Precision Medicine for Mental Disorders

Precision medicine seems to be the new hot topic in the research world. President Obama spoke about precision medicine in his State of the Union speech on January 20, his budget released today requests $215M for precision medicine, and NIH just announced plans for a study of a million or more volunteers to explore precision medicine. What precisely is it? The White House website has a useful definition: getting the right treatment at the right time to the right person. The President, in an event devoted to precision medicine in the East Room last Friday [January 30, see video, below], told the story of ivacaftor, a drug that effectively treats the underlying causenot the symptomsof cystic fibrosis, but works in only 4% of patients who have a specific mutation in the gene causing this disease.

Most of the conversation about precision medicine focuses on cancer. Because cancer is a disease of genetic mutations leading to unregulated cell division, defining the precise mutations in the affected tissue have already led to breakthrough treatments for both blood and solid tissue cancers. In fact, the same mutation can occur in different parts of the body, so cancer is increasingly diagnosed in terms of its genetic and molecular signature rather than the tissue of origin. Part of the proposed precision medicine plan will involve scaling up efforts at the National Cancer Institute to find these mutations and to develop drugs or biologics as treatments.

What does precision medicine mean for mental health? Our version is the Research Domain Criteria (RDoC) project, which aims to develop more precise diagnostic categories based on biological, psychological, and socio-cultural variables. It is certainly possible that we may find specific mutations in relevant brain circuits that explain some cases of schizophrenia, bipolar disorder, or autism, just as mutations in the tumor explain cancer. NIMH has supported research on inherited genetic risk for several years; a new initiative on another class of mutations, somatic mosaicism (the term for mutations that develop after fertilization), will launch this year. But more likely, precision medicine for mental disorders will not come from a single genomic glitch. Rather, like many other areas of medicine, many genes each contribute only a small amount of vulnerability as part of an overall risk profile that includes life experiences, neurodevelopment, and social and cultural factors. RDoC assumes that we will need many kinds of data to reach precision, more like triangulating to find your position on a map. These data will draw from many sources, including symptoms, genotype, physiology, cognitive assessment, family dynamics, environmental exposures, and cultural background.

I know that RDoC sounds more complex than the cancer version of precision medicine, but that is the nature of the problem. For now, we need to embrace the complexity to identify the simpler, actionable categories that can be used in the clinic. The rationale for this approach is no different from what the President talked about for cancer or cystic fibrosisgetting the right treatment at the right time to the right person.

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Precision Medicine for Mental Disorders