Scientist at Work | Thomas McGlashan
A Career That Has Mirrored Psychiatry's Twisting Path
By BENEDICT CAREY
Published: May 23, 2006
The patient, Keith, was a deeply religious young man, disabled by paranoia, who had secluded himself for weeks in one of the hospital's isolation rooms. In daily therapy sessions he said little but was always civil, seemingly pleased to have company and grateful for a cigarette and a light.
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ALTERED NOTIONS Dr. Thomas McGlashan
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Until one spring morning, when he wrestled the lighter from his therapist's hand and held it to his own head ? igniting his hair.
"I grabbed him and was slapping at the flames, and he immediately became passive," said Dr. Thomas H. McGlashan, the man's therapist. "He went limp and pulled a blanket over his head."
He added, "That patient, that experience, changed everything for me."
In a career that has spanned four decades, Dr. McGlashan, now 64 and a professor of psychiatry at Yale, has with grim delight extinguished some of psychiatry's grandest notions, none more ruthlessly than his own. He strived for years to master psychoanalysis, only to reject it outright after demonstrating, in a landmark 1984 study, that the treatment did not help much at all in people, like Keith, with schizophrenia. Once placed on antipsychotic medication, Keith became less paranoid and more expressive. Without it, he quickly deteriorated.
Dr. McGlashan turned to medication and biology for answers and in the 1990's embarked on a highly controversial study of antipsychotic medication to prevent psychosis in high-risk adolescents. But doctors' hopes for that experiment, too, withered under the cold eye of its lead author.
Early this month, Dr. McGlashan reported that the drugs were more likely to induce weight gain than to produce a significant, measurable benefit.
Through it all, he has remained optimistic, restless, hopeful that he is close to understanding some of schizophrenia's secrets. In a way, his work mirrors the history of psychiatry itself, its conflicts and limits, its shift away from talk therapy to drugs and biological explanations for illness.
And for those who want a sense of what direction the field will take next ? and how ? Dr. McGlashan may serve as a kind of bellwether.
"Basically, you're talking about a person who can walk into an extremely hostile environment and deliver bad news; I don't know how to describe him better than that," said Dr. Wayne Fenton of the National Institute of Mental Health. He is a former colleague of Dr. McGlashan's at Chestnut Lodge, a psychiatric hospital in Rockville, Md., closed in 2001.
"At the lodge, he stood up and, in essence, told all these giants of psychotherapy that there was not a shred of evidence that what they were doing with schizophrenia patients was helping, much less curing the disorder," Dr. Fenton said. "And the therapies were being advertised as cures."
Dr. McGlashan is recognizable from a distance, a lean figure striding across the grounds of the medical school as if against a strong wind, chin forward beneath a mop of white-gray hair. On a typical day, he visits with adult patients at a state mental hospital in the morning and with adolescents in a private institute in the afternoon. He is a deliberate presence, solemn for long periods; but then he will remark on something absurd and tip backward with laughter.
This unsettling combination ? gravity punctuated by sudden levity ? may help explain his comfort with the world of psychosis.
"I thought he was the Antichrist when I first met him; I thought all the therapists were," said Keith, the patient at Chestnut Lodge who changed Dr. McGlashan's thinking in 1982. "But in the end I liked his sense of humor, and he liked mine, and I keep in touch with him."
Keith, who is now 47 and spoke by telephone only on the condition that his last name not be used, said he set his hair on fire that day because he was terrified that a great tribulation was at hand, during which he would be dragged by his hair before the devil.
"I really believed it was coming, any moment, and there was no way to escape," he said. "I still believe it's coming, but not right now; I'm not afraid of it." Dr. McGlashan joined the staff of Chestnut Lodge at a time when psychoanalysis was in ascendance in psychiatry, nowhere more so than at the lodge, which became known for its commitment to treat severe mental illness without antidepressants, antipsychotic drugs or electroshock therapy. It was thrilling just to be there, Dr. McGlashan recalled, hearing so many accomplished therapists offer seemingly powerful ideas about what troubled patients and why.
At the time he was treating Keith, Dr. McGlashan was pursuing a study for the hospital's owner, Dr. Dexter Bullard, to track patients years after treatment. Their records were revealing artifacts, detailing thousands of interactions in which therapists, steeped in psychoanalytic theory, tried to interpret patients' every word and gesture.
In one account, a psychiatrist described an outing when he bought a patient an ice cream cone. The patient refused it vehemently. "This was very exasperating to me," the therapist wrote. "She never did accept the cone, and I had to throw it away. I thought of it at the time as having represented a kind of rape situation to her."
Yet in his analysis of 446 cases, Dr. McGlashan found that about two-thirds of the former patients with schizophrenia who had been treated with psychoanalysis were functioning poorly and struggling in their relationships and in their jobs, if they had them. Their lives were no better than those of similar patient groups who had received little psychotherapy or none at all.
"I felt like people at the lodge had become lost in the process," he said. "We would have all these erudite conversations, talking about interpretations, and meanwhile the patient is crumpled in the corner of his or her room."
Chestnut Lodge changed some of its policies as a result of the study, allowing more drug treatment, job training and other programs.
Dr. McGlashan's intensity, and willingness to reverse course, was evident even in childhood. An ardently religious boy, he grew up with two sisters near Rochester, where his father worked at Kodak. In middle school, the youngster pored through the Bible, to the dismay of his father and the bemusement of his mother.
The devotion was isolating, Dr. McGlashan remembers, creating a mostly private world of mystery and awe. Then in his first year of high school, he met other Christian students, who belonged to a group devoted to proselytizing.
He was reluctant to join, and his father sensed it. "He saved me," Dr. McGlashan said. "He picked me up after a meeting and said it was O.K. to pull back" from the group.
"He was giving me permission."
He graduated second in his high school class and studied chemistry at Yale. He then entered the University of Pennsylvania's medical school, where, during a psychiatry rotation, he met his future. He interviewed a middle-aged Philadelphia businesswoman, who described to him a tortuous plot being hatched against her, involving family members and the F.B.I. "I thought, 'She can't possible believe this,' " Dr. McGlashan said.
He was hooked. Psychosis was isolating, too, and deeply mysterious even to scientists who spent their lives thinking about it. By the 1990's, most psychiatrists believed schizophrenia to be a genetically based brain disorder involving developmental changes that occurred well before the first full-blown psychosis. No one knew precisely what those changes were, but studies strongly suggested that they were real.
Moreover, psychiatric clinics periodically saw adolescents who seemed to be experiencing mild, prepsychosis symptoms. They were "prodromal," in the medical jargon, perhaps destined to develop a full-blown psychotic episode, perhaps not.
Dr. McGlashan and several others saw in these converging threads a possibility: maybe treating young people with drugs before they became psychotic would prevent the illness, and perhaps even help illuminate its cause.
Dr. McGlashan recalled patients at Chestnut Lodge who had spent decades receiving daily psychotherapy, to no avail, before receiving antipsychotic drugs and reclaiming some portion of normal life. One woman spent 18 years at the lodge, barefoot, unkempt, closeted in her room. One day, he said, he looked out a window and saw her going for a morning walk, smartly dressed, wearing shoes; she had recently been given medication and began taking daily walks.
"What right did we have denying her that?" he asked. "Small changes in a person's life, which I think is what we can expect, can make a big difference."
The risks of using drugs to try to prevent psychosis seemed to him moderate. New antipsychotics were becoming available, and, though they could have serious side effects, they appeared to be more tolerable than the older generation of drugs, and to reduce the risk of debilitating, Parkinson's disease-like side effects. So Dr. McGlashan began a study, financed in part by Eli Lilly, giving medication to adolescents considered at high risk for developing psychosis. But almost immediately, there were difficulties.
The test that Dr. McGlashan developed to identify those at high risk proved less reliable than he had hoped, meaning many adolescents would be exposed to drugs needlessly. Participants for the trial were hard to recruit. Mild psychosislike symptoms are rare in adolescents; and some who came in chose to continue seeing Dr. McGlashan or another psychiatrist but did not enter the study.
An ethical debate over the wisdom of early treatment ensued, and not everyone thought the potential benefit was worth the risk.
"Given the likelihood that psychosis is delayed and not prevented by the drugs, and given the severe side effects of the drugs, this is an idea that needs to be taken with great caution," said Dr. Steven E. Hyman, a professor of neurobiology at Harvard and a former director of the National Institute of Mental Health.
And in 2000, Vera Sharav, a prominent patient-protection advocate, wrote to government officials calling the experiment unethical, because "healthy children ? who are not capable of voluntary, informed consent ? are being put at high risk of harm for experimental purposes."
Officials from the federal Office for Human Research Protection began an investigation. About a year later, the agency concluded that the researchers needed to strengthen their informed consent documents to emphasize the side effects of the medication.
The researchers made the required changes, and the trial continued. But in a paper published this month, the authors reported that more than two-thirds of the participants had dropped out, rendering the trial inconclusive. Moreover, those on medication gained an average of about 20 pounds.
The entire process, almost 10 years in the making, has altered Dr. McGlashan's thinking again.
"I'm more pessimistic about all this now," he said. "I don't think the drugs can prevent full-blown psychosis, only delay it." He added, "I think more than ever we need to follow a group of prodromal adolescents who get no drug treatment to see more clearly what happens and refine our understanding of what the prodrome is."
Sitting in his office on a recent Tuesday morning, after having seen three patients taking a total of 10 drugs, Dr. McGlashan sighed. "I've never written so many prescriptions in my life," he said.
He said he had recently gotten a call from someone in England organizing a debate over whether high-risk adolescents should be treated with drugs. "He wanted to sign me up for the pro side, and I said absolutely not," he said.
Now colleagues are watching the progression of his thinking, wondering where his drive for answers will ultimately take him. "It's funny, he seems to be coming full circle," said Dr. Barbara Cornblatt, the director of the Recognition and Prevention Program at Zucker Hillside Hospital in Glen Oaks, N.Y., and an early critic of preventive drug treatment. "I may be more optimistic about early treatment than he is at this point."
