(CNN) — For some people with depression, finding the right medication can be a trial-and-error process that lasts months or even years, which can worsen symptoms.
But what if doctors, when diagnosing someone with depression, could assess exactly how depression affects a patient’s brain and prescribe a treatment that gets it right the first time?
Scientists may be one step closer to that reality, thanks to new research that has identified six subtypes — or “biotypes” — of major depression using brain imaging combined with machine learning. The study, published Monday in the journal Nature Medicine, also tested how three of these biotypes responded to different antidepressants and treatments.
“There are no tests available that can help determine what type of depression (people) have, or, I think especially important, what treatment might be best for them,” said Dr. Leanne Williams, lead author of the study and Vincent VC. Woo 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 for the doctor or therapist to observe the symptoms and come up with a diagnosis.
About 280 million people worldwide and 26 million people in the United States have depression, which is the leading cause of disability. About 30% to 40% of people with depression do not experience improvement in symptoms after trying one treatment, according to the study. And about 30% of people diagnosed with depression experience treatment-resistant depression, when the disorder does not improve after multiple attempts at treatment.
“That’s what inspired this study — to have a whole new way to get the right treatment faster, to find the right treatment for each person the first time,” said Williams, who is also the director of the Stanford Center for Precision Mental Health and Well-Being. Williams lost her husband to a decade-long battle with depression in 2015, and for more than 20 years has focused on individualized mental health care.
Brain mapping of depression
The authors used data from 801 adult participants previously diagnosed with depression or anxiety and 137 healthy control participants. The authors used functional magnetic resonance imaging (MRI) to measure the participants’ brain activity while they were at rest doing nothing, focusing on brain regions already known to play a role in depression and on the connections between these regions. They also monitored brain activity as the participants, who were on average in their mid-30s, took part in various tests that assessed their cognitive and emotional functioning.
The authors also randomly assigned 250 participants to receive behavioral therapy or one of three common antidepressants: venlafaxine, escitalopram, or sertraline.
The six biotypes of depression the authors found include one characterized by hyperactivity in cognitive domains, which was associated with greater anxiety, negativity bias, dysregulated threat, and anhedonia than other biotypes. Disorder management refers to how people manage their responses to their fears, such as social interactions, Williams said. Anhedonia is a lack of interest in or enjoyment of life experiences.
Participants with this biotype also performed worse on executive tasks that measured how well they could control thoughts or behavior, make decisions or suppress distractions, Williams said. They also responded best to the antidepressant venlafaxine.
Another biotype was characterized by greater brain connectivity in three regions associated with depression and problem solving. Those with this biotype also made errors on executive tests but performed well on cognitive tasks. They found their symptoms reduced better with behavioral therapy, which teaches skills to better cope with everyday problems.
Higher connectivity in these brain regions may be what helped participants with this biotype to learn new skills, said study co-author Dr. Jun Ma in a press release.
There was also a phenotype characterized by reduced activity in the brain circuit that controls attention. This biotype was associated with more failures in tasks requiring sustained attention and less potential for improvement with treatment. People with this biotype may need medication for the disorder first so they can get more treatment, said Ma, the Beth and George Vitoux professor of medicine at the University of Illinois at Chicago.
The authors also found a biotype characterized by high emotional responsiveness, meaning the brains of participants in this group were more affected by emotional inputs such as their own feelings or people’s facial expressions, Williams said. One other phenotype was associated with less activity in cognitive brain regions and less connectivity in emotional regions, meaning these participants had difficulty responding to cognitive information and managing negative emotions.
Those last two biotypes did not respond to the drugs or therapy, suggesting that other options may be needed for people with these types, Williams said. “In other studies, we’re finding that they respond to some of the newer treatments that are being developed.”
The sixth biomarker identified was not different from a brain scan of the same region in people without depression. Williams said he thinks this finding may mean that the entire area of ​​brain biology that underlies depression has not been fully discovered.
“Depression is very diverse with many different causes, biological changes and treatments,” said Dr. Richard Keefe, professor emeritus of psychiatry and behavioral sciences at Duke University Medical Center in North Carolina, who was not involved in the study.
The study “takes a positive step toward” figuring these things out, Keefe added by email.
Obstacles and next steps
The study, while “sophisticated and very well done,” has several key problems, including how few people are enrolled in treatment, Dr. Jonathan Alpert, Dorothy and Marty Silverman Chair in Psychiatry and Behavioral Sciences at Montefiore. Clinic in New York City. “This has to be seen as a very preliminary study that needs to be repeated.”
In addition, more diverse samples are needed, said Alpert, who was not involved in the study and is a professor of psychiatry, neuroscience and pediatrics at the Albert Einstein College of Medicine. Most participants were white and 2% black.
But the most important next step is a study that tests the authors’ hypothesis — that if patients have specific biotypes, they will do better with a particular treatment — and follows participants over time, said Alpert, president of the American Psychiatric Association. Researches.
250 treatment participants were not randomized based on their biotypes. So, what Alpert recommends the authors do next is assign people to treatments based on their genotype and see if those participants have better outcomes with that method than if they had been assigned a treatment based on clinical judgment without knowing their genotype.
Another issue is that the study only investigated one form of psychotherapy and three medications; in the real world, there are many of each, Alpert said. The drugs were also all based on serotonin, but there are several other classes of antidepressants.
Research can only do so much at once, Alpert acknowledged, but incrementally addressing these shortcomings would help continue progress toward precision psychiatry.
What these results mean for you
The study’s methods and results are years away from being applied to direct patient care, experts said, but there is funding for such efforts.
“Since 2009, the National Institute of Mental Health has been invested in using basic science, including functional brain imaging as in this study, to identify the causes of mental illness using methods that dig deeper than traditional diagnostic methods,” Keefe said.
This month, Williams was awarded 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, which is about developing a better diagnostic and treatment tool for the biology of depression.
The new study’s method has begun to be piloted at a Stanford clinic, Williams said.
“When we use it in that setting, we can actually double the chance that someone will get better,” she said, taking the odds from about 30% of people improving with the traditional approach to about 75% with the more precise method.
This method is not intended to replace or be the primary option for evaluating individual cases of depression, Williams said. There is another piece that can be added to the puzzle that also includes information about symptoms, clinical interviews, and more.
For now, people with depression should know that “there is continued progress” toward getting patients effective treatment, Alpert said. If you are struggling, talk to a mental health professional about your options.
One powerful immediate effect these findings could have is reducing stigma, Williams said. For people who think their depression is just because they’re “not trying hard enough,” she added, understanding the disorder through the lens of objective measures of brain activity could be “very helpful.”
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