Dr. Thomas Insel, director of the National Institute of Mental Health, shares his view on the current landscape of mental health research

From The Quarterly, Spring 2011

Viewing the state of mental health in the United States from his vantage point as director of the National Institute of Mental Health (NIMH), Thomas R. Insel, M.D., perceives an uneven landscape.  The good news, he says, is that “the science has never been better. By almost any measure, the opportunities we have today for getting to understand the major mental illnesses from autism to Alzheimer’s disease to eating disorders to the psychotic illnesses and mood and anxiety disorders are unprecedented. We’re gaining a foothold on many levels, from the molecular to the behavioral, or as we say at the NIMH, ‘from the genome to the culturome.’”



He does not, however, see comparable progress concerning the prevalence and treatment of mental illnesses. Under his leadership, the NIMH recently initiated a comprehensive program aimed at leveling the field, a strategic plan to narrow the gap between what’s discovered in the lab and what gets applied in the clinic.



Gap between great science and better treatments

Dr. Insel’s appraisal draws upon a broad perspective. He began his career as a practicing psychiatrist. He turned to laboratory work doing basic research to study the neurobiology of social behaviors during an earlier stint, in the 1980s, at the NIMH. Later, as a professor of psychiatry at Emory University, he founded a National Science Foundation funded Center for Behavioral Neuroscience and led an NIH Center for Autism Research. He also directed the Yerkes Regional Primate Research Center from 1994 to 1999. Dr. Insel was awarded a NARSAD Distinguished Investigator Grant, in 2001, to explore whether variations in two genes play a role in social behavior in schizophrenia and autism. He was elected to the Brain & Behavior Research Foundation (then NARSAD) Scientific Council in 1999, a volunteer position he left when he was appointed to his present post in 2002.



“When I rejoined the NIMH after 20 years away from clinical care most of the changes I saw were not for the better,” he says. “Treatments for the most part had not improved, nor had outcomes when measured by such indices as employment, suicides and homelessness.

Access to care had actually declined.  While the research has certainly taken off, the areas where there has been the most progress, genetics and neuroimaging, haven’t yet had any real impact on care. The country has an annual rate of 35,000 suicides. In the military, we’re

losing more soldiers to suicide than to combat.”



One treatment area where Dr. Insel does see an advance is the use of the medication clozapine to treat schizophrenia. Clozapine was tested in the late 1980s on patients with schizophrenia resistant to other treatments by Dr. Herbert Meltzer, a member of the Brain & Behavior Research Foundation Scientific Council, and others at Vanderbilt University. At present, however, clozapine is used by fewer than one percent of people in the United States with schizophrenia, mainly because of concerns about a rare but potentially fatal side effect. Dr. Insel points to schizophrenia as an example of how genetic research can be applied to looking for biomarkers as has been done in other areas of medicine. This would identify those at risk, a quest currently underway.



The disparity between research and care in mental health can be explained, Dr. Insel says, by the sheer complexity of brain disorders. “We know now that no single gene is going to explain vulnerability to schizophrenia nor one neuroimaging result make possible a diagnosis or identify which patients should receive which treatment,” he said. “We may have had that hope a decade ago, but that was before we learned how complicated these disorders are. That’s not a reason to give up the same was true for cancer as recently as 10 or 15 years ago. Rather, it’s a reason to accelerate our efforts.”



Mental health care: ‘separate and unequal’

Stressing the importance of integrating mental health into the larger health care picture, Dr. Insel observes that mental health continues to be ‘separate and unequal,’ with mental illnesses still considered qualitatively different from other illnesses.  



 “These are uncertain times economically, and difficult times in the provision of health care both for mental health and for other medical problems. It’s important for people to realize the public health challenges in front of us, to recognize that these are very serious brain disorders that are too frequently fatal. So understanding the severity of these illnesses is where one needs to start. And severity here is measured in morbidity and mortality.”



Strategic plan to get to better results: The four Ps

At this writing the U.S. government is in a heated budget debate that could mean cuts to research funding at the national level. In this climate Dr. Insel remains focused on effectiveness. “The challenge now is to make sure the funds we do have are used for the greatest impact,” Dr. Insel says. This is where the NIMH strategic plan what he and his colleagues call “the four Ps” comes in.



The first P is for pathophysiology. As Dr. Insel explains:

“We don’t really understand the pathophysiology of any of the mental illnesses in the way we now understand many medical problems. It’s imperative we make a large investment toward learning the causes and mechanisms of these disorders.”



The second P is preemption. Brain disorders result from missteps in brain development, which raises the possibility of intervening at an earlier stage of illness. In schizophrenia, for example, psychosis, the point at which most people are first diagnosed, is a relatively late stage. “It’s like the way we used to diagnose coronary artery disease only after a myocardial infarction,” Dr. Insel says. “We want to be able to identify biomarkers early in the cycle so that we can come up with more effective ways to preempt disability.”



The third P is for personalized medicine. Syndromes such as schizophrenia, autism and depression represent extreme-ly heterogeneous disorders. As a result, treatments that work for one person often don’t work for another.  “Understanding how to tailor treatments to the needs of each individual is a major priority. This requires a different kind of clinical trial where the focus is on being able to identify not just differences between treated and untreated individuals, but exactly who is responding to which treatment and why,” Dr. Insel says.



The fourth P stands for public health impact, or, as Dr. Insel puts it, “getting to the endgame having the measures that will reduce disability, unemployment, homelessness, suicide. It’s being able to ensure that people can truly recover and have the opportunity to participate fully in society.”



Joining forces to accelerate progress

Partnerships that bring together different sectors of the health care community for research and treatment development might be called the “fifth P.” Dr. Insel points to the example of a current plan for autism research that includes a database of 50,000 individuals to serve as a

repository for both publicly and privately funded studies. In another instance, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), funded in part by the National Institutes of Health (NIH), partnered with pharmaceutical companies to study Alzheimer’s risk.



“Partnerships become even more critical when funding is tight. There’s an old expression that says if you want to go fast, go alone. If you want to go far, go together. We want to go both fast and far, so we have to figure out a way to do many things together. I think we have done this quite well in autism, where there is a coordinating body that brings together nonprofits along with the different federal agencies to create a strategic plan for research, to figure out where the gaps are and to close those gaps by working together.



“We’ve done that in some very concrete ways, from specific studies that had to do with genetics and looking for biomarkers through sibling studies to now creating a database that has more than 50,000 individuals in it that will be the kind of repository for both the publicly funded and privately funded research. So that’s a partnership that has grown up over the last 4 or 5 years. I think it’s really making a difference for people with autism and their families.”



Although such partnerships become even more critical when funding is tight, the pharmaceutical industry has largely retreated from the development of psychiatric medication, which Dr. Insel warns “should be of great concern to anybody who cares about mental illness since treatments generally are developed by industry.”



In another kind of partnering, Dr. Insel acknowledges, “the vital role nonprofits play in supporting early stage investigations,” what he calls “venture science.” The Brain & Behavior Research Foundation is the nation’s largest private funder of mental health research. Of the organization’s mission he says: “What is most difficult for scientists starting out, sometimes even for established investigators exploring a new area of interest, is getting that first small grant that allows them to collect the pilot data they need to be able to apply to NIH for funding.



“That certainly was true for me and I know the support from Brain & Behavior Research Foundation has been critical to countless psychiatric researchers.”



In his NIMH Director’s Blog for March 29, Dr. Insel stated: “We are living through an extraordinary period of discovery in neuroscience, analogous to the exuberant periods of theoretical physics a century ago or microbiology a half-century ago.” He reiterated this message for the readers of this article, asserting: “These are scientifically the best of times, and that’s an enormously hopeful sign for the future.”