New Research May Predict if a Depression Treatment Will Work or Not

Researchers are bringing together imaging and AI to understand the variations, causes, and potential treatments of depression.


The question might come out of the blue at your checkup and take you a moment to understand: “How are you feeling?" Ah, what your doctor is asking is if you're depressed. Or maybe you know you're depressed, and have made an appointment to get some help. Either way, the demoralizing — or should we say “depressing?" — truth is the doctor only has a couple of things to suggest, and no clue as to which, if either, will work:

  • Talking to someone, which is to say receive cognitive behavioral therapy (CBT).
  • Taking medications, most typically an SSRI or an SNRI drug.
  • They're equally effective, but mostly not — only about 40% of patients will see improvement, according to Vox. Stanford professor Leanne Maree Williams tells Vox, “It is currently complete primitive guesswork. It's hard to imagine how you can do worse than the current situation, to be honest." And that's a problem. The NIH estimates that 16.1 million American adults experienced at least one depressive episode in 2015.

    The Mayo Clinic defines “depression" this way: “Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest." Beyond that, it's most likely a number of conditions lumped into one, and hence there's no universally effective treatment.

    Here's what we mean. A formal diagnosis of depression requires a patient to have five of the following criteria from the Diagnostic and Statistical Manual of Mental Disorders:

    1. Depressed mood or irritable most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
    2. Decreased interest or pleasure in most activities, most of each day
    3. Significant weight change (5%) or change in appetite
    4. Change in sleep: Insomnia or hypersomnia
    5. Change in activity: Psychomotor agitation or retardation
    6. Fatigue or loss of energy
    7. Guilt/worthlessness: Feelings of worthlessness or excessive or inappropriate guilt
    8. Concentration:diminished ability to think or concentrate, or more indecisiveness
    9. Suicidality:Thoughts of death or suicide, or has suicide plan

    Not only are all these symptoms unlikely to share a common cause, but even the same symptom can spring from different biological triggers. “It may be the case that, yes, perhaps there are hundreds of kinds of depression," says research psychiatrist Conor Liston at Weill Cornell Medical College. “There's a feeling of frustration that I share with most psychiatrists that a lot of our work is trial and error. And so it's frustrating to not have more objective data to drive our decision-making."

    Liston is now engaged in a project to identify the various subtypes of depression using fMRI scans and machine learning. He and a team of American and Canadian scientists scanned 1,118 subjects in a resting state, a huge sample for a study such as this. As subjects lay there, doing nothing in particular, the fMRI scanners kept an eye on their brains, looking to find two or more regions that tended to be active at the same time. The stronger the correlation, the stronger these areas' connections were assumed to be. By studying resting-state activity, the idea was to discern each patient's “default" connections. Of the 1,118 subjects, 458 were diagnosed depressives.

    The team tasked their AI with seeing if it could identify patients with depression based on their connections and, amazingly, the computer got it right 84% of the time.

    Next, the computer looked at only the scans from depressed subjects to see if it could detect brain activity that signified depression. It came up with four depression-related subtypes of activity, or “biotypes," that described the interaction between the medial prefrontal cortex and other areas. The medial prefrontal cortex is believed to be involved in thought about oneself.

    The four biotypes are:

  • Biotype 1 is associated with anxiety, insomnia, and fatigue.
  • Biotype 2 is associated with exhaustion and low energy.
  • Biotype 3 is associated with an inability to feel pleasure as well as slowed movements and speech.
  • Biotype 4 is associated mostly with anxiety with insomnia along with the inability to feel pleasure.
  • Liston was also interested in seeing how the chances of successful treatment differed between biotypes, and performed transcranial magnetic stimulation (TMS) on his depressed subjects. It's a non-invasive treatment that doctors may resort to when talk-based and medicinal therapies don't work.

    He found that TMS was more than three times more likely to succeed in Biotype 1 patients than in Biotype 2 and 4.

    Another research team using fMRIs and machine learning approached the problem from essentially the opposite direction, and wound up with very similar results, though their biotypes were a bit different than Liston's. After taking resting-state fMRI scans of 122 depression sufferers, they treated the subjects for 12 weeks using either CBT or medications (SSRIs or SNRIs). At the end of that time, the subjects were asked if their depression had been resolved, and the researchers then had their computer look through the fMRIs to see if it could detect brain activity patterns that corresponded to the success stories.

    Psychologist W. Edward Craighead, one of this team's scientists, tells Vox that, “The type of brain that responds to psychotherapy is where there's a strong pattern of connectivity between the frontal areas of the brain, which are involved more in thinking, talking, and problem solving, etc., with other portions of the brain. Whereas people who have low connectivity — the opposite pattern — respond to the medication."

    Statistically, subjects who got better and had strong connections had a 76% likelihood of responding well to CBT, and just a 5-10% of responding to medication. For those with weaker connections, the findings were flipped: They had a 50% chance of succeeding on meds and just 5% odds of getting better via CBT. Given that only 58 participants clearly got better, the study has a small sample size — only 58 participants clearly got better — and so further studies would be needed to verify its findings.

    In any event, both of these studies represent a beginning for combining AI and fMRIs to nail down the mechanics of depression, and work out the optimal treatments for this often intractable and life-diminishing condition.

    Yug, age 7, and Alia, age 10, both entered Let Grow's "Independence Challenge" essay contest.

    Photos: Courtesy of Let Grow
    Sponsored by Charles Koch Foundation
    • The coronavirus pandemic may have a silver lining: It shows how insanely resourceful kids really are.
    • Let Grow, a non-profit promoting independence as a critical part of childhood, ran an "Independence Challenge" essay contest for kids. Here are a few of the amazing essays that came in.
    • Download Let Grow's free Independence Kit with ideas for kids.
    Keep reading Show less

    Four philosophers who realized they were completely wrong about things

    Philosophers like to present their works as if everything before it was wrong. Sometimes, they even say they have ended the need for more philosophy. So, what happens when somebody realizes they were mistaken?

    Sartre and Wittgenstein realize they were mistaken. (Getty Images)
    Culture & Religion

    Sometimes philosophers are wrong and admitting that you could be wrong is a big part of being a real philosopher. While most philosophers make minor adjustments to their arguments to correct for mistakes, others make large shifts in their thinking. Here, we have four philosophers who went back on what they said earlier in often radical ways. 

    Keep reading Show less

    Withdrawal symptoms from antidepressants can last over a year, new study finds

    We must rethink the "chemical imbalance" theory of mental health.

    Bottles of antidepressant pills named (L-R) Wellbutrin, Paxil, Fluoxetine and Lexapro are shown March 23, 2004 photographed in Miami, Florida.

    Photo Illustration by Joe Raedle/Getty Images
    Surprising Science
    • A new review found that withdrawal symptoms from antidepressants and antipsychotics can last for over a year.
    • Side effects from SSRIs, SNRIs, and antipsychotics last longer than benzodiazepines like Valium or Prozac.
    • The global antidepressant market is expected to reach $28.6 billion this year.
    Keep reading Show less

    Is there a limit to optimism when it comes to climate change?

    Or is doubt a self-fulfilling prophecy?

    David McNew/Getty Images
    Politics & Current Affairs

    'We're doomed': a common refrain in casual conversation about climate change.

    Keep reading Show less
    Scroll down to load more…