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A Psychologist Is Trying to Use Genetics to Predict If Therapy Will Work

A London-based Thalia Eley hopes to find genetic factors that could help advise patients on the best psychological treatment for them.

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Jun 24 2016, 9:00am

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For anyone looking to access mental health care in the British National Health Service, choosing a type of therapy or other treatment can be a daunting task. A quick perusal of the handy guidebook "Which Talking Therapy for Depression," offers up Cognitive Behavioral Therapy (CBT), Interpersonal Therapy (IPT), and Brief Dynamic Interpersonal Therapy (BDIPT), either one-on-one, in a group, or even by remote, computer-based treatment, and that's if talk therapy is even right for you in the first place.

But help may be on the way. A group of scientists at King's College London's Institute of Psychiatry are currently hard at work on a way to match prospective patients with the method most likely to help them—and all the patient has to do is spit in a tube and have their genes tested.

"How treatment is allocated is still relatively random," said Dr Thalia Eley, professor of developmental behavioural genetics, and one of the lead scientists of the project. "We want to find a way to identify from the outset which treatment type is going to be best suited for a specific individual."

Just like a doctor can recommend a specific diet to a person genetically predisposed to heart disease, psychological treatment could be more personalized

Eley thinks there is a way to predict whether a person will respond to a given treatment, and it's as personalized as you can get: Her team will be gathering genetic samples from people who have used the NHS program for CBT, and testing their genome against their therapeutic result.

They're betting that the latest genetic screening technology is sufficiently advanced to find genetic differences that could predict how people will respond to treatment. And then, just like a doctor can recommend a specific diet to a person genetically predisposed to heart disease, psychological treatment could be more personalized.

But is something as complex as talking to a therapist reducible to genes?

"There's a philosophical sense that it's not plausible" said Eley. "But twin studies show us that at least some environmental response is heritable."

Eley and other researchers have worked with twins for decades, trying to tease out what about the identical pairs could be predicted based on their shared genes. Large scale twin studies have shown that conditions like severe depression are at least partly heritable—meaning that genes are one of many factors that can influence these conditions—but scientists have struggled to connect that influence with specific genes.

The problem is that most psychological conditions won't be linked to a single gene, or even a few, but tens or hundreds each making a small contribution. While diseases like Huntington's are relatively simple to detect (a doctor examines a single gene for the mutation, and if it's present there's a good chance the disease symptoms will occur), a recent study of schizophrenia showed that there were over 100 genetic factors that predicted whether a person would be affected.

Something as complex as therapy response won't come down to a single gene

"The findings from psychiatric genetics and from complex genetics research more broadly suggest that the single candidate gene approach doesn't usually work," said Dr Laramie Duncan, a genetics researcher at Stanford University. She said that researchers have to test tens of thousands of people and millions of genetic variants.

I asked her if she thought it was possible to find a genetic link regarding response to a treatment like therapy. "Yes, I think almost certainly it will happen in time. You just need a sufficiently large sample size to find the specific genetic causes," she said. Scale is everything.

Eley is hoping the NHS can provide that scale. Her group previously attempted to find a genetic link with the outcome of CBT for children with anxiety disorders by studying both single genes and genome-wide scans, but the studies looked at fewer than a thousand patients and didn't find a significant link.

Fortunately, for the past eight years the NHS has been running a program to promote better access to psychological therapy. Since it began, some one million people have taken the offer up.

That means the group has access to hundreds of thousands of people who recently completed CBT; any patients who agreed to be contacted for later research are potential genetic donors.

For the moment, Eley is piloting the program—requesting saliva samples through the mail—in South London, where she works. But she hopes to take the search nationwide within a few years, eventually collecting tens of thousands of samples.

That kind of spread is much more diverse than a typical clinical trial, but all of the noise is part of the point for Eley.

"With this program there'll be many kinds of treatment, many different problems—but if our results aren't able to rise above the noise in the everyday care system, they won't be useful in the everyday care system," she said.

To sift through all the data, the genotyping is all done in-house on a platform that can process thousands of samples per month. Each sample is linked to the clinical record of the person who submitted it (the records are anonymized) so the team can compare the genotypes of people who responded well or less well to different types of treatment. Something as complex as therapy response won't come down to a single gene—they've learned that already—but the group can now test for over 500,000 known genetic variants. Eventually, they think they'll be able to find genetic factors that influence response.

Overall, Eley said that she's not interested in showing how or why therapy works through genetics, or even which factors are involved. "I'm not a biologist. I'm quite happy for other people who identify genes of interest from my work and move forward with them," she said.

She envisions something more useful for the average person: The ability to tell people what the chances are that a certain therapy might work for them, the same way you might recommend a treatment based on someone's age or personal history.