As science searches for answers on depression

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Right now, more than one in 10 Americans take medication for depression — a number that has increased during the pandemic.

But how do these drugs work – and why don’t they work for everyone? And why do people get depressed anyway?

Experts still don’t know all the answers to these questions. After all, the brain is a complicated place. But they know depression has its roots in everything from the genes we’re born with, to the experiences we had in our early years, to what’s going on in our lives right now.

At the same time, they know that many people with depression get help from antidepressants – and talk-based therapy, better sleep, exercise, more social interaction and, in severe cases, treatments like ketamine and ECT.

The bottom line is that people with symptoms of depression seek help and keep trying until they find something that works for them.

That’s why the director of the nation’s first depression center, Srijan Sen, MD, Ph.D., is concerned about the impact of a new study on the role of serotonin in depression that’s getting a lot of buzz. Warning.

He worries that oversimplified reporting and social media posts may cause some people to wonder if they should continue taking depression drugs that target the brain’s serotonergic system.

These drugs, called SSRIs, are far from perfect, he says. But there is ample evidence that they work for many people.

Top takeaways for people with depression

Sen directs the Eisenberg Family Depression Center, which has brought together University of Michigan researchers for more than 20 years. His own research has explored the roots of depression for over two decades. He is both a depression scientist and a psychiatrist who has treated many people with depression.

“Do you need to understand precisely how a drug or non-drug treatment works in order to use it? No, if that were true, we wouldn’t have any treatment for depression, whether it’s medications like SSRIs, psychotherapies like cognitive therapy, or lifestyle changes like more consistent sleep patterns. he says. “The biology of the brain, and how the brain looks different when we are in an episode of depression, is incredibly complex and our current understanding is limited.”

There is no doubt that basic science, including research on serotonin and genetic variation among people with depression, is crucial to our search for future better treatments and more personalized treatment. EFDC members – who come from many areas of UM – are helping to conduct this research.

But, says Sen, “For people struggling with depression right now, the information we get from clinical trials should guide care. And clinical trials indicate that SSRIs are moderately effective and play an important role in treating depression, along with other medications and psychotherapy.

In other words, “If a treatment or combination of treatments prescribed or recommended by your health care provider works for you, that’s great – keep going. Your personal experience with the treatment is far more relevant than this study. And if you’re using depression medication or another therapy and you’re not getting relief from your depression symptoms, talk to your healthcare provider.

The State of Serotonin Science

Sen notes that mental health experts certainly don’t believe that a simple “chemical imbalance” is the root cause of depression.

Serotonin is one of the main chemicals in the brain, called neurotransmitters, which helps brain cells “talk” to each other by connecting to receptors on the outer surfaces of cells.

The new study that is getting a lot of attention looks at many older studies on serotonin and tries to draw conclusions by combining the information they contain.

The study did not conduct new experiments or even combine previous studies in a meta-analysis. But instead, the researchers conducted a “global review” of some, but not all, meta-analyses related to serotonin.

Coincidentally, another “study of studies” on serotonin and depression was released just a week before the one that’s making the news. He concluded that variations in the serotonin transporter gene play a key role in the risk of depression, in combination with stressful experiences throughout a person’s life. But this study has not received as much attention.

In other words, says Sen, the science of serotonin’s exact role is far from settled.

Look forward

Sen and his colleagues hope that new studies, using modern tools that allow scientists to look at far more information from far more patients than those older studies, will accelerate progress in treating depression.

“In the brain, we now have much better tools to look more directly at how neurotransmitters act and neural circuits change than 20 to 30 years ago, when many of the primary studies covered by the umbrella review were conducted.” , he notes. . “Additionally, we can now combine information from many study levels and many patients in a way that was not possible before.”

Sen and his colleagues, for example, are working to determine how different combinations of genetic differences, combined with life events and current lifestyle, including sleep patterns, affect depression risk or response to depression. treatment.

By studying people who live with intense stress and flextime — like the thousands of new doctors in the Sen-led Internal Health Study — they’re learning more about how these factors interact.

At the same time, researchers at UM and elsewhere are studying ketamine, esketamine, ECT, talk therapy, and even psychedelic drugs like the mushroom-derived psilocybin to see what effect they have. have and who responds the most. They are looking for people with depression, anxiety, and other conditions to participate in carefully controlled research studies.

“Basic science is critically important to identifying new targets and understanding what is happening in the brain when we are depressed or anxious, and may eventually lead to the development of new treatments that will work better and for more patients,” says Sen. “But we don’t need to know the precise molecular mechanisms to act on clinical trial data that show the positive effects of interventions like better sleep, cognitive behavioral therapy, or SSRIs.

The future of depression treatment could be much more personalized for each patient, just as cancer treatment has become.

“We need new drugs that work better, and we need to figure out how to get the right treatment to the right patient at the right time,” Sen says. “We all have different vulnerabilities and sensitivities.”

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