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For some People suffering from depressionFinding the right medication can be a process of trial and error lasting months or years, which can make symptoms worse.
But what if the doctor, Describe someone as depressedIs it possible that we can assess how depression is affecting a patient’s brain, and recommend a treatment that works right the first time?
Scientists may be one step closer to this reality, thanks to new research that has identified six subtypes — or “biotypes” — of major depression through brain imaging combined with machine learning. The study, published Monday Journal Nature Medicinealso tested how three of those biotypes responded to different antidepressant drugs and treatments.
“There are currently no tests available that can diagnose what type of depression (people) have, or, I think more importantly, what treatments might be most appropriate for them,” said Dr. Leanne Williams, the study’s senior author and the Vincent V.C. Wu Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine in California. “The current situation is that we rely on a person to tell us what they are experiencing and a physician or therapist arrives at a diagnosis by observing the symptoms.”
About this 280 million people around the world and 26 million people There has been an increase in the number of people suffering from depression in the United States, which is a leading cause of disability. According to studies, about 30% to 40% of people with depression experience no improvement in symptoms even after trying a treatment. And about 30% of people with depression experience further depression Treatment-Resistant Depression When the disorder does not improve after several treatment attempts.
“That’s what inspired this study — to find a new way to get the right treatment as quickly as possible, to find the right treatment for each person the first time,” said Williams, director of the Stanford Center for Precision Mental Health and Wellness. Williams lost her partner in 2015 to a decades-long struggle with depression and has been a partner for more than 20 years. He has focused his work On personalized mental health care.
The authors used data from 801 adult participants who had previously been diagnosed with depression or anxiety, and from 137 healthy control group participants. The authors used functional MRI – magnetic resonance imaging – to measure participants’ brain activity when they were at rest, doing nothing, focusing on areas of the brain already known to play a role in depression, and on the connections between those areas. They also monitored brain activity when the participants, who were on average in their mid-30s, engaged in various tests that assessed their cognitive and emotional functioning.
The authors randomly assigned 250 participants to receive behavioral talk therapy or one of three commonly used antidepressant medications — venlafaxine, escitalopram or sertraline.
Of the six biotypes of depression the authors found, one characterized by hyperactivity in cognitive areas was associated with greater anxiety, negative bias, threat regulation and anhedonia than the other biotypes. Williams said threat regulation refers to how people manage their responses to their fears, such as social interactions. Anhedonia is what is responsible for depression. lack of interest in Or enjoy life’s experiences.
Participants with this biotype also performed worse on executive function tasks, which assess how well they can manage thoughts or behaviors, make decisions or suppress distraction, Williams said. They also had the best response to the antidepressant venlafaxine.
Another biotype was found to have higher levels of brain connectivity in three regions associated with depression and problem-solving. People with this biotype also made mistakes on executive function tests, but performed well on cognitive tasks. They found that their symptoms were better improved by behavioral talk therapy, which teaches skills to better address daily problems.
Study co-author Dr. Jun Ma said that higher connectivity in these brain areas may have made it easier for participants with this biotype to adopt new skills. in a news release,
There was also a biotype that was characterized by a low level of activity in brain circuits that manage attention. This biotype was linked to more mistakes in tasks requiring sustained attention, and was less likely to improve with treatment. People with this biotype may need medication for procrastination earlier so they can benefit more from treatment, said Ma, the Beth and George Vitaux Professor of Medicine at the University of Illinois Chicago.
The authors also found a biotype that was characterized by high emotional reactivity, meaning the brains of participants in this group were more affected by emotional input such as their own emotions or people’s facial expressions, Williams said. Another biotype was associated with less activity in cognitive brain regions and less connectivity in emotional regions, meaning these participants had difficulty reacting to cognitive information and regulating negative emotions.
Those last two biotypes did not respond to drugs or therapy, Williams said, which suggests other options may be needed for people with those types. “In other studies, we are finding that they do respond to some of the newer treatments that are being developed.”
The sixth biotype identified showed no difference from scans of the same brain region from people without depression. Williams said he thinks this finding could mean that the full range of brain biology behind depression hasn’t been discovered.
“Depression is many different things, with many different causes, biological changes and treatments,” said Dr. Richard Keefe, emeritus professor of psychiatry and behavioral sciences at Duke University Medical Center in North Carolina, who was not involved in the study.
This study is a positive step toward knowing these things, Keefe said via email.
Obstacles and next steps
Dr. Jonathan Alpert, the Dorothy and Marty Silverman Chair in the Department of Psychiatry and Behavioral Sciences at Montefiore Medical Center in New York City, said that while the study is “sophisticated and very well done,” it has several major problems, including the small number of people enrolled in treatment. “It should be thought of as a very preliminary study that should be replicated.”
In addition, more diverse samples are needed, said Alpert, who was not involved in the study and is a professor of psychiatry, neurology and pediatrics at Albert Einstein College of Medicine. Most participants were white, and 2% were black.
But the most important next step is a study that tests the authors’ hypothesis — that if patients have particular biotypes, they will do better on a specific treatment — and tracks participants over time, said Alpert, chairman of the American Psychiatric Association’s Research Council.
The 250 treatment participants were not randomized based on their biotype. So, what Alpert suggests to the authors next is to give people treatments based on their biotype and see if those participants get better outcomes with that approach than they would have if they were given treatments based on clinical judgment without knowledge of their biotype.
Another issue is that the study examined only one form of psychotherapy and three medications; in the real world, there are many types of medications, Alpert said. The medications were also all serotonin-based, but there are a few other classes of antidepressants as well.
Alpert acknowledged that studies can only do so much at a time, but gradually addressing these shortcomings will help continue the progress toward precision psychiatry.
It will take years for the study’s methods and findings to be applied in direct patient care, but funding is available for such efforts, experts said.
“Since 2009, the National Institute of Mental Health has been engaged in using basic science, including functional brain imaging in this study, to identify the causes of mental illness by probing more deeply than traditional diagnostic approaches,” Keefe said.
this month, Williams honored An $18.8 million grant as part of the National Institutes of Health’s Individually Measured Phenotypes to Advance Computational Translation in Mental Health initiative. The grant supports a five-year project involving 4,500 participants, focused on the development of improved diagnostic and treatment tools for depression biotypes.
The new study’s approach has begun to be applied experimentally at the Stanford clinic, Williams said.
He said, “When we use it in that situation, we can double the chance of a person getting better.” He said that while the probability of people getting better with the traditional method was 30%, the probability of people getting better with the more accurate method has reached 75%.
Williams said this method is not intended to replace or be the primary option for assessing individual cases of depression. It is another piece that can be added to the puzzle that includes symptom information, clinical interviews and more.
For now, people with depression should know that “there is constant progress” toward providing effective treatments to patients, Alpert said. If you’re struggling, Talk to a mental health professional Explain your options.
Williams said one powerful impact of these findings could be to reduce immediate stigma. For people who think their depression is simply because they “didn’t try hard enough,” understanding the disorder through the lens of objective measures of brain function could be “very helpful,” she said.
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