Panel: Mental Health: Research and Development at a Crossroads
By Kathi Hanna, FasterCures Senior Fellow
Considering that one in four Americans will be touched by mental illness in his or her lifetime, we have to ask why we are not investing more research and dollars into the search for better prevention, diagnosis, and treatment. From the neurodevelopmental disorders to the neurodegenerative disorders, the wide range of diseases caused by disruptions of the brain and central nervous system (CNS) can affect us at all and any age, burdening not only those who are affected but also their families and caregivers. At a Partnering for Cures panel, Jay Lombard, chief scientific officer and medical director of Genomind reminded us, "The diseases of the brain affect emotions, our day-to-day life, in essence what essentially makes us human." Yet it is almost impossible to identify anywhere in the field where morbidity and mortality have gone down.
Thomas R. Insel, director of the National Institute of Mental Health at the National Institutes of Health, cited the incredible cost of mental illness, which trumps almost every other category of disease -- $2.5 trillion in 2010, greater than cancer, respiratory disease, and diabetes combined. And it's not as if drugs for these disorders don't sell well; they do. The number one class of drugs in terms of sales is antipsychotics. Antidepressants are not far behind. The problem, said Insel, is that no one knows what to do next. We don't need more 'me-too' drugs; we need better drugs, with fewer side effects and greater effectiveness.
There are many reasons for lack of progress in the field, but the largest factor is the incredible complexity of the human brain. However, scientific breakthroughs and "mindboggling" new tools are stirring renewed interest in a field that once seemed to be at a standstill. This optimism cannot come soon enough for the millions of people struggling on a daily basis with mental disorders.
Jeffrey Nye, a vice president of Janssen Research and Development, LLC, said that there is renewed interest among investors and startups in CNS drugs because "the science of neuroscience is really beginning to open up," citing exciting new advances in imaging and the ability to grow brain cells in culture and view them as they function. Now the task lies in understanding how cellular challenges map to phenotype, and developing biomarkers for early detection of disease, which is critically important. We know that once behaviors are noted, it's too late for prevention. "Behavior is the last thing to happen," Nye said. The underlying disease has been there for some time.
In simplistic terms, psychiatric diseases are diseases of connectivity. Although we are getting better at focusing and zeroing in on the sections of the brain, said Paul Weiss, director of the California NanoSystems Institute, we need to look at the brain from a dimensional rather than categorical perspective, contemplating how the connections work or fail to work to affect health and disease. Insel urged that we "stop thinking of the brain as soup, and rather as a circuit board with very complex connectivity."
Nye added that understanding brain connectivity and more specifically plasticity, especially in children, offers tremendous hope for developing biological interventions that can help, for example, people with post-traumatic stress disorder. Biomarkers will be crucially important as the field progresses because in neurology and psychiatry they provide a "quantitative measure of a qualitative state." Nye said panels of validated biomarkers are going to allow us to preempt the disease diagnosis, to identify and treat disease when treatment will be most effective and before lasting damage is done.
Autism provides an example of how understanding the connections in our brains can inform the search for better therapies. Currently, the best available treatment for the autism spectrum disorders is cognitive and behavioral therapy. In fact, 50 percent of children are greatly helped through these interventions, and 20 percent might even shed the diagnosis. Robert Ring, chief science officer of Autism Speaks, said that studying how behavioral interventions change the progression of autism offers a path toward biomarkers that signal the key aspects of development. Like other disorders affecting the brain, we need to deconstruct autism. Is it 15 or 45 disorders?
Insel said that we have the tools for more effective and accurate diagnoses. The Research Domain Criteria Program is serving as a new approach to classifying psychopathology based on dimensions of observable behavior and neurobiological measures. Its development will help in the deconstruction of the complex and vast array of mental disorders that affect so many.
Panelists agreed that new discoveries deserve increasing attention from investors and drug developers. We need to test more mechanisms, learn from them, and move on. We need to invest in biomarker development that will eventually trump behavior as the leading approach to diagnoses and help differentiate among seemingly similar behaviors and illnesses. We have the opportunity to intelligently combine drug therapy with behavioral and cognitive therapy in ways that complement each other with an additive effect.
At long last, we are at a crossroads in mental health -- a place we have traveled too far to reach.