Cognitive behavioral therapy, one of the most common treatments for depression, can teach coping skills, reinforce healthy behaviors, and counteract negative thoughts. But can changing thoughts and behaviors produce lasting changes in the brain?
New research led by Stanford Medicine has found that it can — if the therapy is tailored to the right patients. In a study of adults with depression and obesity (a difficult-to-treat combination), cognitive behavioral therapy focused on problem solving reduced depression in one-third of patients. These patients also showed adaptive changes in their brain circuits.
What’s more, 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 evidence that choosing treatments based on the neurological underpinnings of a patient’s depression (which vary among people) increases the odds of success.
The same concept is already standard practice in other medical specialties.
“If you were having chest pain, your doctor would suggest some tests — an EKG, a CT scan of your heart, maybe a blood test — to determine the cause and what treatments to consider,” said Leanne Williams, PhD, the Vincent VC Woo Professor, professor of psychiatry and behavioral sciences and director of the Precision Mental Health and Wellness Center at Stanford Medicine.
“But in the case of depression, there are no tests. There is a broad sense of emotional pain, but it is a trial and error process to choose a treatment, because we don’t have tests to know what is happening 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 September 4 in Scientific Translational Medicine. The work is part of a larger clinical trial called RAINBOW (Research Targeting 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, problem-solving and eliminating irrelevant information. A therapist guides patients to identify real-life problems (a conflict with a roommate, for example), brainstorm solutions and choose the best one.
These cognitive abilities 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 one-quarter of people with depression have dysfunction in their cognitive control circuits (too much or too little activity).
The participants in the new study were adults who had been diagnosed with major depression and obesity, a combination of symptoms that often indicates problems in the cognitive control circuit. Patients with this profile generally do not respond well to antidepressants: they have a dismal response rate of 17%.
Of the 108 participants, 59 underwent a year-long problem-solving therapy program in addition to their usual care, such as medications and visits to a 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, six, twelve, and twenty-four months. During the brain scans, participants completed a test that involves pressing or not pressing a button based on text on a screen — a task known to activate the cognitive control circuit. The test allowed researchers to measure changes in that circuit’s activity over the course of the study.
“We wanted to see if this particular problem-solving therapy could modulate the cognitive control circuit,” said Xue Zhang, PhD, a postdoctoral researcher in psychiatry and senior author of the study.
With each brain scan, participants also completed standard questionnaires assessing their problem-solving ability and depression symptoms.
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 was reduced by half or more.
“This is a huge improvement over the 17% response rate seen with antidepressants,” Zhang said.
When the 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 ability.
But in the group that received therapy, the pattern was reversed: decreased activity correlated with increased problem-solving ability. Researchers believe this may be because their brains learned, through therapy, to process information more efficiently.
“We think they have more efficient cognitive processing, meaning 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 improved overall depression severity. 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 gained from the therapy.
“We’re seeing that we can identify specific improvement in the cognitive aspect of depression, which is what drives disability because it has the greatest impact on real-world functioning,” Williams said.
In fact, some participants reported that problem-solving therapy helped them think more clearly, allowing them to return to work, resume their hobbies, and manage 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 brain change is happening at an early stage, and it’s happening in the time frame in which you’d expect brain plasticity to occur,” Williams said. “Real-world problem solving is literally changing the brain in a couple of months.”
The idea that thoughts and behaviors can modify brain circuits is not so different from how exercise (a behavior) strengthens muscles, he added.
The researchers found that these early changes indicated which patients were responding to the therapy and were likely to improve their problem-solving skills and depression symptoms six, twelve, and even a year after finishing therapy – that is, 24 months. This means that brain scans 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, speeding recovery.
“This is certainly a scientific breakthrough,” Zhang said. “But it will also transform the lives of many people.”
Researchers from Washington University, the University of Pittsburgh School of Medicine and Ohio State University also contributed to the work.
The study received funding from the National Institutes of Health (grants UH2 HL132368, UH3 HL132368, and R01 HL119453).