From Inconvenient Truth to Urgent Opportunity

Elizabeth A. Phelps, New York University

In my first Observer column as President of APS, I wrote about the maturation of neuroscience and explored what’s next in psychological science. This month’s guest columnist is Thomas R. Insel, the director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health. Below, Insel outlines the novel approach NIMH is adopting in its efforts to understand and treat mental illness, and highlights the importance of psychological science in this endeavor. –Elizabeth A. Phelps

Over the past decade, the National Institute of Mental Health (NIMH) has sharpened its focus on serious mental illness as diverse brain disorders. For some, this suggests a trend away from psychological science. In fact, psychological science has never been more important. In this column, I hope to explain how we are changing our approaches to diagnostics and therapeutics and why cognitive science, systems neuroscience, and basic behavioral science will be critical for progress if we are to improve outcomes for the millions of Americans with serious mental illness.

Thomas R. Insel, National Institute of Mental Health

Why do we need better diagnostics and therapeutics?  While we have seen profound progress — measured as reductions in morbidity and mortality — for heart disease, cancer, and HIV/AIDS, the inconvenient truth is that there has been little or no evidence of better outcomes or reduced mortality for any mental disorder. Indeed, suicide rates, often considered a proxy for the mortality from serious mental illness, have trended up over the past two decades while many other sources of medical mortality, as well as deaths from homicide and traffic accidents, have been falling.

Why have we not seen advances on par with other areas of medicine? Some would point to stigma, lack of access, and lack of funding for mental health services. These are critical contributory factors, but we also need to admit that our understanding of brain and behavior remains far behind our understanding of cardiovascular function, cancer biology, or infectious diseases. Without a deeper understanding and better treatments, increasing services may not reliably improve outcomes. We need better science as well as better service.

Our narrow approach to diagnosis is hampering the quest for better science. Currently, the diagnosis of mental disorders is based exclusively on clinical symptoms and signs. Over the past decade, cognitive science, neuroimaging, and genomics have provided powerful new tools for understanding mental disorders, but the findings often do not match our current diagnostic categories. For many, this mismatch has suggested that these tools are not useful. However, if we are to create a diagnostic system that is biologically as well as psychologically valid, shouldn’t we begin with these findings from cognitive science, neuroscience, and genomics and build categories from this foundation?

That is the fundamental concept underlying the Research Domain Criteria (RDoC) project that NIMH has proposed as a framework for research on mental disorders. While the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases will still be useful for providers and payers, we are asking the research community to:

Shift from these clinical consensus criteria to deconstruct current categories (e.g., major depression or autism spectrum disorder) into subtypes that are built on shared cognitive domains or biological features.

Look at cognitive domains or biological features across the current categories, defining dimensions of function (e.g., reward or negative affect or cognitive control) that map more precisely to known brain systems and relate more accurately to fundamental research on brain and behavior.

This is a years-long effort, but our goal is to have a diagnostic system that will use many levels of analysis, from genomics to social, to provide more personalized and potentially more successful approaches to treatment. Therapeutics also needs to be transformed. We need better medical and psychosocial treatments. Most clinical trials have focused on proving the efficacy of a new medication or psychosocial intervention. The inconvenient truth here is that, as with diagnostics, we just don’t know enough. The lack of targets for new medications has led most pharmaceutical companies to abandon this area. While we have seen innovations in psychosocial treatments, we still cannot predict who will respond best to these interventions, we do not understand the mechanism of action, and we have little evidence for the required dose or duration.

NIMH will look for clinical trials based on experimental therapeutics or experimental medicine. We are looking for interventions as probes. Randomized clinical trials will still provide data on efficacy, but even more important, they will offer insight into the disorder and targets for future development of therapeutics. The two critical questions we will ask are: “What will this trial teach us about the disorder? What will we learn if this trial fails to show efficacy?” A trial will need to demonstrate engagement of a target or mediator (e.g., a cognitive function or neural circuit) if it is to teach us about the disorder and prove informative, irrespective of the clinical response.

As we are pushing forward to make this transformation in diagnostic approach, it remains important to ensure that those with mental illness seek and receive treatment. Current therapies help many to recover and lead productive lives. Research will continue to add to the evidence base for treatment efficacy and improved access.

Transforming diagnostics and therapeutics may sound more like the menu for oncology than psychology. For RDoC and experimental therapeutics, psychological science will be essential. If we are to turn inconvenient truths into urgent opportunities, we need to provide those with serious mental illness the very best science of brain and behavior.

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