Research on Biomarkers for Mental Disorders
NAMHC Concept Clearance:
Wayne K. Goodman, M.D.
Director, Division of Adult Translational Research & Treatment Development (DATR)
This initiative will solicit applications proposing novel approaches to the identification, characterization, and validation of biomarkers and/or biosignatures (integrated profiles of biomarkers and behavioral indicators) of major mental disorders.
One of the greatest challenges for management of mental disorders in the post-genomic era is to “catch up” with the rest of clinical medicine with respect to diagnostic, prognostic, therapeutic, and preventive strategies based on the relevant biology, pathogenesis, and pathophysiology of the disorders of interest. Physicians in many specialties are now able to call upon a vast array of directly relevant biomarkers to accomplish this cardinal task. By contrast, physicians treating mental disorders rely almost exclusively on clinical observation and historical data obtained from patients and other informants.
Numerous biomarkers are available for use in routine medical practice of diagnosis, prevention and treatment. For example, the management of diabetes has been aided by the availability of the serum biomarker hemoglobin A1c. In the case of cardiovascular disease, there are biomarkers which confirm a later stage event (e.g, cardiac enzymes for myocardial infarction) or help predict disease risk or response to treatment (e.g., lipid profile, C-reactive protein). Despite tremendous progress in basic neuroscience, not a single biomarker has been developed with established clinical use in the management of major mental disorders outside the area of substance abuse.
This initiative aims to break this intellectual logjam by reaching well beyond NIMH’s typical applicant pool and encouraging high levels of innovation. Many of the elements necessary for a successful outcome are close at hand. Emerging molecular tools and screening methods relevant to mental disorders are becoming more robust at a logarithmic rate. Efforts to identify and characterize susceptibility genes for schizophrenia and bipolar disorder appear to be bearing fruit. New and promising imaging tools continue to be developed. In all, the scientific landscape appears to offer fertile ground for biomarker/biosignature discovery. Attracting a broader array of innovative scientists to the endeavor may be the missing element. As is the case for diabetes mellitus, it is widely assumed that the current phenotypes of major depression, bipolar disorder, schizophrenia, autism spectrum disorders, and obsessive-compulsive disorder reflect “families” of etiologically heterogeneous disorders. Accordingly, biomarkers may not map precisely onto the current nosological system. A biomarker (or biosignature) may be associated with either a subtype or endophenotype of an existing disorder; it may also correspond to a dimension or domain of pathology (e.g., psychosis) that cuts across multiple disorders.
The identification, characterization and validation of biomarkers/biosignatures for the major mental disorders would facilitate accurate prediction of disease risk, course, and therapeutic responses and ultimately lead to knowledge-based treatment and preventive strategies.