Easier for Him to Say

The mouth disconnects from the brain. You start to speak and nothing comes out. At the drive-thru window, you order the food you can pronounce, not the food you want. You fret over making a presentation to colleagues because the simple act of speaking is a struggle.

Gerald Maguire knows the frustrations well. He is a stutterer.

That is why the UC Irvine psychiatry professor is trying to find a cure for the disorder, which affects 3 million Americans. When he says a new drug shows promise, he knows what he’s talking about. Not only did he devise the experiment to test its effectiveness, he takes the pill every evening.

Even if he spoke without difficulty, Maguire would be unusual. Most scientists researching the disorder are speech pathologists. Maguire is one of a handful of physicians, and maybe the only psychiatrist, studying the causes of stuttering.

“I was always fascinated with how the brain works,” Maguire said. “I wanted to know how my brain works, why sometimes I was fluent and sometimes I was disfluent.”

Maguire’s work is helping transform the way stuttering is viewed and treated. Long regarded as an educational or psychological problem, stuttering increasingly is seen as a medical disorder rooted, at least in part, in the chemistry of the brain.

Maguire, 36, has been a pioneer in searching the brain for the sources of stuttering and in using drugs to control the disorder. He performed the first brain scans on stutterers. They showed that when levels of the chemical dopamine were reduced through drug therapy, activity in a deep portion of the brain increased and stuttering decreased.

Now, Maguire is trying to identify medicine that will offer the biggest improvement in fluency with the fewest side effects.

His work is receiving enthusiastic notice in the field.

“It’s exciting because it suggests there may be a way to pharmaceutically manipulate what’s going on,” said Ben Watson, a professor of speech physiology at New York Medical College. Maguire’s research, he said, holds out hope of significantly easing stuttering “by changing the underlying brain chemistry.”

Maguire’s stutter is barely noticeable these days, an improvement he credits to olanzapine, an antipsychotic drug with which he is experimenting. He gets stuck on some words--repeating the p in pilot, for instance--and sometimes elongates words.

But he’s come a long way from the days when he struggled to say his name and avoided the telephone. As a psychiatric resident at UC Irvine Medical Center in Orange, Maguire would run to the nurse’s station when he was paged rather than respond by phone.

“They thought this resident was so attentive,” he said with a laugh.

For most of his life, every time Maguire opened his mouth, he worried what would come out.

Many of the 1% of Americans who stutter suffer the same fears. Their fractured speech often is attributed to stupidity or nervousness. Not only do they struggle to speak, but the accompanying tics, grimaces and contortions offer ammunition for tormentors and add to the discomfort of friends and acquaintances.

“My experience has been that people are not deliberately rude to people who stutter,” said Granville Kirkup, an Irvine entrepreneur who has participated in Maguire’s drug experiments. “They just don’t understand it, and that makes them uncomfortable.”

Kirkup, an executive vice president and founder of Telmar Network Technology, a provider of telecommunications equipment and services, has donated $250,000 to UC Irvine for Maguire’s research. Eli Lilly & Co., the maker of olanzapine, has contributed $60,000.

At 36, married and the father of a 2-year-old daughter, Maguire still gets teased. He’ll stumble while ordering a cheeseburger, and the waitress may mimic him. Or he’ll trip over “Maguire.” “Oh, you forgot your name?” he’ll be asked.

He shrugs off the slights. “Sometimes I tell them, ‘No, I stutter.’ I try to educate them. I don’t want the next person to go through it.”

Science has long struggled to identify the cause of stuttering. Through the years, some researchers thought it was behavior learned from parents, siblings or playmates. Others thought the cause was psychological, stemming from an abnormally close relationship between mother and child. Still others said stuttering stemmed from anxiety.

The American Psychiatric Assn. classifies stuttering as a psychiatric problem, which puts it in the same category as bipolar disorder and severe depression. Maguire once read that it was caused by “unresolved pregenital oral sadistic conflicts.”

“I’m a board-certified psychiatrist, and I don’t know what that means,” he said.

These days, however, researchers theorize that stuttering springs from multiple causes, ranging from brain chemistry to heredity to environmental factors.

People nearly always begin stuttering between the ages of 2 and 4. About 60% of children outgrow it by puberty, suggesting an association with brain development.

The disorder affects four times as many males as females. Studies show that identical twins both stutter in 63% of cases, whereas among fraternal twins, both children stutter only 19% of the time--an indication that heredity plays a role. Stuttering appears to be passed more often through the mother.

Actor James Earl Jones, singers Mel Tillis and Carly Simon, and basketball star turned broadcaster Bill Walton have battled the disorder. Former Raiders defensive back Lester Hayes stuttered so badly during a nationally televised interview after the 1983 Super Bowl that he was incomprehensible.

Scholars say a biblical quotation attributed to Moses: “. . . I am slow of speech and of a slow tongue,” suggests he too was afflicted.

One mystery of stuttering is that it disappears when a person affects an accent, sings or otherwise changes his voice. It sometimes ceases when a person reads aloud with others. Maguire believes that in these circumstances, the speaker somehow bypasses the brain mechanism that causes stuttering.

Maguire seems not the least bit self-conscious about his stuttering. If he were, he said, he would have taken up a specialty like radiology, where talking with patients would be minimal.

“Maybe unconsciously I was hopeful that stuttering would be more accepted in psychiatry than other fields,” he said. “I know in psychiatry you have a longer-term relationship [with patients]. Most first impressions with stutterers are not good.”

Stuttering may even help him develop rapport with his patients, Maguire said. He recalled one who told him: “I think you’ll understand me. I’ve struggled with depression my whole life, and I think you’ve struggled with something your whole life.”

“She didn’t say stutter,” Maguire said. “But I knew what she meant.”

Maguire grew up near the Northern California town of Chico, the youngest of four boys and a girl born to a registered nurse and a psychiatrist for the Butte County Mental Health Department.

At age 8, Maguire tried speech therapy and biofeedback, a technique that seeks to enhance a person’s control over automatic body functions. The idea was that biofeedback could help relieve anxiety, which was seen as a major factor in stuttering.

A brainy child who was driven to succeed, Maguire would look up words he had difficulty pronouncing to find synonyms he could say more easily. The speech therapist thought he was improving; his vocabulary grew.

Outwardly, he didn’t seem to be suffering, but in private he wondered why he suffered such an affliction.

“Ninety-nine out of 100 people who stutter say that,” Maguire said.

To deflect attention from his speech disorder, Maguire became the class comedian, cracking up classmates with imitations of Donald Duck, W.C. Fields, Elmer Fudd and a famous stutterer, Jimmy Stewart.

In high school, Maguire acted as if his stutter didn’t exist. After tryouts, the faculty voted him commencement speaker, and students elected him their representative to the school board. As a junior, he won a debate competition, stuttering all the way.

Maguire honed his sense of humor as an undergraduate at UC Davis. In the deadly serious world of biochemistry majors, he stood out, friends recall.

In one class, groups of students analyzed a journal article to determine if the author really had discovered a new protein. One by one, the groups presented their conclusions before the class, each more boring than the one before. Maguire’s group performed a “People’s Court” spoof called “The Protein Court.”

In medical school at St. Louis University, Maguire considered becoming a pediatrician. “Little kids, they don’t care if you stutter,” he said.

An experience in his second year helped lead him to psychiatry. Once a week for a month, he followed a pediatrician on his rounds. The pediatrician seemed to view his patients as a collection of ailing organs, not as people. By contrast, a psychiatrist that Maguire followed knew his patients by name, and without looking at their charts could delve into detail about their problems.

Maguire became interested in the science of stuttering during his second year of residency at UC Irvine, while looking for a research project. His psychiatrist father read an article about the medications that had been tried to treat the disorder. The article said doctors had some success with haloperidol, a powerful antipsychotic drug, but that the side effects were too severe to permit its use for stuttering.

“I told him that no one in field seems to know anything,” said his father, also named Gerald Maguire. “It seems there’s something here. It seems to be a natural since you’ve got the problem.”

Maguire’s first experiments tested blood-pressure medications, because some doctors had reported that as a side effect, patients who stuttered became more fluent. Maguire’s study did not find proof that the medication worked.

Maguire teamed up for the study with Glyndon Riley, a professor of communications disorders at Cal State Fullerton and one of the most respected stuttering researchers in the country. The speech and language pathologist developed the Riley Stuttering Severity Instrument, in which subjects are videotaped and the percentage of syllables stuttered, and the duration of each stuttering event, are measured.

Riley became a mentor to Maguire. As Maguire continued his research, Riley scored the subjects’ stuttering. “I was no longer an outsider in the world of stuttering, but an insider because of Glyn,” Maguire said.

In 1993, Maguire put patients under an instrument that allows researchers to see what portions of the brain are used during a specific activity. Their research found that the left caudate, located deep in the brain, was not nearly as active in stutterers as in those with normal speech. It was the first time anyone had pinpointed a part of the brain that might be responsible for stuttering.

Maguire’s theory is that stuttering is associated with an overload of dopamine in the brain. Drugs such as haloperidol weaken dopamine’s effect. Dopamine, produced in a portion of the brain called the substantia nigra, helps regulate speech, muscle motion, reasoning, behavior and emotion. Patients with Parkinson’s disease are deficient in dopamine. The chemical is found throughout the brain, but the left caudate usually is especially rich in dopamine.

In 1994, Maguire experimented with a new antipsychotic drug, risperidone, that seemed to cause fewer side effects. Caudate activity jumped in subjects put through the PET scanner, while incidents of stuttering dropped. “That was very exciting,” said Maguire, who took the drug himself.

But many patients complained of lowered libido and depression.

Maguire was running up against a problem that had bedeviled researchers a couple of decades earlier. Like him, they thought there was a dopamine connection. But the drugs they tried were so powerful that the research fell out of favor.

When the antipsychotic drug olanzapine was introduced in 1997, Maguire again became his own first guinea pig. The results were promising, so he launched a clinical trial in which he was strictly a researcher and not a subject.

Twenty-three people took part in the three-month experiment. Twelve received olanzapine in doses one-10th to one-third those used for antipsychotic treatment; 11 received placebos. Using Riley’s scale, Maguire found that olanzapine lowered incidents of stuttering by 40%, compared to 15% for the patients on the placebo. The only side effects were a slight weight gain and drowsiness.

Maguire and Riley presented their research at conferences of the American College of Neuropsychopharmacology and the American Speech and Hearing Assn. last year. They also have submitted it to the Journal of Clinical Psychiatry, where it is undergoing peer review.

Maguire receives two to three e-mails a day from stutterers inquiring about his research, from as far away as Pakistan and Indonesia.

Maguire can tell them how the drug has helped him. When he had the flu, he didn’t take olanzapine for two days and noticed how much more he stuttered. When he plans to speak before a large group, he’ll double the dose.

“I knew Jerry before he started any type of medication,” said David Franklin, research manager for UC Irvine’s psychiatry program and a co-investigator on Maguire’s studies. “It changed him quite a bit. He feels more free in speaking in public auditoriums. Now it seems those stressful times don’t affect his speech as much.”

Maguire doesn’t think drugs alone are the answer to stuttering. He envisions a combination of medicine, speech therapy and psychological counseling.

His patients look at Maguire’s own success with drugs, and it gives them hope. There is more work to be done to determine whether there is a genetic, viral or bacterial link to stuttering.

Maguire is hopeful when he considers his own work and the discovery of a connection between stuttering and dopamine.

“It’s not the total story because people don’t get 100% better,” he said. “But this may be the beginning.”