

“The study’s findings concerning the divergent effects of sertraline on specific brain-region volumes in depressed and non-depressed subjects are compelling”, concluded Dr Shively in the study published in Neuropharmacology. “However, given the various disorders for which SSRIs are prescribed, further research needs to be conducted in patient populations to assess if these drugs produce similar effects in humans”.