To improve mental health treatments, scientists try to dissect the pieces that make them work

Successful mental health treatments can function like a conversation: The brain hears some kind of message — whether it’s from a drug or another approach — and the brain responds in a way that alleviates some symptoms.

Scientists are listening in on those conversations — and trying to “back translate” them to figure out how successful treatments actually work. And that effort is about to get a big boost: The nonprofit Wellcome Trust recently announced a $200 million commitment to support more mental health research, including scientists studying the underpinnings of existing treatments.

“The money is to think about doing things in a different way,” said Andrew Welchman, who oversees neuroscience and mental health work at the Wellcome Trust. The goal isn’t just to understand why treatments work or fail — it’s also to figure out how to tap into those findings to make treatments more effective. Neuroscience experts say that’s direly needed.

“There’s absolutely no doubt about it. Our treatments don’t reach the number of people they need to,” said Emily Holmes, a clinical neuroscientist at Uppsala University in Sweden.

Many patients don’t respond to treatments. Many cycle through one treatment after another without any relief, hoping to eventually land on one that works. Others find treatments that work for them — but only for awhile. And scientists don’t fully know why that’s the case.

“Some of that is because [the treatments] have quite broad effects, and some it is because the studies haven’t been done,” said Dr. Leanne Williams, a Stanford neuroscientist and the founding director of the school’s Center for Precision Mental Health and Wellness.

The mechanisms that make a treatment work can happen in any number of ways, Holmes said. Back-translating is about figuring out those mechanisms — or the “magic ingredients,” as she calls them.

A drug or treatment might be effective because it produces changes in the brain. But it also might work because it drives other types of changes, like at a cognitive or behavioral level. One example: shifting someone’s cognitive bias. Studies show that when people are shown an ambiguous face, some people are prone to interpret it negatively, and others are inclined to interpret it positively. If a psychological treatment bumps a negative bias toward the center, it could produce downstream effects, like improving a person’s mood.

An example of that idea in action: the work of University of California, Los Angeles, neuroscientist Michelle Craske and her colleagues. They’ve worked to unpackage the mechanisms behind exposure therapy, a common treatment for anxiety disorders that involves repeated exposures to things that a person fears or avoids. It works for some people, but not everyone. Craske and her colleagues are hunting for ways to tweak the treatment’s mechanisms to make exposure therapy more effective.

“If you can back translate the successful treatments we have, it can allow you to ask questions about how to extract the essential ingredients and make them better,” said Holmes.

Williams does her own type of back-translating. Patients who come into Stanford’s precision psychiatry studies go through a battery of tests: They undergo genetic testing and functional MRI scans to capture images of their brain circuitry. They’re evaluated on emotional regulation. They’re quizzed about their symptoms and their quality of life. Then, after weeks of treatment with existing drugs or therapies, they do it all again to see what changed.

Williams and her colleagues use those measures to come up with more precise subtypes of depression and anxiety. They’re also testing whether they can achieve better outcomes when treatment is guided by that testing.

“The best way to reduce the impact of the illness is to get treatment right the first time,” Williams said.

Welchman of Wellcome said he hopes the investment will ultimately produce better treatments for the tens of millions of people across the globe with mental health conditions. The organization is additionally dedicating some of its funding to develop common standards for how anxiety and depression are evaluated, so it’s easier to compare data across different projects. Wellcome is also aiding efforts to create a sweeping database of mental health research that lets researchers mine for patterns.

The investment is still in the early planning stages. But in the meantime, experts are excited that back translation is gaining traction.

“The Wellcome investment comes at a brilliant time,” said Holmes. “The really exciting thing is to have lots of people asking questions in novel ways.”