‘Software instead of pills’: Video game developed at University of Utah to treat depression receives $7.5M grant

A University of Utah lab received a $7.5 million grant from the National Mental Health Institute to conduct clinical trials for Neurogrow — a video game designed to treat older adults with depression.

Neurogrow invites players to care for a virtual garden with changing demands and conditions — intended to target and strengthen circuits in the front of the brain in older adults who suffer from depression. The game is developed by the Therapeutic Games and Apps Lab at the U. based on research by Dr. Sarah Shizuko Morimoto, an associate professor in the Department of Population Health Sciences.

The $7.5 million grant will fund two clinical studies — one at the U. and one at the University of Connecticut. Researchers now face a critical testing period to further assess the efficacy of the game that will determine how it may be distributed in the future, including as a potential medical treatment.

Morimoto and her team received the grant in April and began the clinical trials in August. She said receiving the grant marked “the crowning achievement” of her career.

“We’re doing the work of medicine here,” said Roger Altizer, director of digital medicine at the Center for Medical Innovation. “And it just happens to be with software instead of with pills.”

On the first try

Morimoto has dedicated more than a decade to exploring how video games may revitalize damaged circuits in the frontal lobe that can block the effectiveness of antidepressant medication. She began working on the project in 2007 at the Weill Cornell Institute of Geriatric Psychiatry, run by Dr. George Alexopoulos, a top researcher in the field of geriatric depression.

Morimoto said that the recovery mechanism in the brain that helps people overcome depression can erode as they get older. Known as the “disuse atrophy hypothesis,” the degradation could be counteracted by targeting and rebuilding aging circuits.

Morimoto compared the circuits in the brain to a phone line. If the line is cut, it doesn’t matter how much signal boosting happens at either end of the phone call: The line needs to be repaired. Antidepressants can help to improve a patient’s mood, but without the proper cognitive infrastructure, the medication is ineffective.

“We’re kind of artificially coming in from the outside and making you work out these parts of the brain,” Morimoto said.

In an early clinical trial before Morimoto came to Utah, the game was tested against antidepressants with patients who hadn’t previously responded to medication. Between 60% to 70% of patients reported that the game provided at least some relief, Morimoto said. She ran another clinical trial, this time testing the game against a generally stimulating computer program, and found that 60% to 70% of patients reported a 50% reduction in their depression symptoms.

Morimoto approaches aging like a brain disease and takes a targeted approach to help people stay functional and enjoy the rest of their life.

“I hate it when people say. ‘Oh, I’m rejuvenating your brain,’ or, ‘We’re gonna make you young again’,” Morimoto said. “That isn’t what we’re doing at all. We are strengthening your ability to utilize these parts of your brain that have become less useful as you age.”

Morimoto was running another clinical trial at the U. when COVID-19 shutdowns began in March 2020. She stopped the trial to protect her patients and applied for the National Mental Health Institute grant using data obtained in that trial.

Typically, a prescription molecule or a psychotherapy treatment will be tested against a placebo and will remain exactly the same throughout a clinical trial, but Morimoto knew that Neurogrow would have to be updated often to treat people effectively.

“Asking research reviewers to accept that we’re saying, ‘Hey, we want to test the efficacy of this, but we’re not going to tell you exactly what it’s going to look like at the end’ — that’s a hard concept to get behind,” Morimoto said.

Morimoto wrote the request for the grant “from the heart,” against the advice of some researchers she knew. In medical research, it’s common for grant providers to ask researchers to update their methodology upon their first request for funding, Morimoto said. The National Mental Health Institute approved Morimoto’s request for the five-year grant on her first attempt.

“We got it on the first try, which was extremely exciting, and also scary,” Morimoto said.

Morimoto received the news in October of 2020 and is working with the University of Connecticut to conduct the trial at two sites, which means she will not be able oversee day-to-day operations at one site — an important test for how effective Neurogrow can treat patients on its own.

“For me, it’s anxiety. Constant anxiety, because, you know, it’s my baby,” Morimoto said.

One of the most difficult parts of implementing the program has been training workers to adequately explain how the game works to patients who have never touched a video game before.

The trial at the University of Connecticut is being conducted by Dr. David Steffens, the chair of the School of Medicine’s Department of Psychiatry, who Morimoto called a world-renowned specialist in geriatric psychiatry. Morimoto met Steffens after receiving an American Academy of Geriatric Society award in 2008 during her time at Cornell, and he’s been a mentor for her over the years.

Morimoto hopes to one day administer the game at community clinics throughout the nation, but she said she wants to ensure that the game is empirically-proven to help patients before it is made available.

How the trial works

The trial in Utah is being conducted at the Huntsman Mental Health Institute, though patients can also participate remotely.

It begins with an initial cognitive test. Patients then undergo a six-week clinical trial where they play Neurogrow and other included games for about 30 hours over the course of four weeks.

After, patients take another cognitive test to see what, if anything, has changed. Trial administrators then make follow up calls for the following two weeks to see how patients are doing, followed by voluntary three-month and one-year follow ups for patients that want to be evaluated again.

Patients who play the game at the Huntsman Mental Health Institute are treated to “nice comfy chairs and snacks,” Morimoto said. Those who prefer to play remotely are given a tablet with the game installed on it and can Zoom with administrators while they play in case they have questions.

Morimoto hopes that at least 250 people will participate in the trial, but she noted that recruitment has been challenging. Any older adult who may be dealing with depression may call 801-746-9588 to be considered for the trial.

Previously, Morimoto only tested Neurogrow on patients who were taking medication to treat their depression, but this trial also will accommodate people who aren’t taking medication. Morimoto said her team will collaborate with a patient’s physician to track their progress and help them move forward after the trial ends.

“We really hope that we get as many people as possible to give this a shot,” Morimoto said. “And, you know, they really don’t have anything to lose. There’s really no side effects other than sometimes getting a little bit frustrated.”

The treatment is free for patients. In fact, patients are reimbursed for the time they spend playing the games and taking mood evaluation tests, which adds up to about $250 for all six weeks of the trial, Morimoto said.

She noted that her team is working with a language professor to translate the game into Spanish to reach more potential participants. The Spanish version of the game should be ready for testing within about six months.

“I would say the majority of apps for depression that are out there are not targeting the neurobiology of the illness,” Morimoto said. “They’re doing psychotherapy over the web or giving you cognitive or behavioral tools to use during your day ... What we’re doing is kind of a different a whole different ballgame.”

Morimoto said that most universities don’t have the resources to attempt to gain approval from the Food and Drug Administration to market a game as a medicinal treatment. She’s grateful that the University of Utah has been “a special place” to develop Neurogrow.

Games as a medical treatment could also offer huge savings for both patients and the health care system, Altizer said, noting that both he and Morimoto believe digital medicine “is going to be the future.”

“Wouldn’t it be great if your health care was fun?” Altizer said.