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Schizophrenia - seeking solutions

The year was 1957, and young Will Carpenter had to make an important decision. As a senior and standout athlete at Wofford College in South Carolina, he had already decided on a career in medicine. But Will’s prowess on the football field had attracted the attention of the Baltimore Colts, and the team offered him a job as kicker and receiver. The prospect of playing professional football on the same team as legendary quarterback Johnny Unitas was tempting to say the least. The Colts even promised to pay his way through medical school if Will would only say “yes.” But after talking to his family and his minister, Will Carpenter turned them down flat. The next year, the Colts went on to win the championship, beating the New York Giants in a thrilling overtime game that put the NFL on the map.

There is still a tinge of regret in Will Carpenter’s voice as he recalls that life-defining decision. But, today, as director of the Maryland Psychiatric Research Center (MPRC), William T. Carpenter Jr., MD, believes he made the right choice. “I really, really wanted to play football,” he says, “but the John Calvin work ethic buried deep within me was just too strong. I felt committed to pursue a career with a high social value.” And that he did. In a 40-year career devoted to the understanding and treatment of severe mental illness, Dr. Carpenter has become one of the world’s preeminent psychiatrists and transformed the MPRC into an internationally recognized center for “cutting-edge” schizophrenia research.

Raised in Rutherfordton, North Carolina, a small farming community between Asheville and Charlotte, the road to medical school was more than just unlikely. As Dr. Carpenter puts it, “it was just plain weird.” After high school, his mother took him to a local junior college for vocational testing. Given his natural athletic ability and outgoing personality, Will was thinking about becoming a football coach. But after seeing the results of the aptitude test, the psychologist who evaluated Will had other ideas. “Your interests are in science and music,” he told Will, “but you are not a very good musician.” With a strange sense of certainty the psychologist finally concluded, “You will have a career in medicine, and you will specialize in psychiatry.” Will took the advice to heart and never looked back.

After attending the Bowman Gray School of Medicine at Wake Forest University, Dr. Carpenter interned at North Carolina Baptist Hospital and received his post-graduate training in psychiatry at the University of Rochester Medical Center. At Rochester, he studied under Dr. John Ramano, a world-renowned medical educator. In doing so, Dr. Carpenter found a mentor, and discovered the primary focus of his life’s work. Dr. Ramano concentrated his research on schizophrenia—a tragic, debilitating and chronic form of mental illness marked by psychotic delusions and auditory hallucinations.

William T. Carpenter, Jr.

Schizophrenia affects approximately one percent of the world’s population, but in the 1960s little was known about how to diagnose and treat the disease effectively. Dr. Ramano stressed the need for evidence-based research and encouraged his students to tackle psychiatry’s leading problem. The training inspired an intense curiosity about every aspect of schizophrenia—a curiosity that would eventually lead Dr. Carpenter to Baltimore.

Dr. Carpenter followed a career path taken by many of the nation’s leading clinician-scientists. In 1966, he went to work as a psychiatric researcher at the National Institutes of Mental Health (NIMH) in Bethesda, where he studied the psychobiology of affective disorders. Next, he became a collaborating investigator in the World Health Organization (WHO) international pilot study of schizophrenia. At the WHO, Dr. Carpenter was able to indulge his interest in all facets of schizophrenia research. He studied prognosis, diagnosis, and treatment outcome. “I am an idealist and an optimist by nature and focusing on schizophrenia allowed me to express that as a doctor,” he said.

After brief stops at the Albert Einstein College of Medicine and Columbia University in New York, Dr. Carpenter came to the University of Maryland School of Medicine in 1977 as professor of psychiatry and director of the Maryland Psychiatric Research Center. Located on the campus of the Spring Grove Hospital Center in Catonsville, the MPRC had a lackluster reputation, insufficient resources to conduct serious clinical research, and was one step away from losing its state funding. But for Dr. Carpenter, the MPRC was a diamond in the rough.

“When I came to this center in 1977, there were no beds, no clinics and no competitively funded scientists,” recalls Dr. Carpenter. “It was an unlikely location to attract world-class scientists.” But Dr. Carpenter provided the MPRC with what it needed most, strong leadership and a vision for the future. Under Dr. Carpenter, the MPRC’s primary mission would be the study of schizophrenia—to understand the causes and symptoms of the disease, to improve diagnostic techniques and discover innovative treatments.

Before any of these goals could be achieved, Dr. Carpenter would have to create a center that would merge clinical care and basic neuroscience research under one roof—a tall order in the competitive world of academic research. The MPRC would have to provide a high level of care for patients willing to volunteer for experimental treatments and clinical trials. That meant hiring psychiatrists, psychologists, neuroscientists, social workers, nurses, and research assistants, not to mention administrators and support staff. It might have taken some people years to institute such a dramatic change, but Dr. Carpenter pulled it off in a matter of months.

Among the first of many talented researchers to be recruited by Dr. Carpenter was Carole A. Tamminga, MD, a young researcher from the NIMH. Dr. Tamminga took on the task of developing the MPRC’s inpatient research program. Designed to study the causes of severe mental illnesses, the inpatient program now has 42 research beds.

Carpenter also established an outpatient research program and developed a neuroscience program to investigate the nature of brain dysfunction in schizophrenia. The schizophrenia related disorders program was set up to study the biology and the genetic basis of the disease. The four programs are separate, but interdependent, driven by 20 faculty researchers.

“Will created an interactive environment where clinical and research staff can work together toward a common goal,” explains Dr. Tamminga, who is now the MPRC’s deputy director. “And because of his support and encouragement, we have been extremely successful. Dr. Tamminga considers Dr. Carpenter a model clinician-scientist. “Will is not only bright and creative, he is a good teacher and mentor.”

At six feet six inches tall with a shock of longer than average white hair and beard, Dr. Carpenter presents a commanding figure. But his personal warmth and engaging personality, combined with a slight southern drawl, seem to invite informality. Within minutes, people who start out by addressing him as “Dr. Carpenter,” find themselves calling him “Will.” They just can’t help it. “There is just no reason for Will to be pretentious,” explains Dr. Tamminga. “His credentials and accomplishments speak for themselves.” Indeed, in addition to his administrative responsibilities at the MPRC, Dr. Carpenter remains a hands-on researcher. He has authored over 200 clinical and scientific articles, books and book chapters.

Some of the MPRC’s most important research has focused on the neuroanatomy of the schizophrenic brain. One series of studies proved that different structures of the brain are responsible for different symptoms. “The part of the brain involved in the hallucinations is separate from the part of the brain connected to the lack of emotion and drive,” says Dr. Carpenter. Since 1979, MPRC researchers have used cutting-edge neuroimaging technology to understand the neuroanatomic pathology of Schizophrenia.

Sometimes, what you don’t find is of paramount importance. When scientists hypothesized that a new anti-psychotic drug would be more effective than other drugs on the market, the MPRC decided to put the medication to the test. The drug’s chemical make-up appeared promising, but MPRC researchers clarified the drug’s limitations, opening the door to new treatment approaches. MPRC research has also shown that some anti-psychotic drugs can be just as effective in smaller doses, helping to reduce side-effects.

In a current study, MPRC researchers are trying to determine why most schizophrenic patients are unable to work, even after receiving treatment. “It appears that the major symptoms of the illness, such as hallucinations and delusions, do not fully explain the long-term disability many patients experience,” says Dr. Carpenter. However, a small but significant number of people with schizophrenia are able to hold competitive employment. “We hope that by studying these people we can identify the strengths and skills needed for job success,” he continues.
Of all the forms of severe mental illness, schizophrenia may be the most devastating and difficult to treat. Patients are often stricken with the disease suddenly in their late teens or early 20s. Some may hear voices (auditory hallucinations), experience paranoid delusions or disorganized thinking, or exhibit bizarre or inappropriate behavior. The extent and severity of the symptoms can vary widely from patient to patient.

“There have been no major breakthroughs in treating schizophrenia since anti-psychotic medications were introduced 45 years ago,” says Dr. Carpenter. “These drugs treat the delusions, hallucinations and disorganized thinking associated with the disease—what we call the “positive” symptoms. But they do nothing to alleviate the “negative” symptoms. Patients with negative symptoms are limited in their ability to experience and express emotion, have reduced drive and motivation, and function poorly in occupational and social situations,” says Dr. Carpenter. “These symptoms have an enormous impact on a patient’s quality of life and their chances for long-term recovery.” In rare cases, the schizophrenic mind can be a threat to the safety of others.

It was just such a case—the historic case of John Hinkley Jr.—which thrust Dr. Carpenter into the national spotlight nearly 20 years ago. Hinkley is the deranged man who fired the shots outside the Washington Hilton Hotel in 1981, wounding President Ronald Reagan. Press Secretary James Brady, as well as a secret service agent and a police officer were also shot in the assassination attempt. As the defense psychiatrist, Dr. Carpenter took the stand at Hinkley’s trial, providing compelling testimony about the degeneration of Hinkley’s mind.

“It was a very tragic and sad situation for all involved,” remembers Dr. Carpenter, who interviewed Hinkley for 45 hours. Obsessed with actress Jodie Foster, Hinkley thought he could impress her by imitating a violent character in the movie “Taxi Driver,” which he saw 16 times. During three days of riveting testimony, Dr. Carpenter described Hinkley as a troubled and withdrawn adolescent who eventually became unable to tell the difference between his own delusions and reality. Dr. Carpenter’s diagnosis: schizophrenia. The jury agreed with Dr. Carpenter, and Hinkley was found not guilty by reason of insanity.

Some of the MPRC’s most important research has focused on the neuroanatomy of the schizophrenic brain. One series of studies proved that different structures
of the brain are responsible for different symptoms.

“At the time, the prospect of a successful insanity defense in such an emotional, high profile case was unthinkable,” says Dr. Carpenter. “But I was lucky that the defense attorneys and Hinkley’s family were committed to revealing the truth, and the judge allowed me to explain Hinkley’s illness to the jury.” In addition to giving the field of psychiatry new credibility, Dr. Carpenter’s testimony also increased public awareness about severe mental illness. Today Dr. Carpenter calls the Hinkley trial “one of the most interesting and dramatic experiences of my life.”

It is a life that continues to be devoted to making life better for the millions of people who suffer from schizophrenia. In 1999, the MPRC entered into a six-year collaboration with the Swiss pharmaceutical company Novartis Pharma AG to discover new therapies for schizophrenia. The $24 million grant—which at the time was the largest in medical school’s history—will help scientists gain a better understanding of the disease at the molecular level and to test new drug treatments. Dr. Carpenter is the primary investigator for the research, which will focus on finding treatments for schizophrenia’s “negative” symptoms.

After decades of laying the groundwork, Dr. Carpenter believes the MPRC is now poised to make a major breakthrough in schizophrenia treatment. “The Novartis collaboration provides us with unprecedented access to human genetic information and the ability to test novel compounds,” he says. And Dr. Carpenter knows the MPRC team is up to the challenge. “I am privileged to work with a network of creative and independent scientists who make each other better. My job is to make everyone responsible for reaching their farthest star,” Dr. Carpenter says.

There is no doubt that Dr. Carpenter has accomplished that mission. And there is no doubt that in 1957, young Will made the right decision. 

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