Medical research usually takes much longer than expected. Sometimes there are quick payoffs, such as for AIDS, which only took about a decade. But Nixon’s War on Cancer is almost a half-century old, with modest progress (such as saving my life back in 1997). Brain health might turn out to be the most complicated subject of all.

Fr0m the NYT:

Mapping the Brain’s Genetic Landscape

Scientists have taken a step toward building a computer model of the brain’s genome, one that may help clarify the genetic roots of schizophrenia, autism and other disorders.

By Benedict Carey, Dec. 13, 2018

For the past two decades, scientists have been exploring the genetics of schizophrenia, autism and other brain disorders, looking for a path toward causation. If the biological roots of such ailments could be identified, treatments might follow, or at least tests that could reveal a person’s risk level.

In the 1990s, researchers focused on genes that might possibly be responsible for mental distress, but then hit a wall. Choosing so-called candidate genes up front proved to be fruitless. In the 2000s, using new techniques to sample the entire genome, scientists hit many walls: Hundreds of common gene variants seemed to contribute some risk, but no subset stood out.

Even considered together, all of those potential contributing genes — some 360 have been identified for schizophrenia — offered nothing close to a test for added risk. The inherited predisposition was real; but the intricate mechanisms by which all those genes somehow led to symptoms such as psychosis or mania were a complete mystery.

Now, using more advanced tools, brain scientists have begun to fill out the picture. In a series of 11 papers, published in Science and related journals, a consortium of researchers has produced the most richly detailed model of the brain’s genetic landscape to date, one that incorporates not only genes but also gene regulators, cellular data and developmental information across the human life span.

The work is a testament to how far brain biology has come, and how much further it has to go, toward producing anything of practical value to doctors or patients, experts said. …

The $50 million project, initiated in 2015 and financed by the National Institute of Mental Health, involves more than a dozen research centers and scores of specialists in cell biology, genetics and bioinformatics, the application of advanced computer learning to huge data sets. It is an all-hands, brute-force effort, coordinating top brain banks and brain scientists at major research centers, led by Yale, Mount Sinai, U.C.L.A. and the University of California, San Francisco.

The new model was based in part on analyses of nearly 2,000 human brains, from people with and without diagnoses, collected over decades. … This combined analysis improved predictive power to about 25 percent over random guessing, from 4 percent in previous models.

“One of the things that’s really interesting about psychiatric disease is that it’s more heritable than many other diseases,” Dr. Gerstein said. “But people don’t have any clue about mechanisms between the underlying gene variants” and the symptoms, for disorders such as schizophrenia or autism. “Now, we’re starting to fill that in.” …

For the time being, those hypotheses are unformed. And, for all the coordination and dazzling science on display, there is a long way to go before any practical payoff arrives, some experts said.