aAn experimental diagnostic tool in the form of a computer game can quickly identify people with depression based on anhedonia, a key feature of the disease, a new study shows.
Anhedonia, found in about 70% of people with major depressive disorder (MDD), is a loss of the ability to enjoy things that are normally pleasurable. The point at which people decide whether an activity brings them joy is known to change.
Published online on May 18th. Proceedings of the National Academy of Sciencesa new report describes a low-cost game that reliably identifies MDD patients in just 3 minutes. The game is based on neurobiological research, can be played remotely on a smartphone, and the study authors say its diagnostic accuracy is comparable to the best existing tests, which are typically used during multiple in-person clinic visits.
The new study, led by researchers at New York University Langone Health, found that people previously diagnosed with major depression using standard tests stopped enjoying key gaming activities 50 percent faster than healthy subjects.
“Our behavioral game gives us clues about what’s going on in the brains of people with depression. The hope is that this will allow researchers to identify patients as reliably as detecting heart disease by measuring blood pressure. ” said co-senior study author Paul W. Glimcher, Ph.D., chair of the Department of Neuroscience at New York University’s Grossman School of Medicine and director of the Translational Neuroscience Institute.
decision point
A groundbreaking theory dating back several decades claims that the pleasant or unpleasant nature of something (a reinforcer) depends on a person’s expectations. For example, if food is not expected, a single slice of pizza may be positively reinforced (enjoyable).
Dr. Glimcher explains how the gameplay simulates how people with depression experience joy in the world at large.
The findings argue that, at least in the majority of patients, MDD pathologically disrupts a person’s expectations and shifts the reference point for determining whether something is pleasant or not. This change causes activities that would be positive reinforcement for healthy people to feel negative. This behavioral game takes advantage of important research that first linked anhedonia to the anterior cingulate cortex, the brain region where such expectations are thought to be set.
Researchers asked 120 game players (50 diagnosed with major depression and 70 without) to compete to collect the most apples falling from a digital tree. Researchers perform this type of foraging task because evolution has hardwired reward-seeking circuitry into mammalian brains, especially when it comes to things that resemble food.
When players encountered a tree, the number of apples they foraged for each time they harvested decreased, and the researchers tracked when each player gave up on the tree and moved on to the next one. This game measures the point at which participants no longer find the tree’s yield of apples rewarding. On average, healthy people did not leave the tree until the yield had dropped to five apples, but MDD patients typically left the tree much earlier (before the yield had dropped to eight or nine apples, depending on the severity of depression). This is a nearly 50% increase in decision criteria.
The second research activity asked participants to bid on snacks and sought to measure how decision-making reference points respond to changes in the environment (e.g., changes in choices). Previous research has shown that when healthy people are asked to rate how much they are willing to pay for each snack in a previously presented small group of favorites (high values), and then asked to bid on a larger group of random snack foods (low values), their reference points rise, their bids fall, and all items in the random list are considered temporarily less valuable.
After healthy participants bid on favorites and several rounds of bidding against random snack lists, these reference points returned to the level they were at before participants bid on favorites. In contrast, the researchers found that MDD patients’ reference points did not return to their original settings even after the same sequence.
“Depressed patients seem unable to successfully adapt their expectations in response to changing conditions. This gives us a hint as to what is wrong mechanistically in their brains,” said Ardis Vittala, an MD/PhD student in Glimcher’s lab and co-lead author of the study. “For us, this looks like a therapeutic goal. We’re already looking to see if we can modify the stickiness of this reference point with behavioral therapy and drugs.”
“Depression is increasingly considered to be an umbrella term that includes several different symptoms,” added co-senior author Dan Iosifescu, MD, professor of psychiatry at New York University Grossman School of Medicine. “Measuring reference points could help us identify the specific subtypes of depression associated with anhedonia, reveal the brain computations that drive the disease, and tailor treatments. We might also be able to do this remotely by asking patients to play a smartphone game for a few minutes a week, rather than making multiple in-person visits. This would allow us to quickly adjust treatments.”
In addition to Dr. Glimcher and Dr. Iosifescu, study authors from the Translational Neuroscience Institute were co-first study authors Lulu Wu and Donni Yang. Dr. David Liebers; Elizabeth Tell. Song Xiaotong. Damon Dashti; Kenway Louie, MD; and Dr. Candice M. Laio. This study was funded by National Institute of Mental Health grant R21MH126197.
About NYU Langone Health
NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a focus on quality, resulting in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 among 118 comprehensive academic medical centers in the United States for the fourth consecutive year. US News & World Report was recently ranked No. 1 in the nation in four clinical specialties. NYU Langone provides comprehensive medical services with one high-quality treatment at seven inpatient facilities, Perlmutter Cancer Center, and more than 320 outpatient facilities in the New York region and Florida. The system also includes two tuition-free medical schools in Manhattan and Long Island and a large research enterprise.
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Greg Williams
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