Research looks at how the Tob gene is connected to depression, fear, and anxiety

A new study has revealed that the gene, Tob, supports stress-resilience and plays a significant role in reducing depression, fear, and anxiety.

The research, published in the journal, Translational Psychiatry, was conducted by scientists at Okinawa Institute of Science and Technology (OIST) Graduate University in Okinawa, Japan.

Expanding on previous research by Tadashi Yamamoto, BSc, PhD, a professor at Osaku University, that demonstrated that the gene, Tob, is well known for the role it plays in cancer and regulating the cell cycle and body’s immune response, this study found the gene is also instrumental in reducing depression, fear, and anxiety.   

“This research is about understanding stress-resilience,” said Mohieldin Youssef, PhD, a former student of Yamamoto, and the study’s lead author in a statement. “The presence of the gene helps with stress-resilience and if it’s removed, there’s an increase in depression, fear, and anxiety.”

According to Youseff, Tob is named for the Japanese verb “tobu”, which means to fly or to jump. This is because when the cell is exposed to a stimulus, its protein levels jump in activity. He said that this has resulted in the gene being classed as an immediate-early gene, as it has such a fast response. 

“The Tob gene is related to many different phenomena but working on the brain system is particularly challenging,” Yamamoto said in a statement. “Although it was previously suspected, this research is the first work that clarifies that Tob has a function in the brain against stress.”

The researchers came to the conclusion that the Tob gene is linked to anxiety, fear, and depression by conducting several different experiments. According to the study, when mice were first exposed to stress, they witnessed the Tob protein levels increase. Then they evaluated mice that had been born without a Tob gene and found and uptick in depression, fear, and anxiety.

In addition, through an MRI, they found that the connectivity between two key places regulating the brain’s stress resilience was altered when the Tob gene was removed—the hippocampus and the pre-frontal cortex. From there, the researchers decided to look at the specific role that the gene plays within the hippocampus.

“We’ve concluded that the Tob gene within the hippocampus suppresses fear and depression,” said Youssef. “But the suppression of anxiety must be regulated by another part of the brain. Uncovering this role of the Tob gene in fear, depression, and anxiety could have vast implications for developing therapeutics for psychiatric stress.”