We Are Now At A Major Turning Point In Understanding Mental Illness

Mental illness is among the most crippling healthcare crises of our time - not only because it is one of the leading causes of disability worldwide, but because we still understand so little about how it works.

After years of almost stagnant psychopharmalogical research, though, two historic announcements by The Broad Institute on July 22 indicate that we may be at a turning point.

Researchers announced the largest-ever donation to psychiatric research ($650 million from Ted Stanley) and the publication of the largest-ever study of schizophrenia, an analysis of the genomes of 37,000 people with schizophrenia and 114,000 without.

The study, a collaboration between Broad Institute scientists and hundreds of others, identified 108 genes linked to schizophrenia, suggesting many entirely new, unexplored targets for treatment that may have widespread implications for the direction of research on other mental illnesses. The results were published July 22 in the journal Nature.

"The field of psychiatric disease research is at a critical point," said Stanley, the record-making donor, in a video accompanying the announcement. "It's now possible to begin to decode the biological basis of psychiatric disorders."

Most importantly, the finding - and the funding - may pave the way for research toward treatments that are based on science, not serendipity.

"We're poised for real advances here," said National Institutes of Health director Francis Collins, in a video accompanying the announcement. "I'm impatient. But that impatience is now being met with results."

The Sorry State of Mental Health Treatment

One in five American adults takes at least one psychiatric medication, but most of those compounds were discovered by accident. In many cases, scientists still lack even the most basic understanding of why certain pills work, in part because the diseases they target are still largely mysterious.

Take selective serotonin reuptake inhibitors - SSRIs sold under brand names like Prozac, Zoloft, and Paxil, which are prescribed in large numbers to treat depression and anxiety. They sometimes work, and they sometimes don't. In both cases, nobody is quite sure why.

"While S.S.R.I.s surely alter serotonin metabolism, those changes do not explain why the drugs work, nor do they explain why they have proven to be no more effective than placebos in clinical trials," Gary Greenberg, a psychotherapist, wrote in a New Yorker essay, The Psychiatric Drug Crisis. The complexity of the brain, he goes on to suggest, might make it "an elusive target for drugs."

Part of the problem with the misleading idea that a mental illness is no more than a chemical imbalance that needs to be corrected - just add a little more serotonin to the mix, for example - is that "the brain isn't a bowl of soup," Thomas Insel, the director of the National Institute for Mental Health, told MIT Technology Review. "It's a really complex network of networks."

By ordinary medical standards, psychiatric drugs are shamefully old-fashioned. They tend to treat symptoms instead of root causes, which in many cases remain elusive. For decades, real pharmacological innovation in this field - while so desperately needed - has seemed to be almost nonexistent.

"All of our current antidepressants, antipsychotics and anti-anxiety drugs share the same molecular targets in the brain as their prototypes from the 1950s," wrote Richard A. Friedman, a psychiatrist at Weill Cornell Medical College, in The New York Times. "With rare exceptions, it is hard to think of a single truly novel psychotropic drug that has emerged in the last 30 years."

Without a more nuanced understanding of what causes mental illness in the first place, it seemed that dismal trend was not likely to shift. That's precisely what makes the Broad Institute announcement so exciting.

A New Way Forward

The announcement doesn't suggest that we have won a battle against mental illness, which still remains mostly inscrutable. But it should open the floodgates for future research, leading the way in a very promising new direction.

"What this means is that the pharmaceutical companies who left this field because there was nothing concrete to work on are putting their toes back in the water," said Eric Lander, the director of the Broad Institute.

While the excitement around the announcement is warranted, caution is also necessary. The genomic analysis of people with schizophrenia is an important step, but it's also a preliminary one.

"A genetic test by itself will probably never be enough to make a diagnosis," said Steve McCarroll, the director of genetics at the Stanley Center for Psychiatric Research at the Broad Institute. It also is unlikely to lead to a simple cure.

Mental illness is complex, and scientists probably won't discover a single gene that causes any particular disorder. But genetic testing could be combined with brain imaging and cognitive testing to get a more complete picture of risk that could be used to intervene in mental illnesses early - perhaps even before symptoms emerge.

Genomic analysis might also suggest novel targets for drugs. The schizophrenia study, for example, confirmed earlier theories that the immune system seems to be involved in the disorder. That and similar findings might not lead to better treatments immediately, but the researchers are confident that it will eventually.

"We can't promise [a treatment] is going to be here today, this week, this year, or even this decade," said Lander. "But it's definitely going to happen.

"The momentum now is unstoppable."