2 factors hugely impact whether antidepressants will work for you - and Stanford researchers have finally put them together

The sadness often descended like a curtain - heavy and dark.

But even when my depression threatened to cut me off completely from the world around me, I struggled with the decision to take antidepressants. It wasn't just that I'd been taught to believe that "going on meds" was giving up. No, what really worried me was how I'd cope if the drugs didn't work.

This is one of the biggest problems with our current methods of treating mental illness - it's virtually impossible to know if drugs will help.

"Right now, [going on antidepressants] is very much trial and error," Dr. Jeffrey Lieberman, the chair of the department of psychiatry at Columbia University, told Business Insider.

A group of Stanford researchers wants to change that. They've created a two-part test which they say could one day help predict - with striking accuracy - if someone with depression will respond to antidepressants. Their results were published in October in the journal Proceedings of the National Academy of Sciences.

At its essence, the test looks at two factors in someone with depression.

1. Specific patterns of brain function in one area of the brain that's thought to play a key role in depression.

The researchers looked specifically at brain activity in the amygdala, a small structure deep in the center of the brain. The amygdala is part of our limbic system, a group of structures linked with emotions like anger, sadness, pleasure, and fear. People with depression tend to display higher activity in the amygdala, which can continue even after recovery.

To get a snapshot of what was going on in people's amygdalas, the Stanford researchers showed their study participants images of emotional (angry and sad) faces while they sat in an MRI machine.

2. Exposure to stress in early life.

People who are exposed to high levels of stress in childhood, either from experiencing a single traumatic event or as the result of being repeatedly abused or neglected, tend to be at higher risk for depression than people who are not.

As a result, the Stanford researchers included this factor in their diagnostic test by having patients fill out an early life questionnaire designed to assess their exposure to things like abuse, family conflict, illness, and natural disasters before they were 18 years old.

What the test showed

Based on someone's "score" on the two measurements above - i.e. Did they show high patterns of brain activity when exposed to the emotional faces? Were they exposed to lots of early life stress? - the researchers were able to come up with a predictive snapshot of how well that person might respond to an antidepressant drug like Prozac or Zoloft.

The people who were the most likely to respond to antidepressants were those who'd experienced high levels of early life stress and were also highly reactive to specific emotional stimuli.

In other words, people with depression in the study who revealed that they'd been abused as a child and whose brain scans showed that they were highly reactive to the angry and sad faces were more likely to have a positive outcome on the drugs. Scientists believe that a stressful childhood experience like abuse can heighten our sensitivity to emotions, especially negative, potentially threatening ones. Eventually, this could make someone less sensitive to positive cues as well. The role of antidepressants in this scenario, then, would be to help normalize how our brain's amygdala reacts to emotional stimulii, especially positive cues.

The same outcome was predicted for people who'd experienced low levels of early life stress and were also not very reactive to the faces. In these people, the role of the drugs would be to heighten their brain's reactivity to emotional cues.

On the other hand, depressed people who said they'd experienced high levels of early life stress but did not react much to the faces (or people who experienced low levels of early life stress but were very reactive to the faces) tended to respond poorly to the drugs.

This jives with other research which suggests that exposure to early life stress, such as abuse or neglect, can change the structure and function of the amygdala, the structure linked with processing emotions. Scientists believe

'Racing towards the same goal'

The test results are promising, not just because the test appeared to work, but because the researchers' efforts are part of a bigger push towards transforming how we diagnose and treat mental illness.

For the vast majority of medical problems, there's a diagnostic test that can tell you what course of treatment you should embark on. If you think you may have type 1 diabetes, for example, you take a blood test. If it's positive, you'll likely be prescribed insulin. If you think you may have a heart problem, you get an EEG. Depending on the outcome, you might be given several different kinds of drugs or told to start a specific exercise regimen. With mental illness, there are virtually no such diagnostic tests.

The Stanford researchers aren't the only ones who see this as a huge problem. They're part of a growing number of scientists who are trying to create diagnostics for mental illness.

"This is one of many initiatives that are pointing towards how diagnostics will become a kind of standard of care," said Lieberman. "Everybody is racing towards the same goal but they're taking different paths."

"I believe [this] is one very important way to transform how we manage depression," Leanne M. Williams, a psychiatrist at Stanford University and one of the authors of the new paper, told Business Insider. "This could help close the gap between the insights we get from our research and the current devastating impact of depression."

Here's how it might work one day. Picture a scenario where someone with depression walks into a clinic, takes the test, and finds out she probably won't respond well to antidepressants. Then, she has options: First, she could either go on the drugs anyway and see what happens (the test does not predict the future - depression is complicated and there's still a chance that someone who performs one way on the test might have a different real life experience). Second, she might be encouraged to try a different route of treatment, such as talk therapy.

Like any new study, however, the present research has limitations.

For starters, the test has only been given to people with diagnosed depression in preliminary study settings so far. Researchers are still at the stage in their work where they're deciphering how well it works and for whom. In other words, you aren't going to see the test popping up at your doctor's office tomorrow. Still, the scientists who designed the test told Business Insider that they plan to start deploying it in limited real-world settings at Stanford University in the next few months.

"Anything that would help identify such individuals or give doctors an idea of how they'd respond to treatment would be beneficial," said Lieberman. "This is one piece of putting that bigger puzzle together. But it's not the final piece."