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'Holy moly, that is a slow burn': Research center in Boston aims to jump-start precision psychiatry

Sigmund Freud, father of psychoanalysis, poses for sculptor Oscar Nemon, 1931, in Vienna. (AP Photo)
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Sigmund Freud, father of psychoanalysis, poses for sculptor Oscar Nemon, 1931, in Vienna.

The science of precision medicine has made leaps in the past couple decades. It helps doctors use genetics and other data to figure out how to treat individual patients in a number of diseases, such as cancer and cystic fibrosis.

But one exception is mental illness.

A group of researchers based in Massachusetts is hoping to change that.

Jehannine Austin suffers from anxiety and depression, and as someone who works in health care — as a genetic counselor — they are open to a range of treatments.

“I've spoken to so many people over the years who have said, 'Oh, well, you know, mindfulness meditation or whatever really works for me,'” said Austin.

So Austin, who uses they pronouns, went to a class on meditation. But with all the quiet time sitting cross-legged, breathing deeply and marinating in their own thoughts, “basically I ended up having a panic attack,” Austin said.

Clearly, they would have to try another approach — perhaps medication, perhaps talk therapy — and it could take a while to find it.

This is the sort of trial and error that makes up the backbone of the psychiatric profession, and yet many in the field say that shouldn’t still be the case.

For more than a decade, researchers have been pursuing what’s called precision — or personalized — psychiatry.

“The basis of precision medicine is leveraging individual differences in our genes and biology and lifestyle and environment to improve diagnosis and treatment and prevention,” said Harvard University's Dr. Jordan Smoller, a leader in the field.

But even Smoller said the field of precision psychiatry is still nascent — a view held by many others.

“I think we're not where we are for oncology, infectious disease, maybe cardiovascular medicine,” said Dr. Tom Insel, former head of the National Institute on Mental Health and now an entrepreneur. “But we’re making progress.”

Last month, at a virtual conference, Insel said precision psychiatry could help address the current crisis in mental health — eventually.

“But holy moly, that is a slow burn,” Insel said. “And it doesn't really respond to the urgency that so many people are now feeling, especially through the pandemic.”

As one way to jumpstart the research, Smoller and others have launched the Center for Precision Psychiatry at Massachusetts General Hospital in Boston, which sponsored the conference.

Some of the center’s work focuses on genetics, and some on brain imaging, large data sets — even some animal models.

One goal is to develop new drugs to treat psychiatric disorders, as the field is still using medications that went on the market decades ago.

But scientists say the complex nature of mental illness — including the elusiveness of clear biomarkers — has made that goal tricky.

“There are thousands of (gene) variations,” Smoller said. “There isn't a single gene for one thing.”

Smoller said researchers have begun to pinpoint gene combinations for major disorders like schizophrenia and bipolar disorder, but “when it comes to the prospect of … clinical implementation, the progress has been somewhat slower.”

Scientists and pharmaceutical companies hope to develop genetic “risk scores” to help predict who will get sick as well as how an individual might react to a treatment — for instance, how the body metabolizes certain drugs.

Ideally, that would shrink the trial-and-error time spent on treatments that don’t work, avoid some side effects, and — in one of the most active areas of research — even help predict who is at greatest risk for attempting suicide.

But clinical trials to match genetic profiles with treatment have had mixed results and have not yet led to a new class of drugs.

Some scientists point out that pharmaceutical companies may be wary about precision psychiatry because narrowing down the pool of people likely to benefit from a drug could shrink their number of customers.

“Of course, the larger the population that you can treat with your drug, that usually the bigger the commercial opportunity,” said Dr. Morgan Sheng, a scientist for Cambridge-based Broad Institute, as well as a stakeholder in several pharmaceutical companies. “But … I'd much rather sacrifice the size of the population for a high level of efficacy in a smaller population.”

Sheng added that, “If you have a drug that is very efficacious, you can charge more for it compared with a drug that is less efficacious. So you can reap some benefit from precision medicine, even if you have a smaller population."

But, for now, using genetic profiles to just figure out who will develop severe mental illness is still difficult.

“The thing is, tests that we develop like that are never going to be entirely accurate,” said Austin, who also spoke at the conference. “There's too many variables in what leads to those outcomes then over and above just genetics.”

Those variables include sleep, nutrition, social support and stress management.

Austin, who’s based at the University of British Columbia, uses family history, more than genetic testing, to determine whether someone has inherited a risk of mental illness. But risk does not make the outcome inevitable.

“Could we end up in a situation where we've got genetic tests that say you're more likely to benefit from this or that? Yeah, yeah, probably,” Austin said. “But should that supersede other things like clinical judgment or common sense? No, maybe not. It's something to take into the bigger picture."

That’s what researchers with the new center in Boston say they’re trying to do — seeking mental health biomarkers, using artificial intelligence, and mining other data to move precision psychiatry forward — while acknowledging it has a ways to go.

Karen Brown is a radio and print journalist who focuses on health care, mental health, children’s issues, and other topics about the human condition. She has been a full-time radio reporter for NEPM since 1998.
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