Balancing Immediate Needs with Future Innovation

NIMH, like all Institutes at NIH, has an advisory council that meets three times each year. The National Advisory Mental Health Council (NAMHC) is a distinguished group of scientists, advocates, clinicians, and policy experts. Each of our meetings includes a closed session to review individual grants considered for funding and a session open to the public that engages this diverse group in discussions about the larger issues that guide NIMH funding.

At last week’s session, we heard a recurrent tension around one such larger issue. Some members of Council bear witness to the poor quality of care, the unmet medical need, and the diminishing investments by states on behalf of people with mental disorders. They reasonably ask, “How are we ensuring that the science that NIMH has produced is implemented where the need is greatest?” They also question on the pay-off of genetics research. After all, two decades after the gene for Huntington’s disease was identified, we still have no effective treatments, and Huntington’s disease is genetically far simpler than schizophrenia or bipolar disorder. In contrast to so many neurological diseases, we have effective treatments for schizophrenia and bipolar disorder. NIMH should be investing to ensure these are available.

The opposing argument runs something like this. There has been no major innovation in therapeutics for most mental disorders since 1960. Current treatments are not good enough for too many. Rather than investing scarce dollars for incremental improvements or increased dissemination of mediocre interventions, we need invest in the fundamental science of brain and behavior so that we can understand how to develop better treatments.

While I may have oversimplified the two sides of this debate, the divide is substantial. Some advisors want more funds in services research; other advisors want more funds in basic neuroscience. Some are thinking of the immediate needs; others are focused on the paradigm shifts that may be revealed by another decade of research. And with the NIMH budget stretched, tough choices must be made.

One answer, of course, is to keep the NIMH portfolio as diverse as the Council. Two important projects exemplify this diversity. The Recovery After Initial Schizophrenic Episode (RAISE) study has invested over $25M into defining a toolkit for states that will optimize medical and psychosocial care after a first psychotic experience. Knowing that this investment will only be successful if it transforms how states support services and which services they support, the NIMH team has worked to develop an implementation plan for RAISE. The Developmental Neurogenomics project  has invested close to $25M in defining the normal and abnormal patterns of cognitive and neural development of 10,000 children so that we can understand for the first time the variable pathways by which brain and behavior change across adolescence. Recognizing that we know very little about this critical period of human brain development, NIMH has been focused on describing the biology of brain development, from DNA to RNA to proteins to cells and connections.

Our approach for achieving balance in the research portfolio is guided by a few simple principles. First, we need to focus on both short-term and long-term objectives. The short-term needs for better implementation of evidence-based practices, increased adherence to current treatments, and engagement of payors and policy makers are critical for NIMH. Like RAISE, many of these issues will be addressed via contracts rather than grants. And some projects will require partnerships with HMOs or state mental health departments. But there are also tough, scientific questions, like those posed by the Developmental Neurogenomics project, which will only be answered via fundamental discovery science.

Second, current treatments are not effective enough. While there have been important innovations in the behavioral treatment of borderline personality disorder and family interventions for anorexia nervosa, for many disorders we have little to show after four decades of pharmacologic research except reduced medication side-effects. In spite of exuberant sales of medications and broader use of psychosocial treatments, we are faced with outcomes that are just as unacceptable for serious mental disorders as they would be for cancer. Briefly stated: in many cases patients receiving the best of current care are not recovering. We can blame the mental health care system, the absence of insurance or providers, or stigma, but the inconvenient truth is that our treatments are not good enough. NIMH has a critical role for ensuring that more effective medications, devices, and psychosocial treatments are available in the future.

Finally, we have an unprecedented opportunity for progress, real progress, in understanding mental disorders. The answers are likely to be more difficult and more complex than cancer or many single gene disorders, but the tools are now becoming available. High throughput sequencing for DNA and RNA, whole genome epigenomics, high resolution imaging of the human brain, connectomics—all of these tools are giving us a first opportunity to understand mental disorders at many levels beyond the reported symptoms or the observed signs. What the EKG did for cardiology, the bacterial culture did for infectious disease, and molecular biology did for oncology, neuroscience should provide for the study of mental disorders.

Sixty years ago, the nation faced a similar short-term vs. long-term debate about polio. The needs were growing and the causes were unknown. Some wanted funds invested only in better services, including improved iron lungs. Others argued for investing in a vaccine with a long-term goal of eradication. As David Oshinsky explains in his outstanding retelling of this debate, the government went with the services approach, leaving advocates and families to raise funds for vaccine development.¹ Let us hope we don’t short-change our grandchildren, sixty years from today, by failing to invest in the long-term promise of more effective diagnostics and therapeutics for mental disorders.

Reference

1. Oshinsky DM, Polio: an American story, Oxford University Press, 2005