Depression has many faces. Some people can’t sleep, while others struggle to get out of bed. Even though symptoms and severity can vary from person to person, a recent study found that a specific brain circuit might be associated with the mental malady.
Located in the prefrontal cortex, the brain’s cognitive control circuit plays a part in our attention, goal-setting behavior and other executive functioning. Depression often impairs these functions, and psychiatrists have developed non-pharmacological therapies such as cognitive behavioral therapy to address these problems. Capturing this circuit’s activity might eventually help psychiatrists predict the course of someone’s depression.
The results of a randomized controlled trial published in Science Translational Medicine confirmed this association, finding that problem-solving therapy and weight loss interventions improved executive functioning and attention. Just as weight training can strengthen a weak muscle, this therapy boosts the brain’s cognitive function. And when the researchers analyzed study participants’ early brain scans using machine learning, it accurately predicted changes in future depression symptoms.
“Our study provides proof that, indeed, problem-solving therapy can modulate underlying neural mechanisms to improve problem-solving ability and depression symptoms,” said lead author Xue Zhang, a neuroimaging scientist at Stanford University.
Zhang hopes that identifying regions of the brain like the cognitive control circuit can add to the emerging field of precision medicine and help psychiatrists tailor their depression treatments based on an individual’s neural makeup, rather than the current, pharmacological-shotgun approach.
The findings are welcome news for psychiatrists, who are desperate for effective treatments. Depression is already the world’s leading cause of disability, affecting 320 million people or nearly equivalent to the United States population. But recent reviews and meta-analyses of antidepressant drugs — the most common treatment — have found that the drugs’ success is often due to the placebo effect. Depression treatment is further complicated and resistant to therapy with comorbid obesity.
The study included 108 participants, skewing heavily towards non-hispanic white women. The experimental group included 59 people, who received enhanced care such as problem-solving therapy for depression and weight management advice and regular meetings with a life coach. By contrast, the control group received basic advice for weight loss and some of them received psychotropic medications.
Researchers scanned participants’ brains using functional MRI while participants completed a button-pressing task that aimed to measure impulsiveness. The therapy occurred five times — at baseline, two months, six months, 12 months and 24 months.
The study showed how early changes in the 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 at two months could help identify patients who are less likely to respond to a specific treatment, giving clinicians an early opportunity to consider other interventions.
While the findings will need to be replicated in a more representative sample, the data have Zhang dreaming of the findings’ clinical applications, especially after some of her colleagues also demonstrated the cognitive control circuit’s role in depression.
“We have shown that this [therapy] can modulate the cognitive control circuit to improve treatment outcome,” she said. “It’s the first step to 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 participants, they found that the technology reliably captured the same information.
Psychologist Pim Cuijpers is quick to pump the brakes about any conclusions made using the fMRI data.
“It is completely logical that circuits in the brain are changed because of depression and when the depression gets better, then the brain circuits also get better,” said Cuijpers, a professor emeritus at Vrije Universiteit Amsterdam. “In order to show that there is a causal mechanism, much more is needed.”
Other experts such as Charles Lynch were excited by the paper’s ability to capture longitudinal data, rather than grabbing individual snapshots.
“As a field, we have often relied on relatively simple “pre-to-post” comparisons for evaluating the effects of an intervention like this,” said Lynch, a psychiatrist at Weill Cornell Medical in New York City. “What is really nice and unique about this study is that they measured activity in the brain circuitry targeted by the behavioral intervention five times over two years, which allowed them to identify early brain predictors of response at later time points.”
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