Cognitive behavioral therapy, one of the most common treatments for depression, can teach coping skills, reinforce healthy behaviors, and counteract negative thoughts. But can altering thoughts and behaviors lead to lasting changes in the brain?
Cognitive Behavioral Therapy for Depression
A new research conducted by Stanford Medicine found that it can, if a therapy is matched to the right patients. In a study of adults with depression and obesity, a difficult-to-treat combination, problem-solving-focused cognitive behavioral therapy reduced depression in a third of patients. These patients also showed adaptive changes in their brain circuits.
Furthermore, these neural adaptations were evident after only two months of therapy and could predict which patients would benefit from long-term therapy.
These findings reinforce evidence that choosing treatments based on the neurological basis of a patient’s depression, which varies from person to person, increases the likelihood of success. The same concept is already standard practice in other medical specialties.
“If you have chest pain, your doctor will recommend some tests, such as an EKG, a heart scan, maybe a blood test, to find 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 Wellness at Stanford Medicine.
“And yet in depression we don’t have any tests in use. 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 any tests for what’s happening in the brain.”
Williams and Jun Ma, M.D., Ph.D., professor of academic medicine and geriatrics at the University of Illinois at Chicago, are co-senior authors of the study published in Science Translational Medicine . The work is part of a larger clinical trial called RAINBOW (Research Aimed at Improving Both Mood and Weight).
The form of cognitive behavioral therapy used in the trial, known as problem-solving therapy, is designed to improve cognitive skills used in planning, problem solving, and filtering out irrelevant information. A therapist guides patients in identifying real-life problems, such as a conflict with a roommate, brainstorming solutions, and choosing the best one.
These cognitive abilities depend on a specific set of neurons working together, known as a 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 confluence of symptoms that often indicates problems with cognitive control circuitry. Patients with this profile typically do poorly on antidepressants: They have a disastrous 17 percent response rate.
Of the 108 participants, 59 received a year-long program of problem-solving therapy in addition to usual care, such as medications and visits to the primary care physician. The other 49 received only usual care.
They underwent 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, participants completed a test that involved whether or not to press a button based on text on a screen, a task known to engage the cognitive control circuitry. The test allowed researchers to assess changes in activity in that circuit during the study.
“We wanted to test whether this particular problem-solving therapy could modulate the cognitive control circuitry,” 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 assessing their problem-solving ability and symptoms of depression.
As with any treatment for depression, problem-solving therapy didn’t work for everyone. But 32 percent of participants responded to therapy, meaning their symptoms decreased in severity by half or more.
“This is a huge improvement over the 17 percent response rate seen for antidepressants,” Zhang said.
When the researchers examined 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 worsening problem-solving skills.
But in the therapy group, the pattern reversed: less activity correlated with better problem-solving skills. Researchers think this may be because their brains learned, through therapy, to process information more efficiently.
“We think they have more efficient cognitive processing, which means they now need fewer resources in the cognitive control circuitry to perform the same behavior,” Zhang said.
Before the therapy, their brains worked harder; now, however, they worked smarter.
Both groups, on average, improved overall depression severity. But when Zhang dug deeper into the 20-item depression assessment, he found that the depression symptom most relevant to cognitive control, “feeling like everything is an effort,” benefited from the improved cognitive processing that therapy brought.
“We’re seeing that we can specifically target the cognitive aspect of depression, which is what drives disability because it has the greatest impact on real-life functioning,” Williams said.
In fact, some participants reported that problem-solving therapy helped them think more clearly, enabling them to return to work, resume their hobbies, and manage social interactions.
Just two months into the study, brain scans showed changes in the activity of the cognitive control circuitry in the therapy group.
“It’s important because it tells us that there’s real brain change happening early on, and it’s in the time frame where you would expect brain plasticity,” Williams said. “Real-world problem solving is literally changing the brain in a couple of months.”
The idea that thoughts and behaviors can change brain circuits is not all that different from the way exercise, or behavior, strengthens muscles, he added.
The researchers found that these early changes signaled which patients were responding to therapy and were likely to improve problem-solving skills and symptoms of depression at six months, 12 months, and even a year after the end of therapy, at 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, which uses brain activity to match patients with the therapies best suited to help them, speeding their recovery.
“It’s definitely advancing 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 The Ohio State University also contributed to the study.
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