As science searches for answers to depression


Currently, more than one in 10 Americans is on medication for depression – a number that has risen during the pandemic.

But how do these drugs work—and why don’t they work for everyone? And why do people get depression in the first place?

Experts do not yet know all the answers to these questions. After all, the brain is a complicated place. But they do know that depression has its roots in everything from the genes we are born with to the experiences we had in our early years to what is happening in our lives right now.

At the same time, they know that many people with depression can get help from antidepressants—and from talk 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 gets a lot of attention.

He worries that over-simplified news and social media posts may lead some people to question whether they should continue to take anti-depression drugs that target the brain’s serotonin system.

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

Important insights for people with depression

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

“Do we need to understand exactly how a drug or non-drug treatment works in order to use it? No — if that were true, we wouldn’t have any treatment options for depression, whether it be 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 changes when we are in a phase of depression is incredibly complex and our current understanding is limited.”

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

But, says Sen, “For people currently dealing with depression, the information we get from clinical trials should guide care. And clinical studies show that SSRIs are moderately effective and, along with other medications and psychotherapy, play an important role in the treatment of depression.”

In other words, “If a treatment or combination of treatments prescribed or recommended by your healthcare provider is working for you, great – stick with it.” Your personal experience with the treatment is far more relevant than this study. And if you’re using antidepressant medication or other therapy and aren’t getting relief from your depression symptoms, talk to your doctor.”

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 brain chemicals called neurotransmitters that helps brain cells “talk” to each other by attaching to receptors on the cells’ outer surfaces.

The new study, which is getting a lot of attention, looks at many older studies on serotonin and tries to draw conclusions by combining the information from them.

The study did not perform any new experiments or even combine previous studies into a meta-analysis. Instead, the researchers conducted an “umbrella review” of some, but not all, meta-analyses related to serotonin.

Randomly, Another such “study of studies” on serotonin and depression was published just a week before the one that was in the news. It concluded that variations in the serotonin transporter gene play a key role in depression risk, combined with stressful experiences throughout a person’s life. But this study hasn’t gotten nearly as much attention.

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

looking ahead

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

“In the brain, we now have much better tools to more directly study how neurotransmitters work and neural circuitry changes than we did 20 to 30 years ago, when many of the primary studies covered in the Umbrella review were conducted,” he notes Celebration . “Furthermore, we can now computationally combine information across many study levels and many patients in a way that wasn’t possible before.”

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

By examining people living with high levels of stress and varied schedules — like the thousands of new doctors in the Internal health study that Sen is leading – they learn more about how these factors interact.

At the same time, researchers at UM and beyond are studying ketamine, esketamine, ECT, talk therapy, and even psychedelics like psilocybin, which is derived from mushrooms, to see what effects they have and who responds best to them. They are Seeking people with depression, anxiety, and other medical conditions to participate in carefully controlled research studies.

“Fundamental research is critical to identifying new targets and understanding what happens in the brain when we become depressed or anxious, and may eventually lead to the development of new treatments that work better and reach more patients,” says Sen. “But we don’t need to know the exact molecular mechanisms to act on clinical trial data showing the beneficial effects of interventions like better sleep, cognitive behavioral therapy, or SSRIs.”

The future of depression treatment could be much more personalized to the individual patient, just as cancer treatment has become.

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


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