29 March 2010. Just as SRF has finished posting our look at the state of schizophrenia genetics (see SRF related news story), eight prominent geneticists and neurobiologists (including three Nobel laureates) have added a timely postscript by laying out their vision of how best to move forward with research in schizophrenia and other neuropsychiatric diseases. Their proposal, set forth in a policy piece in the March 25 issue of Science, calls for a $2 billion international effort over the next 10 years, with half to go to sequencing 100,000 complete personal genomes and half to be used to integrate genomic findings with neurobiology.
No one would argue that a significant influx of research funds earmarked for neuropsychiatric disease is warranted. As lead author Huda Akil, University of Michigan, Ann Arbor, and her colleagues point out, the top three diseases (schizophrenia, depression, and autism) add up to the leading cause of disability in North America and Europe, with the cost in lost earnings estimated at $200 billion per year in the U.S. alone. Yet there have been no major advances in prevention or treatment in 20 years or more.
The lack of results stems partly from the complexity of the problem. Schizophrenia and other neuropsychiatric disorders result from disruption of neural circuits, Akil and colleagues write, but because the development and function of circuits is so complicated, there are likely many routes to disease. That leads Akil and colleagues to call for a turn away from approaches like genomewide association. “Starting from a diagnosis and searching broadly for genetic causes that are commonly shared across all affected individuals is not likely to succeed....” they write. Instead, they espouse an approach of whole-genome sequencing that can detect private mutations and take into account the genetic and neurobiological heterogeneity of these disorders. The National Institutes of Mental Health is already moving in that direction, funding some whole-genome sequencing for psychiatric disorders, but the vision of Akil and coauthors would dramatically escalate current efforts. (For more discussion on the pros and cons of this shift in focus, see SRF Genetic series, Part 4.)
The second billion-dollar project, aimed at the integration of genetics with the latest techniques for studying circuit function in humans and in experimental animal models, seems less clear-cut than the genomic goal. An important component appears to be the production of animal models based on yet-to-be-discovered human genes.
The article gives the views of eight individuals. Now we would like to hear what the rest of you think. What is there to like about this proposal? What possible pitfalls do you as researchers and SRF readers see?—Pat McCaffrey.
Akil H, Brenner S, Kandel E, Kendler KS, King MC, Scolnick E, Watson JD, Zoghbi HY. The future of psychiatric research: genomes and neural circuits. Science. 2010 Mar 26;327(5973):1580-1. Abstract