Fort Worth Medical Student’s Research Examines New Medical Treatment for Depression

FORT WORTH – TCU School of Medicine student Ben Jacobs contributed to a new study exploring a medical treatment to help people better manage anxiety, depression and Post Traumatic Stress Disorder (PTSD).

The study was published in Biological Psychiatry A Journal of Psychiatric Neuroscience and Therapeutics in late January.

“The whole goal of the research is to understand the pathways by which anxiety and depression work,” Jacobs said. “We have gathered more information on the molecular pathway in the brain that anxiety and depression may work through. The next step would be to develop a medication that targets this pathway.”

That molecular pathway in the human brain that controls mood disorders when people experience depression, fear/anxiety and PTSD is referred to as the Orexin pathway by scientists. So far, researchers have not been able to effectively treat the pathway with current anxiety and depression drugs on the market.

“The other drawback is that most anxiety and depression drugs on the market today are highly addictive,” Jacobs said.

Currently only sertraline (Zoloft) and paroxetine (Paxil) are approved by the Food and Drug Administration (FDA) for PTSD, according to the American Psychiatric Association. Jacobs and the research team were able to find a pathway similar to the Orexin pathway in the brains of mice. They pinpointed a medication called SB-674042 that reduces the activity of the Orexin 1 receptor in the brain of mice.

“The more medication we gave the mice would result in less activity in the Orexin 1 receptor which means the mice would have less stress, anxiety and depression,” Jacobs said.

To see if the medication would help a mouse experience less anxiety when put into a stressful situation with another mouse, they constructed a brand-new test simulation box called Stress Alternative Model (SAM).  SAM, requires a box with holes on either side of the box that have a narrow diameter. A smaller test mouse is put inside the box with a larger mouse, but the holes in the box are only large enough for the small mouse to exit.

The “escape or stay” test was implemented over the course of four days with the several pairs of mice in separate boxes.

During the first two days the smaller mice were placed inside a box with larger mice without receiving any of the SB-674042 medication.

“The first two days the small test mouse had a decision to make,” Jacobs said. “Stay with the aggressive large mouse and get beat up or leave through one of the holes. The smaller mouse was much more likely to stay the first two days.”

On days three and four, they administered the medication to see if the smaller mice would reverse their decision to stay and escape out of the box.

The study revealed that once the smaller mice were given the medication on the third day, they were 30% more likely to escape the box when compared to days one and two. By the fourth day, the mice were 70% more likely to escape the box rather than stay.

“When humans experience stress, anxiety or PTSD from something like an abusive relationship they may know they should leave but don’t leave because they have too much anxiety or are to depressed to try to escape,” Jacobs said. “This medication gave those anxious and depressed mice the boost they needed to realize they have the will to live and helped them escape.”

The next step is to have other scientists and researchers from other universities throughout the world to repeat the study to see if they get the same results.

“If everyone gets the same results then ultimately the next step is to create a human clinical trial study,” Jacobs said.