December 11, 2023

Scientists at Stanford University have identified a major biological mechanism behind major depressive disorder and shown how to treat it. In people with depression, signals between two key parts of the brain appear to flow the wrong way, but magnetic stimulation can reverse them, leading to a dramatic improvement in symptoms.

In recent decades, scientists have developed a non-invasive way to induce electrical activity in specific parts of the brain. The process, known as transcranial magnetic stimulation (TMS), has been shown to have a wide range of benefits, from enhancing memory to reducing phobias, food cravings or drug addiction.

One of the most promising uses is in the treatment of depression. In a 2020 pilot study, an approach called Stanford Neuromodulation Therapy (SNT) achieved an incredible 90% remission rate in patients with severe treatment-resistant depression. But exactly how magnetic stimulation works in the brain to reduce depressive symptoms remains unknown.

Now the team has an answer. The researchers analyzed fMRI data from 33 people with treatment-resistant major depressive disorder and compared it to scans from 85 people without depression. They found major differences in how the two brain regions communicate.

The anterior insula is a brain region responsible for receiving sensations such as pain, taste or temperature and helping to regulate subjective emotions accordingly. It does this by sending signals to another area, called the anterior cingulate cortex, which is responsible for controlling emotions.

However, scientists at Stanford University found that in about 75 percent of people with depression, this communication happens in reverse—the anterior cingulate cortex sends signals to the anterior insula, and the higher the proportion of the reverse signal, the more severe the depression.

“What we’ve seen is that who’s the sender and who’s the receiver in a relationship seems to be very important in whether or not a person is depressed,” said Anish Mitra, lead author of the study. “It’s as if you have decided how you feel, and then everything you feel is filtered out. Mood comes first. This is consistent with what many psychiatrists think about depression. Saying very happy things suddenly doesn’t bring them any joy.”

Over a period of five days, the team administered SNT to 23 of 33 depressed patients, while 10 received a placebo. Within three days of treatment ending, the flow of signals between these two brain regions was corrected, and patients reported an improvement in their mood. The more severe the depression, the greater the improvement.

Nolan Williams, the study’s senior author, said: “In the field of psychiatry, this is the first time that this particular change in biology — the flow of signals between these two brain regions — to predict changes in clinical symptoms.” “fMRI data that allow for precise treatment using SNT can be used both as a biomarker for depression and as a personalized, targeted approach to treating its underlying cause. When we find a patient with When we look at people with severe depression, we can look for this biomarker to determine how likely they are to respond well to SNT treatment.”

The researchers now plan to trial the technique in a larger patient cohort.The study was published in the journal Proceedings of the National Academy of Sciences.

source: Stanford University