Stanford scientists have discovered a major biological mechanism behind severe depression, and shown how to treat it. Signals between two key parts of the brain seem to flow the wrong way in people with depression, but magnetic stimulation reverses them, drastically improving symptoms.
In recent decades scientists have developed a non-invasive method of inducing electrical activity in specific parts of the brain. Known as transcranial magnetic stimulation (TMS), this process has been shown to have a wide range of benefits, from boosting memory to reducing phobias, food cravings or drug addiction.
One of the most promising uses has been in treating depression. In 2020 a preliminary study, a method called the Stanford Neuromodulation Therapy (SNT) achieved an incredible 90% remission rate in people with severe, treatment-resistant depression. But exactly how the magnetic stimulation was working in the brain to alleviate depression symptoms remained unknown.
Now the team has found an answer. The researchers analyzed fMRI data of 33 patients with treatment-resistant major depressive disorder, and compared them to scans from 85 people without depression. And they found a crucial difference in the way two brain regions communicated.
The anterior insula is a brain region that takes in sensation, such as pain, taste or temperature, and helps regulate subjective emotions accordingly. This it does by sending signals to another region, called the anterior cingulate cortex, which governs emotions.
However, the Stanford scientists found that in around 75% of the patients with depression, this communication was happening backwards – the anterior cingulate cortex was sending signals to the anterior insula, with higher proportions of reverse signals correlating with more severe depression.
“What we saw is that who’s the sender and who’s the receiver in the relationship seems to really matter in terms of whether someone is depressed,” said Anish Mitra, lead author of the study. “It’s almost as if you’d already decided how you were going to feel, and then everything you were sensing was filtered through that. The mood has become primary. That’s consistent with how a lot of psychiatrists see depression. Even things that are quite joyful to a patient normally are suddenly not bringing them any pleasure.”
Over five days, the team administered SNT to 23 of the 33 patients with depression, with the other 10 receiving a placebo treatment instead. Within three days of the end of treatment, the flow of signals between these two brain regions was corrected, and patients reported an improvement to their mood. The more severe the depression, the greater the improvement.
“This is the first time in psychiatry where this particular change in a biology – the flow of signals between these two brain regions – predicts the change in clinical symptoms,” said Nolan Williams, senior author of the study. “The fMRI data that allows precision treatment with SNT can be used both as a biomarker for depression and a method of personalized targeting to treat its underlying cause. When we get a person with severe depression, we can look for this biomarker to decide how likely they are to respond well to SNT treatment.”
The researchers now plan to trial the technique in a bigger group of patients. The research was published in the journal Proceedings of the National Academy of Sciences.
Source: Stanford University