Scientists have discovered that specific changes in brain activity can indicate which patients will gain from cognitive behavioral therapy.
Cognitive behavioral therapy (CBT) is a popular treatment for depression, helping individuals develop skills to handle daily challenges, encourage healthy habits, and challenge negative thinking. But does modifying thoughts and behaviors actually result in permanent brain changes?
New research spearheaded by Stanford Medicine shows that it can—especially when therapy is tailored to the right individuals. In a study involving adults struggling with both depression and obesity—a pair of conditions that are tough to treat—problem-solving cognitive behavioral therapy reduced depression in a third of participants. These patients also displayed advantageous alterations in their brain circuitry.
Interestingly, these brain changes were observable after just two months of therapy and served as indicators of which patients would benefit from sustained treatment.
This research underscores that selecting treatment based on the neurological aspects of a patient’s depression—which can differ significantly from person to person—enhances the likelihood of effective outcomes.
This tailored approach is already a standard practice in other areas of healthcare.
“If you’re experiencing chest pain, your doctor would recommend various tests—like an electrocardiogram, a heart scan, or perhaps a blood test—to determine the cause and potential treatments,” explained Leanne Williams, PhD, the Vincent V.C. Woo Professor, a psychiatry and behavioral sciences professor, and the head of Stanford Medicine’s Center for Precision Mental Health and Wellness.
“However, in the realm of depression, we lack such diagnostic tests. The experience of emotional pain can be vague, leading to a trial-and-error method in treatment selection, since no assessments exist to clarify brain activity.”
Williams and Jun Ma, MD, PhD, a professor at the University of Illinois at Chicago, are co-senior authors of the study, which was published on September 4 in Science Translational Medicine. This research is part of a larger clinical initiative known as RAINBOW (Research Aimed at Improving Both Mood and Weight).
Problem Solving
The form of cognitive behavioral therapy utilized in the trial, termed problem-solving therapy, aims to enhance cognitive skills in areas like planning, troubleshooting, and filtering out extraneous information. A therapist assists patients in pinpointing real-life issues—like conflicts with roommates—brainstorming feasible solutions, and selecting the best option.
These cognitive abilities rely on a specific group of neurons that work in concert, known as the cognitive control circuit.
Prior studies from Williams’ lab identified six biotypes of depression based on differing brain activity patterns. It was estimated that about 25% of individuals with depression exhibit dysfunction in their cognitive control circuits, with either excessive or insufficient activity.
The participants in the recent study were adults diagnosed with both major depression and obesity, a combination typically linked to cognitive control circuit issues. Individuals with this profile often exhibit poor outcomes with antidepressant medications, showing a grim response rate of just 17%.
Of the 108 participants, 59 received a year-long program of problem-solving therapy in conjunction with their standard care, such as medications and visits to healthcare providers. The remaining 49 participants only received standard care.
These participants underwent fMRI brain scans at various intervals: initially, then after two, six, twelve, and twenty-four months. During these scans, they performed a task involving pressing or refraining from pressing a button based on on-screen text—a test known to stimulate the cognitive control circuit. This allowed the researchers to monitor changes in activity within this circuit throughout the study.
“We aimed to determine whether this specific problem-solving therapy could have an impact on the cognitive control circuit,” said Xue Zhang, PhD, a postdoctoral researcher in psychiatry and the study’s lead author.
Every time they underwent a brain scan, participants also completed standard assessments measuring their problem-solving abilities and depression symptoms.
Working Smarter
As with any treatment for depression, problem-solving therapy wasn’t effective for everyone. However, 32% of participants experienced significant improvement, evidenced by a reduction in symptom severity of half or more.
“That represents a substantial increase over the 17% response rate seen with traditional antidepressants,” Zhang noted.
Upon analyzing the brain scans, researchers observed that among those receiving only standard care, a decline in activity within the cognitive control circuit correlated with a deterioration in problem-solving skills.
In contrast, the therapy group displayed a different trend: decreased activity was associated with improved problem-solving capabilities. The researchers believe this could be attributed to their brains learning to process information more effectively through therapy.
“We think they are now utilizing cognitive resources more efficiently, meaning they need less effort from the cognitive control circuit to achieve the same tasks,” Zhang explained.
Initially, these individuals were using excessive effort; now, they are working more intelligently.
On average, both groups showed improvement in depression severity. However, a closer examination of a 20-item depression assessment revealed that the symptom most relevant to cognitive control—”feeling everything is an effort”—benefited notably from the enhanced cognitive processing derived from the therapy.
“We are identifying improvements specifically tied to the cognitive aspects of depression, which significantly affect daily functioning,” Williams said.
Indeed, some participants mentioned that problem-solving therapy helped clear their thinking, enabling them to return to work, engage in hobbies, and navigate social settings more effectively.
Fast Track to Recovery
Just two months into the study, brain scans revealed changes in cognitive control circuit activity among the therapy participants.
“This is crucial because it indicates that tangible brain changes are occurring early, aligning with expected timelines for brain plasticity,” Williams remarked. “Real-world problem-solving is substantially altering the brain in just a few months.”
She added that the concept of thoughts and behaviors modifying brain circuits is not far removed from how exercising—a behavior—strengthens muscles.
The researchers found that these early adjustments were reliable indicators of which patients were responding to therapy, as well as likely to enhance problem-solving capabilities and alleviate depression symptoms even six months, twelve months, and one year post-therapy at the 24-month mark. This suggests that a brain scan could predict which patients are optimal candidates for problem-solving therapy.
This represents a move towards Williams’ vision of precision psychiatry—leveraging brain activity to align patients with the therapies that are most likely to aid them, thus accelerating their recovery.
“This is undoubtedly pushing the scientific boundaries,” Zhang stated. “But it is also set to transform many lives.”
Collaboration from researchers at the University of Washington, University of Pittsburgh School of Medicine, and The Ohio State University also contributed to this research.
Funding for the study came from the National Institutes of Health (grants UH2 HL132368, UH3 HL132368, and R01 HL119453).
