An Update on the RAISE Schizophrenia Research Project – An Interview with Jeffrey A. Lieberman, MD

Over the past several issues, Mental Health News has been following the progress of the RAISE project, an NIMH sponsored research study that is examining the role and potential that early and specific interventions can play in the recovery of people that have just been recently diagnosed with schizophrenia. In the interview that follows, Dr. Jeffrey A. Lieberman, MD, one of the principal investigators of the project, gives us an update on his team’s part of the project and gives us some new and important information about how the findings from the RAISE project have the potential to change the way mental healthcare is provided and can radically improve the lives of people who are at risk to develop schizophrenia.

Q: In our continuing effort to cover the progress of this important study, can you help us to better understand its rather complex nature.

A: RAISE (Recovery After an Initial Schizophrenia Episode) is the acronym that names the project which the National Institute of Mental Health (NIMH) is orchestrating to develop and test an intervention that will foster recovery and prevent disability in patients in their first episode of schizophrenia. The RAISE project consists of two studies. Our study is being led by myself at Columbia University and Lisa Dixon at the University of Maryland, along with our colleagues at those institutions and several others across the country. The second study is being led by Dr. John Kane, MD at The Zucker Hillside Hospital on Long Island. Both studies make up two distinct investigations within the entire RAISE project.

The Columbia and Maryland study is based on a very specific type of public mental health model. For us to be chosen to carry out this project, NIMH asked us to come up with an intervention plan based on what we know from research on the natural history and clinical course of schizophrenia and what we have learned from intervention studies that have focused on patients in the early stage of the illness, and then to demonstrate that this optimized intervention could prevent disability and foster recovery in schizophrenia when implemented soon after patients experience an initial schizophrenia episode. To make the results of the study generalizable to the world of mental health care, they wanted us to do this in a way that is ecologically valid – meaning that it must be done in real world and representative clinical settings. In addition, NIMH has also stipulated that the interventions in the studies must be able to be implemented within the context of existing reimbursement systems. This was certainly a challenging task but means that if the study is successful in proving the hypothesis, this early intervention model can then be rolled-out and implemented in clinical practice, almost immediately. In other words, NIMH is looking to fast-track the results of this research into clinical practice rather than wait the usual 8 to 10 years for their translation to practice that is usually required.

To implement these rigorous standards, we have chosen to devise and test our intervention in partnership with two state mental health agencies – The New York State Office of Mental Health (NYSOMH) and the Maryland State Office of Mental Health (DHMH). Consequently, members of the leadership of these agencies including Mike Hogan, PhD, Lloyd Sederer, MD, John Allen and Joe Swinford in NY and Brian Hepburn, MD, and Gayle Jordan Randolph MD in Maryland are working with us on this study.

The commissioners of both state offices of mental health felt that we have a unique opportunity to change the way mental health services are delivered and the way in which future generations of people with schizophrenia are treated in the United States. Both offices of mental health would then agree to provide support for the services at clinical sites that they either license or directly support.

Q: Can you clarify the distinctions between your part of the RAISE project and Dr. Kane’s part of the study?

A: The Kane team is using a network of approximately 30 clinical sites in different locations across the nation, as opposed to our approach of working with two state mental health systems and using the sites that we identify with them within their state-wide systems. There are also differences in the interventions that John’s team and our team are using, such as in the specific choice of one type of psychosocial treatment or another – or one type of pharmacologic approach versus another. Beyond that, the promise that we will each using different approaches take what we have learned from the past 20 years of research in early stage schizophrenia and see if we can apply at the clinical service level in community-based sites.

Q: In your many years of work to improve the lives of people with schizophrenia, has there ever been such a monumental and promising approach to changing the models that are currently being used to help people with schizophrenia?

A: When I began training in the late 1970’s there was a type of therapeutic nihilism that pervaded clinical approaches to schizophrenia – meaning that you could suppress psychotic symptoms but you couldn’t really do that much to rehabilitate or restore people’s lives to what they were before their illness. It was generally thought that people with schizophrenia were doomed from the womb with an inexorably progressive disorder, a dogma that had its roots in Kraepelin’s original formulation of schizophrenia from the late 1900’s and amplified by genetic theories. However, the research that was conducted in the 1980’s, 1990’s and into the 21st Century suggests that if you intervene early and optimally, you can prevent the disability from occurring. This strategy has found its most zealous expression in the form of the early detection intervention prodromal approach to psychotic disorders which has caught on and is being pursued around the world in many countries. However the problem with that approach in terms its readiness for prime time, is that we do not have a specific and reliable means of identifying patients without identifying a significant proportion of so-called false positives – people who may have the so-called prodromal criteria, but never go on to develop a syndromal psychotic disorder. We know that when most people develop syndromal schizophrenia they do not necessarily seek or receive treatment right away. The mean duration of symptoms before a first treatment is generally about a year. We have learned that the sooner we treat them the better. We also know that the fewer relapses that they have after recovery from the first episode, the better their chances for maintaining their recovery and preventing what research now understands as an actual deterioration in the synaptic pathways of the brain. Right now, our ability to test optimal interventions after people do meet syndromal criteria is ready for prime time – and that’s basically what the RAISE study is all about.

Q: So, what you’re saying is that without early intervention, continued episodes of schizophrenia actually destroy synapses in the brain – and a person’s inability to recover at that point is not because they have been so terribly traumatized psychologically after such scary and upsetting events?

A: It’s a matter of brain chemistry and neural circuitry. We know that a chemical disturbance in the brain with the neurotransmitters dopamine and glutamate initially gives rise to psychosis. When it is not stabilized or suppressed in time and is allowed to go on too long then that creates a toxicity which disrupts the integrity of the cell membranes and produces a structural pathology whereby patients lose synapses. The same thing occurs if they have recurrent episodes in the form of psychotic relapses. If this happens repeatedly, this causes the same type of progression from neurochemical pathology to structural pathology. When they get to the point of structural pathology that’s where the medications we have can’t necessarily restore those synaptic connections. To combat this deterioration, we will need to have newer medications with potentially neurotrophic effects and/or with the potential to stimulate neurogenesis, and to potentially exert neuroprotective effects. Our current antipsychotic drugs, although they are good at suppressing the overactive chemical stimulation are not able to produce these neurotrophic and neurogenesis type effects.

The demoralization and discouragement that you referred to in your question can frequently lead to people committing suicide. That generally occurs because people can’t get back to where they were. While they still have some awareness of that they become really dispirited and demoralized by it.

Q: Does this new knowledge of synaptic deterioration also apply to other illnesses such as depression or bipolar disorders?

A: It seems to a lesser degree in bipolar disorder where people have multiple episodes or sustained periods of manic psychosis. They do experience some degree of deteriorative progression but not nearly to the extent that people with schizophrenia do. In terms of depression, there has also been some new research which has explored the possibility of some form of neurotoxicity that occurs – particularly in the medial-temporal lobe in the hippocampus. It is believed that this neurotoxicity may be caused by too high of a level of circulating cortisol that we believe is brought on when people experience high levels of stress. This has not yet been fully verified.

With schizophrenia however, we have upwards of twenty studies that have shown the loss of brain gray matter which we believe reflects synaptic deterioration. MRI studies have shown that there is an actual loss of gray matter in the brain in the frontal and temporal lobes and to a lesser extent to the parietal lobe – which can amount to a loss of from 1-3 percent of brain tissue per year in the initial stages of schizophrenia. This is related to how many episodes a patient has had and how well they have responded to treatment. It is believed that this is a biological marker of this progressive process and this clinical deterioration.

This is why the RAISE project is so important. We know that people are most responsive to treatment at the beginning of their illness and that they are most susceptible at that point to the progression of the illness and its deteriorating effects if the illness is not stopped in the first episode. Therefore, the best time to stop schizophrenia in its tracks is to get people at the beginning of their illness and make sure we treat them as effectively as possible, keep them engaged in treatment, and help them to remain stable throughout the remission processes.

What I think has become almost uniformly observed and understood in patients is that when people get sick for the first time with a psychotic illness – whether its schizophrenia or schizoaffective disorder or even affective psychosis, even if they respond to treatment and have recovered – is that they don’t have a lot of awareness of what they just went through. They understand that something happened to them and they may have been sick, but they don’t know what schizophrenia means and they don’t know that is likely to be a recurring and life-long illness. In addition, they don’t particularly like having to take medications – especially if they cause side-effects. Patients often say “OK, I will take this medication until everything is gone, and then I am going to get back to my life and leave this episode behind me.” This generally occurs because patients don’t like their medications’ side-effects or they believe that they simply no longer have to take them. They lack the awareness that they are on a precipice and flirting with sliding down the slippery slope of deterioration. The next thing you know, they have had a relapse and even if they are treated, they may not get better, and if they do get better, they are still prone to making the same mistake.

What the RAISE project is gearing up to do is to basically say, “Let’s take everything that we believe or has been shown to work and let’s provide this to people in a team-based approach.” Using this approach we want to ensure that they have a smooth course to remission and recovery, keep them there and enable them to re-engage in life and to get re-involved in what they were doing before they became ill – be it school, work, and social activities. We want to prevent people from running away from the psychiatrist and mental health professionals but to stay engaged with them. The hope is that if we do that, people will have a higher rate of recovery, they’ll remain stable and in remission for longer periods of time, and there will be fewer people who will need to ultimately go onto government supports such as Medicaid and Social Security Disability (SSD). So, in addition to the human suffering and productivity dimension to the outcome, there is also an economic cost-effectiveness to the outcomes that the RAISE study hopes to confirm.

Q: All of this knowledge and hope for the project begs the notion that there really needs to be a nation-wide public health campaign to educate people more about schizophrenia and staying in treatment – which because it is such a devastating illness – still remains in the shadows in terms of people’s fears and understanding.

A: Exactly. The first limiting factor is to have a provider network that can actually deliver the kind of care we believe the project will confirm is required. Next, we will need mental health professionals with training in supportive employment, supportive education, case management, cognitive remediation, psychoeducation, peer counseling, psychopharmacology – and to have this expertise available in clinical settings where patients are being seen and treated. Then there needs to be reimbursement for those services. The only way that’s going to be able to happen is if there is evidence that can be taken to mental health care policy administrators and reimbursement agencies – to say that this works not just in terms of our clinical outcome measures but in terms of very hard cost-outcome measurers.

Q: Are you worried that the current socio-economic and political atmosphere we have been under will loom as a cloud over the RAISE project and the recommendations that it will eventually propose be implemented at the national, state and community level?

A: It’s like a best of times, worst of times type of situation. I think on one hand we have an economic situation which is extremely ominous and without clear prospects of getting better in the near future. We also have a health care financing system which has been chronically dysfunctional, and a mental healthcare delivery system which has been fragmented and woefully inefficient. On top of that we now have healthcare reform which threatens to shake things up in a way that we have no idea if it will make things better or worse, and if so, how? You couldn’t pick a more unfavorable or inhospitable situation to try to do something new and innovative. On the other hand, when it comes to psychiatric medicine and mental healthcare, I think the situation is extremely optimistic and very good. Our field is more vibrant than it has ever been in terms of the intellectual dimensions of it, many interested young people are coming into the fields of mental health care and neuroscience research, the science of understanding the brain and how disturbances in the brain that give rise to mental illness has never been stronger. All of these factors are stronger than they have ever been before. Even on the stigma side, there has been progress, and this seems to be getting better all the time. The promise of the RAISE project is that if we are successful in proving our early intervention hypothesis, present this intervention model of service delivery, and get this to be taken seriously on a national level, this can have a huge impact on the lives of future generations of people who develop schizophrenia and economic benefits to the mental healthcare field and our country.

Q: Where are we now in terms of the calendar of the project?

A: It’s not quite a year underway. It will presumably be a 5-year project. We are now finalizing the protocol and selecting the sites and training the people at these sites. We hope to be set to go before the end of this calendar year.

Q: How many people are involved on your study’s team?

A: We’ve got a pretty big multidisciplinary team of over fifty people from a variety of universities and the two state mental health agencies. They include people who are psychiatrists, psychologists, social workers, anthropologists, a number of peer counselors and also people who are selected from different advocacy groups.

Q: Are some of these staff shared between your group and Dr. Kane’s group?

A: No, they are completely independent with no overlap in staff. The only overlap is in terms of the NIMH staff that is working with our two studies.

Q: What final thoughts would you like to give our readers about the RAISE project?

A: Research is something that oftentimes moves forward very slowly, often times at a rate in which the progress being made seems almost imperceptible. Then, suddenly at some point, you get a chance to put it all together and make a great leap forward. I believe that RAISE is one of those opportunities. The NIMH saw this and have really seized the opportunity to take something from the research level and in one fell swoop translate it into clinical practice. With the results of the RAISE project we will have the potential to effect a change in the way mental healthcare is provided and alter the prognosis and prospects of future generations of people who are at risk to develop schizophrenia.

About Dr. Jeffrey A. Lieberman, MD

Jeffrey A. Lieberman, MD, is a physician and scientist who has spent his career of over 25 years caring for patients and studying the nature and treatment of mental illness. Dr. Lieberman is currently is the Lawrence E. Kolb Professor and Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons and Director of the New York State Psychiatric Institute. He also holds the Lieber Chair and Directs the Lieber Center for Schizophrenia Research in the Department of Psychiatry at Columbia and serves as the Psychiatrist in Chief of New York Presbyterian Hospital- Columbia University Medical Center. Dr. Lieberman received his medical degree from the George Washington School of Medicine in 1975. Following his postgraduate training in psychiatry at St. Vincent’s Hospital and Medical Center of New York Medical College, he was on the faculties of the Mount Sinai School of Medicine and Albert Einstein College of Medicine and served as Director of Research at the Hillside Hospital of Long Island Jewish Medical Center. Prior to moving to Columbia University, he was Vice Chairman for Research and Scientific Affairs in the Department of Psychiatry and Director of the Mental Health and Neuroscience Clinical Research Center at the University of North Carolina at Chapel Hill School of Medicine.

Dr. Lieberman’s research has focused on the neurobiology, pharmacology and treatment of schizophrenia and related psychotic disorders. In this context, his work has advanced our understanding of the natural history and pathophysiology of schizophrenia and the pharmacology and clinical effectiveness of antipsychotic drugs. In terms of the latter, he served as Principal Investigator of the Clinical Antipsychotic Trials of Intervention Effectiveness Research Program (CATIE), sponsored by the NIMH. His research has been supported by grants from the National Institutes of Health and the NARSAD, Stanley, and Mental Illness Foundations. His work has been reported in more than 400 articles in the scientific literature and he has edited or co-edited eight books, including the textbook Psychiatry, currently in its second edition; Textbook of Schizophrenia, Comprehensive Care of Schizophrenia; Psychiatric Drugs; and Ethics in Psychiatric Research: A Resource Manual on Human Subjects Protection. He also serves, or has served, as Associate Editor of the American Journal of Psychiatry, Biological Psychiatry, Neuropsychopharmacology, Acta Psychiatrica Scandinavica, Schizophrenia Research, Neuroimage, International Journal of Neuropsychopharmacology, and the Schizophrenia Bulletin.

Dr. Lieberman is a member of the National Academy of Sciences Institute of Medicine and recipient of the Lieber Prize for Schizophrenia Research from NARSAD, the Adolph Meyer Award from the American Psychiatric Association, the Stanley R. Dean Award for Schizophrenia Research from the American College of Psychiatry, the APA Research Award, the APA Kempf Award for Research in Psychobiology, the APA Gralnick Award for Schizophrenia Research, the Ziskind-Somerfeld Award of the Society of Biological Psychiatry, the Ernest Strecker Award of the University of Pennsylvania, the Lilly Neuroscience Award from the Collegium Internationale Neuro-Psychopharmacologicum for Clinical Research and the Exemplary Psychiatrist Award from the National Alliance of the Mentally Ill. He is or has been a member of the advisory committee for Neuropharmacologic and Psychopharmacologic Drugs of the Food and Drug Administration, the Planning Board for the Surgeon General’s Report on Mental Health, the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA), the APA Work Group for the Development of Schizophrenia Treatment Guidelines, the National Advisory Mental Health Council of the National Institute of Mental Health and currently chairs the APA Council of Research and Quality Assessment.

He resides with his wife and two sons in New York City.

About the NIMH RAISE Project

The NIMH RAISE Project is being conducted by two independent research teams—the Feinstein Institute for Medical Research in Manhasset, NY, and the Research Foundation for Mental Hygiene at Columbia University in New York, NY. The Connection Program of the Research Foundation for Mental Hygiene at Columbia University has been funded in whole or in part with Federal funds from the American Recovery and Reinvestment Act of 2009 and the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN-271-2009-00020C. For more information about the overall NIMH RAISE Project, contact the NIMH Press Office and the NIMH RAISE Project Communications Team: Colleen Labbe, Jean Baum, or Christine Ulbricht (301) 435-8687, (301) 443-1018, (301) 443-3366

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