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Dealing with depression is not easy, and the most common treatments don’t work for everyone. Could biomarkers be the key to finding more treatment options?

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Go to CuriosityStream.com/Psych to learn more. { ♪INTRO }. Dealing with depression is not easy.

And it doesn’t help that it is really difficult to find effective treatments for it. Your genetics, your environment, and various factors in your brain all seem to play a role in whether you develop depression and how you experience it. So the most common treatments don’t work for everyone.

Some researchers think that the solution to this is personalized medicine: using information about a patient’s symptoms or even their genome to match them to drugs that actually help. “Personalized medicine” sometimes sounds like a futuristic buzzword, but there are already big projects looking into it — and they’re making some progress. So for depression, these kind of treatments might actually not be that far off. One of these projects is spearheaded by a group called CAN-BIND, short for Canadian Biomarker Integration Network in Depression.

This team has already published a handful of studies and is working on many more, and they’re mainly searching for biomarkers for depression. Biomarkers are defined pretty broadly by the larger scientific community, but they’re basically something a doctor or lab can reliably measure that tells them about your illness. Anything from your pulse to a specific hormone in your blood is fair game.

Doctors can use biomarkers to learn how well a patient is responding to a specific treatment, or they can use them to predict how likely a patient is to respond to treatments in general. But when it comes to depression, the most sought-after biomarkers by far are those that tie a specific drug to a patient’s response. Basically, markers that take out the guesswork and say, “If you take this, here’s what you can probably expect.” If we could find a marker like this for depression, doctors could do something like a blood test, look for a certain result, and then match someone to an effective antidepressant based on that.

Of course, we’re nowhere near that yet. But the CAN-BIND group is working on it, and even though there’s a long way to go, they’re learning a lot. For example, they’ve investigated whether or not people have gene expression markers that can predict how they’ll respond to medication.

These markers would be things like messenger RNAs that tell scientists how much protein is being made by a cell. Which could, in turn, affect how the body processes or responds to a drug. Scientists have studied a ton of potential markers, but unfortunately, the CAN-BIND team concluded in a 2017 review that none of them are ready for prime time just yet.

The results are too inconclusive — maybe because we don’t know enough about our genetic material. But that doesn’t mean we should give up on this method yet. It likely just means there’s more to learn.

In the meantime, though, the CAN-BIND team has also been looking at other kinds of biomarkers. In 2018, they published a review that looked at brain imaging rather than molecular markers. This time, they looked at how all kinds of treatments — including psychotherapy — could affect the brain, not just drugs.

And this time, they found some promising results. In this review, the team found studies that suggested that things like size and shape changes in several brain regions could be tied to specific treatments. For example, they cited previous research where both increased activity in the prefrontal cortex, and decreased activity in a handful of other regions, were associated with better symptom improvement in patients who underwent cognitive behavioral therapy.

In other words, there were specific brain features that predicted how well someone would respond to treatment. These results do need to be validated, but if they’re true, this essentially means a doctor could look at someone’s brain for things like increased prefrontal cortex activity. And if they found it, they could use that knowledge to recommend someone for therapy.

At the end of the day, CAN-BIND still has a lot to do, but they’re paving the way for some major advances in medicine. Looking for biomarkers isn’t the only way to approach personalized medicine, though. Another approach is to look for actual differences in the gene sequences among people.

We’re talking differences in those famous four DNA bases that make up someone’s genetic code. This approach has become more feasible in recent years as personal gene sequencing has become widely available, and as we’ve begun to understand how these gene variants function. For example, there’s a liver enzyme that processes certain medications, including some used to treat depression, before they ever reach the brain.

It’s called CYP2D6, I’m sure you’ll remember that and the gene that codes for it has over a hundred different variants, which might make chemical changes to medications that render them more or less effective. If we could track down all of these genetic changes, we could start to figure out how to tailor medications to someone’s personal genetic code. And another major research effort, called the GUIDED study, was a big step forward in that.

The study was published online in January 2019, and it split over a thousand patients with depression into two groups. In one group, doctors were allowed to use the results of a genetic test to look for potential drug interactions — ones that could make those drugs either more or less effective. In the other group, doctors couldn’t use that knowledge, and made their drug choices the old-fashioned way.

In the genetic testing group, both patients’ response to treatment and the number of people who experienced remission of their depression symptoms were significantly higher than in the business-as-usual group. And partway through the study, if patients were allowed to switch to a drug supported by their genetic tests, they also showed better rates of symptom improvement, treatment response, and remission. Which is potentially awesome news — especially since this was a large, carefully-controlled study.

Scientists will always call for more research, but the GUIDED trial shows that knowledge of a patient’s genes can potentially help them get better — especially if their depression has been otherwise tough to treat. So there is a lot of reason to be hopeful about the future of depression treatments, even if a lot more research is still needed. Whether it’s through biomarkers or our actual genes, we’re working on ways to know whether specific treatments will help specific people.

So maybe in the future, no one will ever need to go through three, four, or a dozen treatments to find something that works. We might figure out how to do it on the first try — and that’s worth celebrating. If you want to learn more about psychology — or other topics in fields like history or science — we think we’ve found some videos you might enjoy.

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There’s so much to learn! Like, Birth of the Internet is a show that can tell you about the internet you’re using to watch this episode right now! Did you know the first Internet message was transmitted way back in 1969, or that the foundations of the Web grew out of the Cold War?

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