New Research Hopes to Rid Brain of Anxiety

March 25, 2010— -- Getting on an airplane, lying still in an MRI machine or even public speaking can paralyze Helen Resneck-Sannes' patients, whose arousal systems are in full-fear mode.

"They take beta blockers or valium and it really doesn't stop the fear," the Santa Cruz, Calif., psychologist said. "The next time they are on the airplane or speaking or claustrophobic, they are still afraid."

Drugs to treat those who suffer from phobias and anxiety disorders have been used for decades with some success, but there is still no medical silver bullet for those who are irrationally afraid or traumatized.

Just this week, scientists at the University of Hiroshima in Japan found a way to switch off the fear center in the brain by injecting a shot of lidocaine, an anesthetic, to the brain -- of goldfish, that is.

The brains of goldfish share many similarities with those of mammals, including humans, according to researchers, who hope to understand more about biological and chemical processes that cause humans to be afraid.

"I think it would be great if someone needs to get an MRI if you could give them a shot of lidocaine," said Resneck, who wrote the 2002 book, "There Really Is Something to Be Afraid Of: Treatment of Panic Disorder."

"On the other hand, if you can find out the reasons for the claustrophobia, it would be better," she said. "But in an emergency, that would be a really good idea."

Fear is the most primal of all emotions, the lynchpin of the "fight or flight" response that protects human beings against danger. But in about 40 million Americans, that mechanism is out of control.

Anxiety disorders are the most common mental illness in the United States, affecting about 18 percent of the population, according to the Anxiety Disorders Association of America (ADAA).

Only about one third of those who are suffering receive treatment, which is usually a combination of drugs and behavioral therapies. They are three to five times more likely to go to the doctor and six times more likely to be hospitalized for psychiatric disorders than those who do not suffer from anxiety disorders, according to the ADAA.

Anxiety disorders develop from a complex set of risk factors, including genetics, brain chemistry, personality and life events.

Shocking Goldfish to Create Fear

In the Japanese experiment, researchers taught goldfish to become afraid of a flashing light. Each time the light was switched on, the fish received a low-voltage electric shock.

The fish learned to associate the light with the pain and soon, they became afraid of the light, even without the shock. Scientists noticed that their heartbeats sped up, similar to how humans react when they are afraid.

But when scientists injected lidocaine into the cerebellum part of the brain an hour before the experiment began, the fish showed no symptoms of fear when the light was shone.

Lidocaine is similar to Novocain, which is used by dentists to numb teeth.

Once the lidocaine wore off, however, the fish experienced fear again.

"Chronic anxiety is a huge problem and some of it is perfectly justified, if we are worried about safety or finances," said Bruce McEwen, a neuroscientist at Rockefeller University in New York City.

"The purpose of fear is to alert us to danger and to create memories that allow us to remember," he said. "But abnormal fear and anxiety, we don't like or want that."

In humans, doctors prescribe tranquilizers to treat a variety of anxiety disorders, which work much the same way as the lidocaine in goldfish, McEwen said.

"They have the classic calming down effect," he said. "But why would you want to suppress fear in the first place. It's fear that prevents us from doing crazy things. One can argue that psychopaths don't have fear of consequences."

Drugs like benzodiazepines can be addictive and hard to "wean off," McEwen said.

Antidepressants and atypical neuroleptic agents have also been used to treat anxiety disorders, but they, too, have side effects. These drugs can cause agitation and withdrawal symptoms.

"There are no easy solutions," he said. "The message is we would not always want to give a pill because often these systems are involved in doing good things."

Scientists have only tapped the "tip of the iceberg" when it comes to understanding these disorders, according to McEwen, but they do suspect a combination of genetic factors and life experiences.

"Good science has been done on how important the environment is," he said. "Adverse events in childhood can have terribly adverse consequences."

Parents can sometimes transmit those anxieties to their children.

"The spookiest part is that studies of Holocaust survivors showed the children had the same symptoms as their parents," McEwen said. "How is that passed on?"

Shocking Goldfish to Create Fear

Therapist Resneck-Sannes uses behavioral therapy to help her patients through their most frightening phobias.

"One woman is terrified of the MRI, even the open one, so I started to go through her history and get some understanding of how it happened and started looking at her defensive responses," she said.

Resneck-Sannes said she is teaching the woman to slow her breathing and heart rate and to imagine scenarios when she is not angst-ridden.

"There is an arousal system in the body and what the body wants to do is escape," she said. "It depends on the disorder, but we use a combination of thinking thoughts and calming the arousal in the body so they can feel like they have some control."

But new research on rats and humans may open even more doors to helping those with fears.

Elizabeth Phelps, a professor of psychology at New York University, questioned whether the Japanese goldfish research would have any applicability to humans, whose fear center is based in the amygdala in the temporal lobe, not the cerebellum, where it is in the fish.

She has been doing pionering research on the amygdala , a region of the brain located deep within the medial temporal lobes, a part of the limbic system that controls emotions.

NYU scientists have already discovered that they can inject drugs into the amygdalas of rats to prevent re-storage of memories and effectively erase them.

Such interventions are not safe in humans, say researchers, but they have learned much about how new brain memories are stored.

"These brain regions are important in the expression of that memory," Phelps said. "It's not what you tell me you remember. Memory is more than that. It's how to ride a bike or the anxiety when you encounter something that was dangerous before. It's a big component of what is so traumatic, the pathological aspect of memory."

Phelps and her colleagues have found non-invasive techniques to rewrite emotional memories that trigger fear during the storing of those memories -- a process known as reconsolidation, as new neural connections are made.

When psychologists use behavioral exposure therapy to rid patients of fears, they are merely creating a new memory that competes with the old one, according to Phelps.

"One overrides the other," she said. "But the big problem is that the first memory is still there," she said. "You get stressed and the fear comes back, like smoking -- quitting and starting up again."

By exposing a person to a bad memory at exactly the right time, the information associated with a painful memory can be rewritten, a process that could have huge implications in the treatment of post-traumatic stress disorder.

"We don't know if this can extend to complicated situations like phobias," Phelps said.

But if a patient can undergo exposure therapy during just the time window when memory is being restored, negative memories can be rewired to positive ones.

Said Phelps, "It's all about timing."