Stanford University study identifies six types of depression

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For some People with depressionFinding the right medication can be a trial-and-error process that takes months, or even years, and can make symptoms worse.

However, the doctor Diagnosing depressioncan we accurately assess how depression is affecting a patient's brain and prescribe the right treatment the first time?

Scientists may be one step closer to that reality, with a new study combining brain imaging and machine learning to identify six subtypes, or biotypes, of depression. Nature Medicinealso tested how three of these biotypes responded to various antidepressants and treatments.

“Currently, there are no tests that can help us identify what type of depression[people]have and, importantly, what treatment would be best for them,” said Dr. Leanne Williams, the Vincent V. C. Wu Professor of Psychiatry and Behavioral Sciences at the Stanford University School of Medicine in California and lead author of the study. “Currently, we rely on patients to tell us what they're experiencing and for doctors or therapists to observe symptoms and make a diagnosis.”

about 280 million In the world 26 million Approximately 30% of Americans suffer from depression, making it a leading cause of disability. Research shows that approximately 30% to 40% of people with depression do not see improvement after one treatment attempt, and approximately 30% of people diagnosed with depression will continue to experience depression in the future. Treatment-resistant depression If the disorder does not improve after multiple treatment attempts.

“That was the motivation for this study: to find a whole new way to get people to the right treatment sooner and find the right treatment for each person for the first time,” said Williams, who is also director of the Stanford Center for Precision Mental Health & Wellness. In 2015, Williams lost his partner to a decades-long battle with depression; She is focused on her work About personalized mental health care.

The authors used data from 801 adult participants who had been diagnosed with a depression or anxiety disorder, and 137 healthy control participants. They used functional MRI (magnetic resonance imaging) to measure brain activity while participants were at rest, focusing on brain regions already known to be involved in depression and the connections between those regions. They also monitored brain activity while participants, whose average age was in their mid-30s, completed a range of tests assessing cognitive and emotional functioning.

The authors also randomly assigned 250 of the participants to receive either behavioral therapy or one of three commonly used antidepressants: venlafaxine, escitalopram, or sertraline.

The six biotypes of depression the authors found included one characterized by overactivity in cognitive domains that was associated with more anxiety, negativity bias, threat dysregulation, and anhedonia than other biotypes. Threat dysregulation refers to the way people manage their responses to fearful things, such as social interactions, Williams said. Anhedonia is Lack of interest Or the enjoyment of life experiences.

Participants with this biotype also performed worse on executive function tasks that measure how well a person manages their thoughts and actions, makes decisions, and suppresses distractions, Williams said. They also responded best to the antidepressant venlafaxine.

The other biotype showed higher levels of connectivity in three brain regions associated with depression and problem solving. People with this biotype made mistakes on executive function tests but performed better on cognitive tasks. They found that their symptoms were better alleviated by behavioral therapy that taught them skills to better deal with everyday problems.

Higher connectivity in these brain regions may have helped participants with that biotype learn new skills more easily, said study co-author Dr. Jun Ma. In a news release.

Another biotype was characterized by lower levels of activity in the brain circuits that manage attention. This biotype was associated with making more errors on tasks requiring sustained attention and being less likely to improve with treatment. People with this biotype may need to first try medications to target their impairment in order to get more benefit from treatment, said Ma, the Beth and George Vito Professor of Medicine at the University of Illinois at Chicago.

The authors also found a biotype with high emotional reactivity, meaning that this group of participants' brains were more susceptible to emotional inputs, such as their own emotions and the facial expressions of others, Williams said. The other biotype was associated with lower activity in cognitive brain regions and less connectivity in emotional regions, meaning that these participants had difficulty responding to cognitive information and regulating negative emotions.

Williams said the last two biotypes did not respond to drugs or treatments, suggesting other options may be needed for patients with these types, “but other studies have shown that they respond to some of the newer treatments that are being developed.”

The sixth biotype identified was no different from brain scans of the same region in people without depression, a finding that Williams believes may mean the full extent of the brain biology underlying depression is still unknown.

“Depression has a wide variety of 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.

Keefe added in an email that the study “takes a positive step in the direction” of clarifying these issues.

Hurdles and next steps

The study is “elegant and very well done,” but has some important problems, including the small number of people who participated in the treatment, said Dr. Jonathan Alpert, the Dorothy and Marty Silverman chairman of psychiatry and behavioral sciences at Montefiore Medical Center in New York City. “This needs to be considered a very preliminary study that needs to be replicated.”

And more diverse samples are needed, said Alpert, a professor of psychiatry, neuroscience and pediatrics at Albert Einstein College of Medicine, who was not involved in the study. Most of the participants were white and 2% were black.

But the most important next step is a study that tests the authors' hypothesis that patients do better with certain treatments if they have a particular biotype and follows participants over time, said Alpert, who is chair of the American Psychiatric Association's Research Council.

The 250 treatment participants were not randomized based on biotype, so Alpert next urges the authors to assign people to treatments based on biotype to see whether this leads to better outcomes for participants than if they were assigned treatments based on clinical judgment without knowing the biotype.

Another problem is that the study looked at only one type of psychotherapy and three types of medications — in the real world, there are many of each, Alpert said. The medications were all serotonin-based, but there are several other types of antidepressants.

Alpert acknowledged that research is limited in what it can do at once, but addressing these shortcomings incrementally will help continue progress toward precision psychiatry.

Experts say it will be years before the research methods and results can be applied to direct patient care, but funding for such efforts is in place.

“Since 2009, the National Institute of Mental Health has been committed to using basic science, including functional brain imaging studies like this one, to identify the causes of mental illness through approaches that dig deeper than traditional diagnostic approaches,” Keefe said.

this month, Williams won the award An $18.8 million grant has been awarded as part of the National Institutes of Health's “Individually Measured Phenotypes to Advancing Computational Translation in Mental Health” initiative. The grant will support a five-year, 4,500-participant project centered on developing better diagnostic and treatment tools for depression biotypes.

The new research approach is beginning to be piloted at Stanford University's clinic, Williams said.

“Treating it this way essentially doubles the chances of improvement,” she said, noting that while traditional treatments give people about a 30% chance of improvement, the more precise treatments increase that to about 75%.

Williams said the method isn't intended to be a replacement or first-line method for assessing individual cases of depression — it's just another piece that can be added to a puzzle that also includes symptom information, clinical interviews and more.

For now, Alpert said people with depression should know that there are “continued advances” being made to more efficiently deliver effective treatment to patients. If you're suffering, Talk to a mental health professional About options.

Williams said one powerful immediate effect these findings could have is reducing stigma: For people who believe depression is due to simply “not trying hard enough,” understanding the disorder through the lens of objective measures of brain function could be “really helpful,” she added.