“There are currently no tests available to help determine what type of depression (people) have or, I think particularly importantly, what treatment might be most appropriate for them,” said Dr Leanne Williams, senior 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 arrive at a diagnosis.”
About 280 million people worldwide and 26 million people in the United States have depression, which is the leading cause of disability. According to the study, about 30 percent to 40 percent of people with depression do not experience improvement in symptoms after trying a treatment. And about 30 percent of people diagnosed with depression go on to experience treatment-resistant depression when the disorder doesn’t improve after multiple treatment attempts.
“That’s what motivated this study — to have a whole new way to get the right treatment faster, to find the right treatment for every person the first time,” said Williams, who is also the director of the Stanford Center for Health Precise Mind. and wellness. Williams lost her partner to a long battle with depression in 2015, and for more than 20 years has focused her work on individualized mental health care.
Brain mapping of depression
The authors used data from 801 adult participants who had previously been diagnosed with depression or anxiety, and 137 healthy control participants. The authors used functional MRI — magnetic resonance imaging — to measure the participants’ brain activity while they were at rest and doing nothing, focusing on brain regions already known to play a role in depression and the connections between those regions. . They also monitored brain activity as the participants, who were in their 30s on average, took part in various tests that assessed their cognitive and emotional functioning.
The authors also randomly assigned 250 of the participants to receive behavioral therapy or one of three commonly used antidepressants: venlafaxine, escitalopram, or sertraline.
The six depression biotypes the authors found included one characterized by hyperactivity in cognitive regions, which was associated with more anxiety, negativity bias, threat dysregulation, and anhedonia than the other biotypes. Threat dysregulation refers to how people manage their reactions to their fears, such as social interactions, Williams said. Anhedonia is the lack of interest or enjoyment of life experiences.
Participants with this biotype also performed worse on executive function tasks that assessed how well they could manage thoughts or behaviors, make decisions or suppress distraction, Williams said. They also had the best response to the antidepressant venlafaxine.
Another biotype was marked by higher levels of brain connectivity in three regions associated with depression and problem solving. Those with this biotype also made errors on tests of executive function, but did well on cognitive tasks. They found that their symptoms were better relieved by behavioral talk therapy, which teaches skills to better deal with everyday problems.
Higher connectivity in these brain regions may be what helped participants with that biotype more easily adopt new skills, study co-author Dr. Jun Ma said in a press release.
There was also a biotype that was distinguished by lower levels of activity in the brain circuit that manages attention. This biotype was associated with more errors on tasks requiring sustained attention and less chance of improvement with therapy. People with this biotype may first need medication for the dysfunction in order to benefit more from therapy, said Ma, the Beth and George Vitoux Professor of Medicine at the University of Illinois Chicago.
The authors also found a biotype 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 lower activity in cognitive brain regions and less connectivity in emotional regions, meaning these participants had difficulty responding to cognitive information and regulating negative emotions.
Those latter two biotypes did not respond to medications or therapy, suggesting that other options may be needed for people with those types, Williams said. “In other studies, we’re finding that they respond to some of the newer treatments that are being developed.”
The sixth biotype identified did not differ from brain scans of the same region in people without depression. Williams said she thinks this finding may mean that the full range of brain biology underlying depression has not been fully discovered.
“Depression is many different things with many causes, biological changes and different 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. study. .
The study “takes a positive step in the direction” of figuring these things out, Keefe added via email.
Obstacles and next steps
The study, while “sophisticated and very well done,” has several major problems, including the low number of people enrolled in treatment, said Dr. Jonathan Alpert, the Dorothy and Marty Silverman chair of Montefiore’s department of psychiatry and behavioral sciences. Medical. Center in New York City. “It should be thought of 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 of the participants were white and 2 percent 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 follows participants over time, said Alpert, chairman of the Society’s Council. American Psychiatric Research.
The 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 biotypes and see if those participants do better by that method than if they had been assigned to a treatment based on uninformed clinical judgment. for their biotype.
Another issue is that the study only investigated one form of psychotherapy and three medications; in the real world, there’s a lot of each, Alpert said. The drugs were also all serotonin-based, but there are several other classes of antidepressants.
Studies can only do so much at a time, Alpert acknowledged, but addressing these gaps incrementally would help continue advances toward precision psychiatry.
What do these findings mean for you?
The study’s methods and findings 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 through approaches that go deeper than traditional diagnostic approaches,” said Keefe.
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 focused on developing a better diagnostic and treatment tool for depression biotypes.
The new study’s approach has begun to be applied experimentally at a Stanford clinic, Williams said.
“When we use it in that setting, we can effectively double the chance that someone will get better,” she said, taking the odds from about 30 percent of people getting better with the traditional approach to about 75 percent with the more advanced method. correctly.
This method is not intended to replace or be the primary choice for evaluations of individual cases of depression, Williams said. It’s another piece that can be added to the puzzle that also includes symptom information, clinical interviews, and more.
For now, people with depression should know that “continual progress is being made” toward efficiently getting patients into effective treatment, Alpert said. If you’re struggling, talk to a mental health professional about your options.
One powerful effect these findings could have immediately is reducing stigma, Williams said. For people who think their depression is just because they “don’t try hard enough,” she added, understanding the disorder through the lens of objective measures of brain function can be “profoundly helpful.”
– CNN
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