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Forty years of research, teaching and healing

Medicine@Yale, 2007 - May June

A bold experiment in mental health care reaches a new milestone

When Yale psychiatrist Frederick C. “Fritz” Redlich, M.D., met with newly elected Governor Abraham A. Ribicoff in 1955 to discuss how services for Connecticut’s mentally ill might be improved, he came prepared, according to Benjamin S. Bunney, M.D., the Charles B.G. Murphy Professor of Psychiatry. Redlich, who served as psychiatry chair from 1950 to 1967, had given a great deal of thought to public policy issues surrounding mental health, much of which he later crystallized in Social Class and Mental Illness, a classic 1958 book he wrote with Yale sociologist August B. Hollingshead, Ph.D.

When Redlich appealed to Ribicoff for more services for Connecticut citizens with psychiatric disorders, particularly the poor, Ribicoff shot back, “Well, Fritz, what is Yale going to do about mental health?” In reply, Redlich described the innovative department he had built in his first five years as Yale’s Psychiatry chair. Based on a graduate-school model, the basic and clinical research done by its faculty members formed the foundation for all of its teaching and patient care. Redlich argued that a mental health center adhering to the same philosophy would provide the best, most scientifically sound psychiatric treatment to Connecticut’s citizens.

Over the next four years the Department of Psychiatry and the state of Connecticut hammered out a joint partnership that proposed a wholly new approach to mental health care: a community-based center in which psychiatric treatment, training and research would be brought together under one roof.

In the summer of 1966, with the opening of the Connecticut Mental Health Center (CMHC), Redlich’s vision became a reality. The 65,000 square-foot facility featured space for day patient and outpatient services, 22 beds for inpatients, an additional 22 beds for clinical research, an emergency unit, a 140-seat auditorium, classrooms and a library. Redlich served as the CMHC’s first director; the research facilities were later named in honor of Governor Ribicoff.

Today, the CMHC still stands as a model for research-based mental health training and patient care. Under the direction of Professor of Psychiatry Selby C. Jacobs, M.D., the center complements its scientific and educational roles with inpatient and outpatient psychiatric services for over 7,000 New Haven-area residents each year. As part of the “Yale Tomorrow” capital campaign, the medical school has launched a special fund-raising drive to expand and improve upon CMHC’s facilities.

“The ideas that research would define care and training, and that all parties—psychotherapists, psychoanalysts, social psychologists and biological psychiatrists—would be brought together within one building were really revolutionary,” Bunney says. “The CMHC has an entire floor where one side is basic laboratories and the other is an inpatient research ward for biological psychiatry. This brought basic scientists and clinical investigators together long before the term ‘translational research’ was ever invented. At the CMHC, basic researchers learned about clinical problems and clinical researchers learned the vocabulary of the basic scientists, which made communication possible between these two groups. This in turn spawned all kinds of collaborations, including hypothesis-driven clinical research.”

Beginning in the early 1970s, CMHC scientists led by George K. Aghajanian, M.D., made the first electrophysiological recordings in the brain regions that make use of the neurotransmitters noradrenaline and serotonin. By studying the functioning of these neurotransmitters, these scientists laid the groundwork for drug treatments for opiate dependence, depression, anxiety disorders and attention deficit disorder. Meanwhile, basic scientist Bunney made similar recordings in brain regions that use the neurotransmitter dopamine; Robert H. Roth Jr., Ph.D., studied the biochemistry of dopamine systems; and clinical researcher Malcolm B. Bowers Jr., M.D., studied the dopamine system in patients with schizophrenia. This work lent support to the emerging concept that some of the brain’s dopamine systems are hyperactive in schizophrenia, which ultimately led to a new generation of antipsychotic medications with greater efficacy and fewer side effects.

Another important early research accomplishment at the CMHC, the discovery of clonidine as the first non-opiate treatment for opiate dependence, vividly illustrated the power of Redlich’s integrated model of psychiatry.

In work with animals, Aghajanian and D. Eugene Redmond, M.D., now professor of psychiatry and neurosurgery, found that inhibiting the noradrenaline system with clonidine decreased the symptoms of opiate withdrawal, making rapid and relatively painless withdrawal possible for addicted individuals.

Building on this research, Mark S. Gold, M.D., now Distinguished Professor of Psychiatry at the University of Florida, Professor of Psychiatry Thomas R. Kosten, M.D., and Herbert D. Kleber, M.D., now professor of psychiatry at Columbia University, found that patients being treated at the CMHC for opiate abuse recovered even more rapidly if given an opiate blocker along with clonidine.

John H. Krystal, M.D., who was a student at the School of Medicine at the time, was greatly impressed by the CMHC’s pioneering research on clonidine.

“This research was a landmark in psychiatry,” says Krystal, the Robert McNeil Jr. Professor of Clinical Pharmacology and an expert on post-traumatic stress disorder. “It may have been the first time a clinical condition was understood at the cellular level, leading to the development of a novel treatment based on scientific principles. It exemplifies the Yale tradition of translating basic science insights into treatment advances.”

The unusual productivity of the CMHC’s translational approach continued into the 1990s, as Eric J. Nestler, M.D., Ph.D., now the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research at UT-Southwestern Medical Center in Dallas, led groundbreaking studies on the neurobiological basis of drug addiction. Today, Ronald S. Duman, Ph.D., the Elizabeth House and Jameson Mears Professor of Psychiatry, is one of the leading proponents of the neurogenic theory of antidepressant drug action, one of the most significant advances in the understanding of mood disorders in decades (see related story).

This record of achievement is all the more remarkable given the organizational and cultural differences between a university and a government agency, say the psychiatry department’s state partners at the Connecticut Department of Mental Health and Addiction Services (DMHAS).

According to Thomas A. Kirk Jr., Ph.D., DMHAS commissioner, “The fact that this partnership has been sustained so long is really a statement about the shared commitment to clinical services, research and teaching. The National Alliance on Mental Illness recently reviewed the mental health systems of each of the states and assigned grades. Connecticut was one of the top two states in the nation, and I think our relationship with CMHC was clearly a contributor to our high grade.” DMHAS Deputy Commissioner Wayne Dailey, Ph.D., agrees. “A lot of the policy questions that we deal with are pretty complicated, and they affect thousands of people’s lives. In a university setting, tenured faculty have a rather long view of things, but the median term of office of a commissioner of mental health in the United States is about 21 months,” Dailey says. “There’s a lot of pressure on commissioners to act quickly, and often the evidence and data available to a commissioner in making a key policy decision are not very good because of that pressure. But when you have a university partner that is bringing research that’s been used in developing evidence-based practices into the policymaking process, you have a much stronger basis for making those decisions.”