Depression Severity Now Detectable With Biomarkers

Stanford researchers have revealed how severe depression actually works.

Depression is generally understood to be caused by an imbalance in brain chemicals, which, although a simplified way of understanding depression, is enough to understand why it happens. Transcranial magnetic stimulation (basically using a powerful magnetic source near the scalp to alter brain function) has been used to provide relief to severely depressed individuals for many years.

Now medical researchers at Stanford have figured out how TMS (transcranial magnetic stimulation) works. It works not by inducing electric currents in the brain, instead, this treatment for depression works by the abnormal signals in the brain having their directions reversed. 

Anish Mitra, MD, Ph.D. said he was sceptical of the common understanding of TMC that it changed the “flow of neural activity” and hence wanted to test what TMC actually did. Fortunately, he had just the tool for it. When Mitra was a graduate student at Washington University, he developed a mathematical tool to analyze fMRI which is usually used to detect active areas of the brain.

The study

Analysis of treatment for patients with depression
Analysis method and differences in fMRI lag structure between active and sham SNT.

The study published on May 15th chose the FDA-cleared ‘Stanford neuromodulation therapy’ (SNT) – a faster form of TMS working with just 10 sessions each day for 5 days instead of daily sessions over several weeks or months. Both TMS and SNT are only administered to patients with depression so severe that can’t be cured with medication or therapy.

33 patients were chosen for the study, 10 of which were treated with a procedure that mimics SNT but without any magnetism as a placebo. The results of these 33 individuals were later compared with 85 individuals without depression working as the control group.

The fMRI data showed a single connection of interest. In the brain of individuals with no depression, the anterior insula (the region concerned with bodily sensations) sends signals to the anterior cingular cortex (the region concerned with emotions). The anterior cingular cortex received the information from the anterior insula (like heart rate or body temperature) and then decides how to feel about these signals.

This flow of signals, however, was reversed in about three-quarters of the participants with depression. “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,” Mitra, lead author of the study, said. How the person feels seems to dictate what the body does in people with depression.

This observation is consistent with how many psychiatrists understand depression. How the person feels (i.e., depressed) shapes their entire life. Even things that are supposed to bring joy to the person normally will have little to no effect on them in this state.

Patients with depression when treated with SNT showed a shift in their flow of neural activity back to the normal direction within a week. This shift coincides with the patients’ depression being lifted after the treatment period.

Depression is a challenge to treat because it lacks insight into how it works biologically. Unlike a fever, which can be tested for various bacterial or viral infections which helps find the appropriate treatment, Depression has no such tests to find appropriate treatments.

Not everyone with depression has this abnormal flow of neural activity, and it may be even rarer in less severe cases, but it could serve as an important biomarker to detect more appropriate and effective treatment for depression. The fMRI which is used in SNT for precision can be used to identify these biomarkers. These fMRI scans can also be used to check how likely a patient is to respond well to SNT. 

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