Cognitive behavioral therapy enhances brain circuits to relieve depression

Cognitive behavioral therapy, one of the most common treatments for depression, can help people develop coping skills for everyday problems, reinforce healthy behaviors, and counter negative thoughts. But can changing thoughts and behaviors really produce lasting changes in the brain?

A new study led by the Stanford University School of Medicine finds that depression can be improved if the right treatment is matched to the right patient. 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 one-third of patients. These patients also showed adaptive changes in their brain circuitry.

Moreover, these neuroadaptations were evident after just two months of treatment and could predict which patients would benefit from longer-term treatment.

The findings add to the evidence that choosing treatment based on the neurological background of a patient’s depression, which varies from person to person, increases the chances of success.

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

“If you experience chest pain, your doctor will likely suggest tests such as an electrocardiogram, a heart scan and possibly blood tests to determine the cause and what treatment you should consider,” said Leanne Williams, PhD, the Vincent V. C. Wu Professor of Psychiatry and Behavioral Sciences at the Stanford University School of Medicine and director of the Center for Precision Mental Health and Wellness.

“But when it comes to depression, there’s no test. You feel the emotional pain broadly, but there’s no test to look at what’s going on in the brain, so choosing a treatment is trial and error.”

Williams and Jun Ma, MD, professor of medicine and geriatrics at the University of Illinois at Chicago, were co-authors of the paper. study Issued on September 4th Science Translational MedicineThe study is part of a larger clinical trial called RAINBOW (Research to Improve Both Mood and Weight).

Problem Solving

Problem-solving therapy, the type of cognitive behavioral therapy used in the trial, is designed to improve cognitive skills used in planning, problem-solving, and ignoring irrelevant information. Therapists help patients identify real-world problems (such as a conflict with a roommate), brainstorm solutions, and choose the best one.

These cognitive abilities depend on specific sets of neurons working together, called cognitive control circuits.

Previous work from the Williams lab has identified six biotypes of depression based on patterns of brain activity and estimated that a quarter of people with depression have dysfunctional cognitive control circuits (either too much or too little activity).

Participants in the new study were adults diagnosed with both severe depression and obesity, conditions that, when combined, often suggest problems with cognitive control circuits. Patients with this profile typically do poorly with antidepressants, with a response rate of just 17 percent.

Of the 108 participants, 59 received a year-long problem-solving therapy program in addition to their usual treatments, such as medication and visits to their GP. The remaining 49 received treatment as usual only.

Participants underwent fMRI brain scans at the start of the study, and then again at two, six, 12, and 24 months. During the brain scans, participants were tested by pressing or not pressing a button according to text on a screen, a task known to activate cognitive control circuits. This allowed the researchers to measure changes in activity in those circuits over the course of the study.

“We specifically wanted to see whether this problem-solving therapy could modulate cognitive control circuits,” said Xue Zhang, PhD, a postdoctoral researcher in psychiatry and lead author of the study.

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

Work Smarter

Like other depression treatments, problem-solving therapy doesn’t work for everyone, but 32% of participants responded to the therapy, reducing the severity of their symptoms by more than half.

“This is a big improvement over the 17 percent response rate to antidepressants,” Chan said.

When the researchers looked at brain scans, they found that the group that only received usual care experienced reduced activity in cognitive control circuits over the course of the study, which correlated with impaired problem-solving ability.

But in the treatment group, that pattern was reversed, with reduced activity correlating with improved problem-solving skills — the researchers suggest this may be because the brain learned to process information more efficiently through treatment.

“We think they have more efficient cognitive processing, which means they need fewer resources in their cognitive control circuits to perform the same behavior,” Chang says.

Before the treatment, their brains were working harder, but now they’re working smarter.

On average, both groups’ overall depression severity improved, but when Chan looked more closely at the 20-item depression assessment, he found that the depressive symptom most related to cognitive control — “everything feeling like an effort” — had benefited from the more efficient cognitive processing that came with treatment.

“We’re finding that we can identify specific areas of improvement in the cognitive aspects of depression, which have the greatest impact on real-world functioning and therefore are the most disabling,” Williams said.

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

A quick path to recovery

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

“This is important because it shows that brain changes are actually occurring early on, and within the expected time frame for brain plasticity,” Williams said. “Real-world problem solving literally changes the brain within a matter of months.”

The idea that thoughts and actions change brain circuits is not that different from how exercise (action) strengthens muscles, she added.

The researchers found that these early changes indicated which patients were responding to treatment, and were more likely to have improved problem-solving skills and depression symptoms 24 months, six months, 12 months, and even a year after treatment ended. This means that brain scans can be used to predict which patients will be best suited to problem-solving therapy.

It’s a step toward Williams’ vision of precision psychiatry, which uses brain activity to match patients with the treatments they’re most likely to benefit from, speeding up recovery.

“This is definitely a scientific advance,” Chang 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 study.