Depression has many faces. Some people can’t sleep, while others have trouble getting out of bed. Although symptoms and severity can vary from person to person, a recent study found that a specific brain circuit may be linked to the mental illness.
The brain’s cognitive control circuitry, located in the prefrontal cortex, plays a role in our attention, goal setting, and other executive functioning. Depression often impairs these functions, and psychiatrists have done so as well developed non-pharmacological therapies such as cognitive behavioral therapy to address these problems. Capturing the activity of this circuit could ultimately help psychiatrists predict the course of a person’s depression.
The results of a randomized controlled trial published in Science Translational Medicine confirmed this connection and found that problem-solving therapy and weight loss interventions improved executive functioning and attention. Just as strength training can strengthen a weak muscle, this therapy stimulates the cognitive function of the brain. And when the researchers plugged the study participants’ early brain scans into a large language model, it accurately predicted changes in future depression symptoms.
“Our study provides evidence that problem-solving therapy can indeed modulate the underlying neural mechanisms to improve problem-solving ability and depression symptoms,” said lead author Xue Zhang, a psychiatrist at Stanford University.
Zhang hopes that identifying areas of the brain, such as the cognitive control circuit, can contribute to the emerging field of precision medicine and help psychiatrists tailor their depression treatments to an individual’s neural makeup, rather than the current pharmacological approach.
The findings are welcome news for psychiatrists, who are desperate for effective treatments. Depression is already it the world’s leading cause of disabilityaffecting 320 million people, or nearly the equivalent of the population of the United States. But recent reviews And meta-analyses of antidepressants – the most common treatment – have found that the drugs’ success is often due to the placebo effect. Treating depression becomes even more complicated resistant to therapy with comorbid obesity.
The study included 108 participants, which skew heavily toward non-Hispanic white women. The experimental group consisted of 59 people, who received enhanced care such as problem-solving therapy for depression and advice on weight management and regular meetings with a life coach. In contrast, the control group received basic weight loss advice and some of them were given psychotropic medications.
Researchers scanned participants’ brains using functional MRI while participants completed a button-pressing task aimed at measuring impulsivity. Therapy took place five times: at baseline, two months, six months, twelve months and 24 months.
The study showed how early changes in cognitive control circuit activity could be useful in predicting how a patient might respond to treatment at six, 12 and 24 months. The study data suggests that circuit changes observed after two months may help identify patients who are less likely to respond to a specific treatment, giving clinicians an early opportunity to consider other interventions.
Although the findings will need to be replicated in a more representative sample, the data has Zhang dreaming of clinical applications of the findings, especially after some of her colleagues also did the role of the cognitive control circuit in depression.
“We have shown this [therapy] can modulate the cognitive control circuitry to improve treatment outcomes,” she said. “It is the first step toward using fMRI to help make clinical decisions.”
When asked about the reliability of fMRI scans to study the brain, Zhang acknowledged that the technology is fickle. Skepticism is warranted, she said, but when the team rescanned the participants, they found that the technology reliably captured the same information.
Psychologist Pim Cuijpers quickly slows down when conclusions are drawn based on the fMRI data.
“It makes perfect sense that circuits in the brain change as a result of depression and if the depression gets better, the brain circuits also get better,” says Cuijpers, professor emeritus at the Vrije Universiteit Amsterdam. “Much more is needed to demonstrate that a causal mechanism exists.”
Other experts, such as Charles Lynch, were enthusiastic about the paper’s ability to capture longitudinal data, rather than taking individual snapshots.
“As a field, we have often relied on relatively simple ‘pre-to-post’ comparisons to evaluate the effects of an intervention like this,” says Lynch, a psychiatrist at Weill Cornell Medical in New York City. “What’s really fun and unique about this study is that they measured activity in the brain circuits targeted by the behavioral intervention five times over two years, allowing them to identify early brain predictors of response at later time points.”