“Bipolar disorder and schizophrenia, and many other types of mental illness, are diseases of the brain and should be treated and studied as such,” say Johns Hopkins researchers.

Does this statement seem a bit obvious and not exactly rocket science? Although it may, this isn’t how the National Institute of Mental Health (NIMH) — the psychiatry wing of the National Institutes of Health — currently views severe mental disorders such as schizophrenia, autism, bipolar disorder and dementia. The NIMH is the largest federal agency that provides research funding on mental disorders.

For the past decade, the NIMH has used a system called Research Domain Criteria (RDoC) to describe all mental illnesses as dimensions of psychological norms that fall along extremes of too much or too little of common personality traits. For example, everyone has minor fears of things such as spiders, heights or snakes. But, having very strong or unmanageable fears might constitute an anxiety disorder.

While this way of thinking may make sense for anxiety, Johns Hopkins physicians argue that for the most severe of mental disorders — such as autism, schizophrenia or bipolar disorder — the approach will lead clinicians and scientists in the wrong direction. These conditions aren’t the result of too much or too little of a normal human trait. Rather they represent a clear-cut shift outside the typical dimensions of human experience.

In every other field of medicine, researchers use animal models of diseases based on genes and their interactions that contribute to disease risk. However, the current NIMH approach directs psychiatric researchers to focus on normal variation. Research on animal models with genetic variations that increase the risk of diseases often doesn’t get funded, they say.

The researchers lay out their thoughts in two commentaries, both published in Molecular Neuropsychiatry, one published in 2018 and the other in the October 2019 issue.

In their first commentary, the researchers argue that the NIMH approach of thinking of mental illness in dimensional terms is like regressing back to Galen’s Humors of the second century, when all illnesses were attributed to the imbalance of one of the four humors: yellow bile, black bile, blood and phlegm. Then, they argue that a biomedical approach using the tools of genetics, neuroscience and imaging can lead to rational targets for therapies. The second commentary is a point-by-point critique of the NIMH system and its flaws. They say that the RDoC system moves away from the proven power of biomedical research, which explores the causes of diseases and their effects on human biology. They add that the RDoC system doesn’t appropriately address the natural history or progression of a disease.

“Using the RDoC system hasn’t advanced the field of psychiatry, diverts attention from achieving an understanding of underlying mechanisms and ultimately delays discovering rational treatments for these diseases,” says author Christopher A. Ross, M.D., Ph.D., professor of psychiatry, neurology, neuroscience and pharmacology at the Johns Hopkins University School of Medicine.

This change in how the NIMH approaches mental illnesses occurred about a decade ago. Leadership at the NIMH initiated the RDoC system with the best motives in mind, in order to encourage neuroscience research to study how cells communicate with one another in the brain. However, this change to the RDoC system happened before modern genetic and other techniques pointed toward specific causes of major mental illnesses.

“No other NIH institute has adopted a scheme so discordant from modern biomedical research practice,” says Ross.

“The NIMH strategy makes psychiatry — and especially psychiatric research — seem like a strange and esoteric endeavor, not part of mainstream biomedicine, with the consequence of stigmatizing the entire discipline, including its patients,” says co-author Russell Margolis, M.D., a professor of psychiatry and neurology at Johns Hopkins.

Now that investigators have identified some genetic and environmental causes, and are beginning to reveal molecular mechanisms behind these disorders, the researchers say that it’s time for the NIMH to readjust their system. These changes should allow for conditions such as autism, bipolar disorder and schizophrenia to be researched and treated as diseases — and not as fringe versions of normal variation. Moving toward a system that values the biomedical approach, comparable with the other NIH institutes, they say, would guide the NIMH to support studies on mechanisms of disease, so researchers can design more targeted therapies for those with different forms of these illnesses. As psychiatric genetics is complex, so are the genetics of many common medical diseases, such as diabetes and rheumatoid arthritis. Nevertheless, in other fields, scientists successfully use modern biomedical technique to address complex diseases. The authors contend that the field of psychiatry and patients with severe mental diseases deserve no less.

Ross received research support from JNJ/Janssen, Teva, Raptor/Horizon, Vaccinex, uniQure and Roche/Genentech unrelated to these publications, and has consulted for Teva, Sage, uniQure, Roche/Ionis, Azevan, Annexon and the Healthcare Services Group. Margolis received grant support from Teva unrelated to the publications discussed here.