Cognitive behavioral therapy improves brain circuits to alleviate depression

Cognitive behavioral therapy, one of the most common treatments for depression, can teach skills to cope with everyday problems, reinforce healthy behaviors, and counter negative thoughts. But can changing thoughts and behaviors lead to lasting changes in the brain?

New research led by Stanford Medicine has found that it can, if a therapy is tailored to the right patients. In a study of adults with both depression and obesity, a hard-to-treat combination, cognitive behavioral therapy that focused on problem solving reduced depression in a third of patients. These patients also showed adaptive changes in their brain circuits.

Moreover, these neural adaptations were evident after just two months of therapy and could predict which patients would benefit from long-term therapy.

The findings add to the evidence that choosing treatments based on the neurological basis of a patient’s depression (which varies by person) increases the likelihood of success.

This same concept is already standard practice in other medical specialties.

“If you have chest pain, your doctor will suggest a number of tests — an electrocardiogram, a heart scan, perhaps a blood test — to determine the cause and what treatments should be considered,” says Leanne Williams, Ph.D., the Vincent V.C. Woo Professor, professor of psychiatry and behavioral sciences and director of the Center for Precision Mental Health and Wellness at Stanford Medicine.

“But with depression, there are no tests. You have this broad sense of emotional pain, but it’s a trial-and-error process to choose a treatment because we don’t have tests for what’s going on in the brain.”

Williams and Jun Ma, MD, Ph.D., professor of academic medicine and geriatrics at the University of Illinois at Chicago, are co-senior authors of the study published on September 4 in Science Translational MedicineThe work is part of a larger clinical trial called RAINBOW (Research Aimed at Improving Both Mood and Weight).

Troubleshooting

The form of cognitive behavioral therapy used in the trial, known as problem-solving therapy, is designed to improve cognitive skills used in planning, solving problems, and ignoring irrelevant information. A therapist guides patients through identifying real-world problems (such as a conflict with a roommate), brainstorming solutions, and choosing the best one.

These cognitive skills depend on a specific group of neurons working together, the so-called cognitive control circuit.

Previous research from Williams’ lab, which identified six biotypes of depression based on patterns of brain activity, found that a quarter of people with depression have dysfunction in their cognitive control circuits — either too much or too little activity.

The participants in the new study were adults with both major depression and obesity, a confluence of symptoms that often points to problems with cognitive control circuitry. Patients with this profile tend to do poorly on antidepressants: their response rate is a dismal 17 percent.

Of the 108 participants, 59 underwent a year-long program of problem-solving therapy in addition to their usual care, such as medications and visits to a general practitioner. The remaining 49 received only usual care.

They had fMRI brain scans at the start of the study, and then at two months, six months, 12 months, and 24 months. During the brain scans, the participants completed a test that required them to press or not press a button based on text on a screen, a task known to activate cognitive control circuitry. The test allowed researchers to measure changes in the activity of that circuit over the course of the study.

“We wanted to investigate whether this problem-solving therapy could modulate the cognitive control circuit in particular,” said Xue Zhang, Ph.D., a postdoctoral researcher in psychiatry and lead author of the study.

With each brain scan, participants also completed standard questionnaires assessing their problem-solving skills and depressive symptoms.

Working smarter

As with any other depression treatment, problem-solving therapy didn’t work for everyone. But 32% of participants responded to the therapy, meaning their symptom severity was reduced by half or more.

“That’s a huge improvement from the 17% response rate for antidepressants,” Zhang said.

When researchers examined the brain scans, they found that in the group that received only usual care, a cognitive control circuit that became less active over the course of the study correlated with worsening problem-solving skills.

But in the group that received therapy, the pattern was reversed: reduced activity correlated with improved problem-solving skills. The researchers believe this is because the therapy teaches their brains to process information more efficiently.

“We believe they have more efficient cognitive processing, meaning they now require fewer resources in the cognitive control circuit to perform the same behavior,” Zhang said.

Before the therapy, their brains worked harder; now they worked smarter.

Both groups improved, on average, in their overall severity of depression. But when Zhang dug deeper into the 20-item depression assessment, she found that the depression symptom most relevant to cognitive control — “feeling like everything is an effort” — benefited from the more efficient cognitive processing the therapy produced.

“We see that we can pinpoint the improvement specifically to the cognitive aspect of depression, which is the cause of disability because it has the greatest impact on real-world functioning,” Williams said.

Some participants reported that problem-solving therapy helped them think more clearly, which enabled them to return to work, resume hobbies, and manage their social interactions.

Fast track to recovery

Just two months into the study, brain scans showed changes in cognitive control circuit activity in the therapy group.

“That’s important because it tells us that there’s real change happening in the brain early on, and that’s in the time frame where you would expect brain plasticity to occur,” Williams said. “Real-world problem solving literally changes the brain in a matter of months.”

The idea that thoughts and behaviors can change brain circuits isn’t all that different from the way exercise — a behavior — strengthens muscles, she added.

The researchers found that these early changes indicated which patients were responding to therapy and were likely to show improvements in problem-solving skills and depressive symptoms at six months, 12 months, and even a year after the end of therapy, at 24 months. That means brain imaging could be used to predict which patients would be the best candidates for problem-solving therapy.

It’s a step toward Williams’ vision of precision psychiatry, which uses brain activity to match patients with the therapies likely to help them most, helping them recover faster.

“It’s definitely going to advance science,” Zhang said. “But it’s also going to change a lot of people’s lives.”

Researchers from the University of Washington, the University of Pittsburgh School of Medicine and Ohio State University also contributed to the work.