Stanford Medicine Researchers Discovered A New Depression Subtype Known As The “Cognitive Biotype,” Which Doesn’t Respond Well To Commonly Prescribed Antidepressants

According to the National Institute of Mental Health (NIH), an estimated 21 million U.S. adults experienced at least one major depressive episode in 2021.
Despite the prevalence of depression across the country, though, there is no one-size-fits-all approach. A new groundbreaking study conducted by researchers at Stanford Medicine highlights this reality.
The study uncovered a new category of depression known as the “cognitive biotype,” which impacts 27% of depressed patients and cannot be successfully treated using commonly prescribed antidepressants.
Through cognitive tasks, the team discovered that patients with this biotype had difficulty displaying self-control, planning ahead, suppressing inappropriate behavior, and maintaining focus in the presence of distractions.
Brain imaging tests also revealed that the patients had decreased brain activity in two specific regions responsible for the successful completion of such tasks.
However, depression has been historically defined as a mood disorder, pushing doctors to prescribe antidepressants such as selective serotonin reuptake inhibitors (SSRIs) to target serotonin production. Yet, among patients with cognitive dysfunction, these drugs are much less effective.
The Stanford Medicine team conducted this study as part of a larger effort to pinpoint treatments that can target depression biotypes.
“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” said Leanne Williams, the study’s senior author.
“Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”

ID 167954611 – © Nenitorx – Dreamstime.com – illustrative purposes only, not the actual people
Just over 1,000 adults who were previously not medicated for major depressive disorder participated in the study. Each patient was randomly given one of three antidepressants that are widely prescribed.
The antidepressants included escitalopram or sertraline (brand names Lexapro and Zoloft, respectively), which target serotonin. The third antidepressant was venlafaxine-XR (brand named Effexor), which targets both serotonin and norepinephrine.
The patient pools’ depressive symptoms were measured both before and after receiving antidepressant treatment using two surveys. The first was clinician-administered; meanwhile, the second survey was a self-assessment. Changes in sleep, eating, social and occupational functioning, and quality of life were tracked.
Before and after treatment, each patient also completed various cognitive tests to gauge working memory, verbal memory, sustained attention, and decision speed.
Finally, prior to taking any medication, 96 patients underwent functional magnetic resonance imaging (fMRI) while engaging in a task known as “GoNoGo.” Essentially, this task requires the participants to press a button as rapidly as possible after they see the phrase “Go” in green. At the same time, they are not supposed to press the button when they see the phrase “NoGo” in red.
Neuronal activity was able to be tracked by measuring blood oxygen level changes, which revealed activity in different brain regions that correspond to “Go” or “NoGo” responses. Afterward, the team compared the participants’ scans against individuals who did not have depression.
This revealed that 27% of the participants had more prominent insomnia and cognitive slowing symptoms, as well as reduced frontal brain region activity and cognitive function on behavioral tests. This profile ultimately came to be called the “cognitive biotype.”
“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions. It’s mostly making observations and self-report measures,” explained Laura Hack, the study’s lead author.
“Imaging while performing cognitive tasks is rather novel in depression treatment studies.”
Following drug treatment, the researchers also found that the overall remission rate (or lack of depression symptoms) for the three antidepressants was 38.8% for patients with the cognitive biotype; meanwhile, a remission rate of 47.7% was observed among patients without it.
The drug that showed the most prominent difference rate was sertraline. About 35.9% of patients with the biotype experienced remission after taking this drug, compared to 50% of patients without the biotype.
Following this study, both Hack and Williams suggest that imaging and behavior measurement could pave the way for better mental health treatment by diagnosing depression biotypes.
“Depression presents in different ways in different people, but finding commonalities– like similar profiles of brain function– helps medical professionals effectively treat participants by individualizing care,” Williams noted.
Moving forward, patients could complete a simple survey either in doctors’ offices or even at home on their own computers. Then, if a patient displays a specific biotype, they could be referred for imaging to confirm the results before undergoing a new course of treatment.
To read the study’s complete findings, which have since been published in JAMA Network Open, visit the link here.
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