Cognitive behavioral therapy, one of the most common treatments for depression, can teach coping skills, reinforce healthy behaviors, and address negative thoughts. But can changing thoughts and behaviors lead to permanent changes in the brain?
New research led by Stanford Medicine found that it can -? if a treatment is matched to the right patients. In a study of adults with depression and obesity -? a difficult 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 circuitry.
Furthermore, these neural adaptations were evident after just two months of treatment and could predict which patients would benefit from long-term treatment.
The findings reinforce evidence that choosing treatments based on the neurological background of a patient’s depression – which differ between people -; increases the chances of success.
The same concept is already established practice in other medical specialties.
“If you’ve had chest pain, your doctor would suggest some tests—an electrocardiogram, a heart scan, maybe a blood test—to determine the cause and what treatments to consider,” said Leanne Williams, PhD, Vincent VC Woo. Professor, professor of psychiatry and behavioral sciences, and director of Stanford Medicine’s Center for Precision Mental Health and Wellness.
“But in depression, we don’t use tests. You have this broad sense of emotional pain, but it’s a process of trial and error to choose a treatment because we don’t have tests for 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 Science Translational Medicine. The work is part of a larger clinical trial called RAINBOW (Research to Improve Mood and Weight).
Solving problems
The form of cognitive behavioral therapy used in the trial, known as problem-solving therapy, is designed to improve the cognitive skills used in planning, problem solving, and coordinating irrelevant information. A therapist guides patients in identifying real-life problems – a conflict with a roommate, say -; brainstorming and choosing the best one.
These cognitive skills 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 cognitive control circuits. either too much or too little activity.
The participants in the new study were adults diagnosed with major depression and obesity, a confluence of symptoms that often indicate problems with cognitive control circuitry. Patients with this profile generally do not do well on antidepressants: They have a dismal 17% response rate.
Of the 108 participants, 59 underwent an annual problem-solving treatment 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 were given fMRI brain scans at the start of the study, then after two months, six months, 12 months and 24 months. During the brain scans, participants completed a test that involved pressing or not pressing a button according to text on a screen -? a task known to engage cognitive control circuitry. The test allowed the researchers to measure changes in the activity of this circuit throughout the study.
“We wanted to see if this problem-solving therapy in particular could modify the cognitive control circuit,” said Xue Zhang, PhD, a postdoctoral fellow in psychiatry who is the study’s lead author.
With each brain scan, participants also completed standard questionnaires assessing problem-solving ability and depressive symptoms.
Working smarter
As with any treatment for depression, problem-solving therapy did not work for everyone. But 32% of participants responded to the treatment, meaning the severity of their symptoms was cut in 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 that received only usual care, a cognitive control circuit that became less active during the study was associated with worse problem-solving ability.
But in the treatment group, the pattern was reversed: reduced activity was associated with enhanced problem-solving ability. The researchers believe this may be because their brains are learning, 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 circuit to do the same behavior,” Zhang said.
Before the treatment, their brains worked harder. now, they worked smarter.
Both groups, on average, improved their overall depression severity. But when Zhang dug deeper into the 20-item depression assessment, she found that the symptom of depression was more related to cognitive control -? “Feeling everything is an effort” -? benefited from more efficient cognitive processing gained from treatment.
“We see that we can detect improvement in the cognitive aspect of depression, which is what drives disability because it has the biggest impact on real-world functioning,” Williams said.
Indeed, some participants reported that problem-solving therapy helped them think more clearly, allowing them to return to work, resume hobbies, and manage social interactions.
Speedy road to recovery
Just two months into the study, brain scans showed changes in cognitive control circuit activity in the treatment group.
“This is important, because it tells us that there is a real brain change that happens early, and it’s in the time frame that you 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 modify brain circuits is not so different from how exercise -? a behavior -? it strengthens the muscles, he added.
The researchers found that these early changes signaled which patients were responding to treatment and were likely to improve problem-solving skills and depression symptoms at six months, 12 months and even a year after treatment ended, 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 is a step towards Williams’ vision of precision psychiatry -? using brain activity to match patients with the treatments most likely to help them, fast-tracking them to recovery.
“It definitely advances science,” Zhang said. “But it will also 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.
The study received funding from the National Institutes of Health (grants UH2 HL132368, UH3 HL132368, and R01 HL119453).
