Study suggests new target for PTSD treatment

Jenni Blackford, PhD

A team led by Jenni Blackford, PhD, director of the research UNMC’s Munroe-Meyer Institute, has shed light on a new aspect of post-traumatic stress disorder (PTSD).

In a recently published paper, Dr. Blackford and her team, including first author Brandee Feola, PhD, of Vanderbilt University Medical Center, explored the effects a small brain region brain – the bed nucleus of the stria terminalis (BNST) – might have on people suffering from PTSD.

Dr. Blackford, who also is a professor in the UNMC Department of Neurological Sciences, agrees that the amygdala and brain regions connected to the amygdala drive fear responses and are the one important cause of PTSD. But the study found that the BNST, located deep in the middle of the brain, also has an effect.

Studies in animals have shown that the amygdala, the paper’s authors said, provides fear responses to predictable threats, while the BNST provides anxiety responses to potential, unpredictable threats. However, because the BNST is such a tiny brain region, previous studies weren’t able to study it in humans. Dr. Blackford and her team pioneered the methods to study the BNST in humans which laid the foundation for this study in people with PTSD.

“We are really interested in these results, because most treatments don’t work well for people with PTSD — and the existing treatments target this fear network,” Dr. Blackford said.

Study participants included 32 combat-exposed veterans with PTSD and 13 combat-exposed controls without PTSD. Across all conditions, veterans with PTSD had heightened BNST activation and displayed stronger BNST and amygdala connectivity with multiple fear and anxiety regions involved in both fear stress and responses to unpredictable threat relative to controls.

“We found the amygdala is involved – similar to many other studies – but we also showed that BNST also is involved, and that people with PTSD – especially combat veterans – have differences in both of these networks,” she said. “Their fear system is on hyperdrive and now we have discovered that their anxiety system is also on hyperdrive.”

The study results, Dr. Blackford said, may provide a new treatment target for individuals with PTSD.

“One thing that these study findings tells us is that this might be why PTSD is so hard to treat,” she said. “We have some gold standard treatments, and we should keep using those, but we really need to look for treatments that can help reduce the BNST hyperactivity.”

Interestingly, Dr. Blackford said, one drug that is shown to reduce BNST activation is alcohol.  “This finding might explain why alcohol is often used by people with PTSD,” she said. “However, it is important to note that using alcohol to self-medicate PTSD symptoms is not a safe approach and also can make PTSD symptoms worse in the long run.”

Also, Dr. Blackford, who did the bulk of the research while working at the Tennessee Valley Veterans Administration Healthcare System before taking on her role at MMI, hopes other researchers build on the study’s results.

“These results give us an exciting new target for treatment,” she said. “The fact that both the fear and anxiety systems are altered in PTSD might explain why PTSD is so hard to treat. We need to find behavioral treatments or other safe medications that target both the amygdala and PTSD. People with PTSD likely need a dual approach that addresses both of these brain systems.”