Photo of John Schmidt "I'd be with a group and I could not get in the elevator with them; I'd make up a reason to take the stairs. It got pretty embarrassing."
— John Schmidt, engineer.

In the 1980s, John Schmidt fearlessly climbed on the San Francisco Bay Bridge and even helped repair it after the Loma Prieta earthquake. Yet getting into an elevator petrified the electrical engineer.

"I'd be with a group and I could not get in the elevator with them; I'd make up a reason to take the stairs," he recalls. "It got pretty embarrassing."

Schmidt couldn't do many of the things most people did everyday. He was often so afraid of dying that he had trouble sleeping at night and couldn't board an airplane. He sometimes became so dizzy that he collapsed at the office and was rushed to the hospital.

Many doctors and myriad medical tests failed to detect anything wrong with Schmidt, now 52 years old. He began to suspect he had some kind of anxiety disorder.

A clinical trial

So when he saw an advertisement in the Sacramento Bee calling for participants in a UC Davis Health System research study on panic disorder, he decided to respond.

"I was hoping to get at the bottom of this problem of mine," he explains.

Likewise, Richard Maddock, the psychiatry professor running the study, was eager to get at the bottom of panic disorder.

It afflicts one to two percent of the population.

Characterized by "out of the blue" attacks of overwhelming psychological fear, panic disorder causes physical symptoms as well: nausea, sweating, dizziness, shortness of breath and heart palpitations. While these harrowing events involve the brain's fear circuits, the root problem appears to lie much deeper – in the primitive brain stem, which sends the body into red alert when it detects suffocation or severe metabolic disturbances.

People with panic disorder experience "false alarms." So, what's triggering them? Maddock focused on one clue: these patients produce in their brains excessive amounts of lactic acid, the chemical generated when sugar is burned for energy in muscles during exercise and also in the brain during mental tasks.

Metabolic or hypoxic

Researchers have two possible explanations for this. One, called the hypoxia hypothesis, says that the excess lactic acid is caused by a transient shortage of oxygen, due perhaps to the constriction of blood vessels in the brain. A second, called the metabolic hypothesis, says that the excess lactic acid is caused by an underlying defect in an individual's metabolism.

To test these two hypotheses, Maddock designed an experiment to take advantage of magnetic resonance spectroscopy, a highly sensitive imaging tool for measuring lactic acid levels in the brain minute-by-minute. He recruited 15 untreated panic disorder patients – including Schmidt, who was finally diagnosed with the disorder – and 15 age- and gender-matched healthy volunteers.

While monitoring each subject's brain lactic acid levels, Maddock asked him or her to view a spinning checkerboard, which stimulates the visual cortex and causes a rush of blood and oxygen to that region. He expected to see a rise in lactic acid in all of the subjects. But if the hypoxia model was correct, there should be similar increases in both groups (because oxygen would be plentiful). If the metabolic model was correct, the lactic acid increase should be greater in the subjects with panic disorder. "We didn't know what to expect – frankly, we wanted to see what would happen," Maddock recalls.

The results clearly supported the metabolic model. "What we saw was that even in healthy people, the lactic acid levels in the visual cortex went up when they viewed the checkerboards," he says. "And in the panic disorder patients, it was a bigger and longer-lasting increase."

Further studies

The study ruled out the hypoxia model, suggesting that people with panic disorder have an abnormality in how they produce or clear lactic acid in the brain. Maddock presented his findings earlier this year at the annual meeting of the Society of Biological Psychiatry.

Maddock is now repeating the experiment on panic disorder patients who have been free of symptoms for a while. He's testing whether the metabolic abnormality is "a vulnerability lying under the surface that will always be there, ready to erupt."

Indeed, the disorder appears to have a strong genetic component. A fraternal twin of a panic disorder patient has a 20 percent chance of also suffering panic attacks; an identical twin – who has all the same genes – has a risk of nearly 50 percent.

"If metabolic abnormalities do turn out to be crucial, the hope is that we could start to look for the genes involved," Maddock explains. "And if we find the genes, that could lead us to novel interventions."

Schmidt, for one, views panic disorder as something he will have to manage the rest of his life. The good news is that once he received medication and behavioral therapy, he could finally again use elevators and fly on airplanes.

Now he's off the drugs and hasn't had a panic attack for a year. Looking back on the decades when he didn't know what was wrong, he says, "I've gone down a rough road; it took me a long time to realize that what was going on in my mind could affect my body."

Hoping to participate in Maddock's continuing studies, Schmidt adds, "If others might learn something from these studies that would help them, that would be a great thing."