Cognitive behavioral therapy improves brain circuits to relieve depression

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

New research from Stanford Medicine has shown that it is possible, as long as you choose the right therapy for your patients. In a study of adults with both depression and obesity (a difficult combination to treat), cognitive behavioral therapy focused on problem-solving reduced depression in a third of the patients. These patients also showed adaptive changes in their brain circuits.

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

These findings add to evidence that choosing treatments based on the neurological underpinnings of a patient’s depression – which vary from person to person – increases the chances of success.

The same concept is already common practice in other medical specialties.

“If you have chest pain, your doctor will suggest a few tests — an EKG, a heart scan, maybe a blood test — to figure out the cause and what treatments to consider,” said Leanne Williams, Ph.D., the Vincent V. C. Woo Professor of Psychiatry and Behavioral Sciences and director of the Center for Precision Mental Health and Well-Being at Stanford Medicine.

“Yet in depression, we don’t use any tests. You have a broad idea of ​​emotional pain, but choosing a treatment is a trial and error process because we don’t have any tests to determine what’s going on in the brain.”

Williams and Jun Ma, MD, PhD, professor of academic medicine and geriatrics at the University of Illinois at Chicago, are co-senior authors of the study published Sept. 4 in Scientific translational medicineThis work is part of a larger clinical trial called RAINBOW (Research to Improve Mood and Weight).

Problem solving

The cognitive behavioral therapy used in the trial, called problem-solving therapy, is designed to improve the cognitive skills used to plan, solve problems, and ignore irrelevant information. A therapist helps patients identify real-world problems (a conflict with a roommate, for example), brainstorm solutions, and choose the best one.

These cognitive skills depend on a particular set of neurons working together, known as the cognitive control circuit.

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

Participants in the new study were adults diagnosed with both major depression and obesity, a combination of symptoms that often indicates problems with the cognitive control circuit. Patients with this profile typically respond poorly to antidepressants: their response rate is a dismal 17 percent.

Of the 108 participants, 59 received a yearlong program of problem-solving therapy in addition to their usual care, such as medications and visits to a primary care doctor. The other 49 received only usual care.

Participants underwent fMRI brain scans at the beginning of the study, and after two months, six months, 12 months, and 24 months. During these scans, they completed a test of whether or not to press a button based on text displayed on a screen, a task known to engage the cognitive control circuit. The test allowed the researchers to assess changes in activity in this circuit throughout the study.

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

At each brain scan, participants also completed standard questionnaires that assessed their problem-solving abilities and symptoms of depression.

Work smarter

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

“This is a huge improvement over the 17% response rate for antidepressants,” Zhang said.

When the researchers looked at the brain scans, they found that in the group receiving only usual care, a cognitive control circuit that became less active over the course of the study was correlated with worse problem-solving ability.

But in the group that got therapy, the trend was reversed: reduced activity correlated with better problem-solving skills. The researchers think this may be because their brains learned to process information more efficiently through therapy.

“We think they have more efficient cognitive processing, which means they now need fewer resources in the cognitive control circuit to perform the same behavior,” Zhang said.

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

On average, both groups saw improvements in their 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 effective cognitive processing achieved through therapy.

“We find that we can identify improvement specific to the cognitive aspect of depression, which is the root of the disability because it has the greatest impact on real-world functioning,” Williams said.

Indeed, some participants reported that problem-solving therapy helped them think more clearly, enabling them to return to work, resume hobbies, and manage social interactions.

Fast track to recovery

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

“This is important because it tells us that real brain change is happening very early, and this is in the period when we would expect brain plasticity,” 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 is not so different from how 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 improve their problem-solving skills and depressive symptoms six months, 12 months, and even a year after therapy ended, or 24 months. This means that a brain scan could be used to predict which patients are the best candidates for problem-solving therapy.

It’s a step toward Williams’ vision of precision psychiatry: using brain activity to match patients with the therapies most likely to help them, guiding them more quickly toward recovery.

“It certainly advances science,” Zhang said. “But it’s also going to transform 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.