Published by the Students of Johns Hopkins since 1896
May 26, 2024

Depression found to have roots in genetics

By TONY WU | February 21, 2013

Depression may sound like it is completely emotional, but some types are  actually linked to physical changes in the brain after traumatic events. While emotional causes can only be cured through therapy, there is a new discovery that shows promise in alleviating depression in people whose brains are physically affected.

Hongjun Song, a neurology professor and Stem Cell Program director at Hopkins, explored the relationship between various antidepressant drugs and a specific targeted protein.

“[Under current treatments], depression patients need to take antidepressant over long period of time to have beneficial effect and some are not responsive to current antidepressant treatment,” Song said.

Therefore, it is crucial to understand the way the antidepressant drugs work to improve their effectiveness. Song states that past studies have already shown that antidepressant drugs act by promoting neural stem cell activation. However, the underlying molecular mechanism is not well understood.

In studies involving both humans and mice, Song found that the therapies and drugs commonly used to combat depression seem to alter the amount of a specific protein present in the brain. The protein ­— sFRP3 — blocks neuronal development, essentially halting the stimulation of neural stem cells. The amount of sFRP3 is found to be crucial in the treatment of depression patients.

In previous experiments, an elevated amount of sFRP3 appeared to be a major cause of depression in patients. By reducing stimulation to neural stem cells, sFRP3 prohibits the creation of new neurologic pathways, which eventually causes depression.

“Previous studies have shown that antidepressant treatments in animal models promote neural stem cell activation, which in turn is required for antidepressant responses in certain animal models,” Song said.

In the studies, the research team led by Song compared mice which were genetically engineered to operate without sFRP3 proteins and normal mice which were given antidepressant drugs. The comparison yielded interesting results. They found that the behaviors of the mice without sFRP3 are similar to those of the mice on antidepressant drugs. Furthermore, the actions of the sFRP3-free mice did not alter significantly when given antidepressant drugs.

After conducting initial experiments on mice, the researchers decided to apply their new research ideas to the human brain. In order to find the link between the effectiveness of antidepressant drugs and sFRP3 in human brains, the team analyzed the genes of patients suffering from depression. More than 500 sets of genetic information were processed and the result corroborates the findings in mice experiments.

The researchers noticed that sFRP3 in humans play the same role as those in mice. In addition, there are three variations of the gene that demonstrates better response to therapy. The team states that the three variations have better responses because they undergo less gene activity. Less gene activity indicates a decreased production of the protein itself, which leads to a lower extent of neural inhibition.

However, in the study of humans, the researchers also discovered a few complicating variables that could not be overlooked. The level of sFRP3 is not entirely dependent on genetics. Other factors such as exercise also have an effect on the amount of sFRP3 present in the brain.

The correlation between genes and depression is an astonishing discovery. By linking the genetics of depression patients to the production of the specific protein, sFRP3, the studies suggests that it is possible to ascertain the risk of depression in humans through genetic analysis. By obtaining a genetic mapping of the person, healthcare providers will be able to determine the risk of the individual acquiring depression.

Furthermore, the discovery that depression is linked to a protein produced by the body also shows promise in the development of new drugs.  All these implications reveal a promising future in the field of antidepressant drugs and therapies.

“Understanding the underlying mechanism may lead to development of more effective antidepressant treatments with little or no side effects,” Song said.

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