Scientists say they’ve found neurological evidence of four different subtypes of depression—a discovery that may someday help doctors select the best treatment for their depressed patients. The research was published in the journal Nature Medicine.

Depression is an exceptionally slippery beast. Unlike ailments located elsewhere in the body, mental illnesses are classified and diagnosed not by concrete physical signs, or biomarkers, but by patients’ behavior. There are a lot of problems with this approach, including the fact that a lot of different illnesses can cause the same symptoms—and that the same illness can cause different symptoms in different people.

What we call “depression” is an experience that likely has many different causes, co-author Conor Liston of Weill Cornell Medical College told scientific American. “The fact that we lump people together like this has been a big obstacle in understanding the neurobiology of depression.”

Liston and his colleagues analyzed functional magnetic resonance imaging (fMRI) scans from 17 different research sites around the world. They took in scans from 1188 people, about 40 percent of whom had depression, and were able to look closely at an astounding 258 brain regions in each person.

The team had expected to find some differences between the brains of people with depression and without. They found those, but they also found differences within the group of depressed people. Differences in brain activity and connectivity revealed four distinct subtypes among people with depression.

Most excitingly, these brain-activity subtypes matched up with different medical profiles. Patients in subtypes 1 and 2 described feeling more fatigue, while people in subtypes 3 and 4 had trouble feeling pleasure.

The subtypes also responded differently to treatment techniques. People in subtype 1, for example, were more likely to experience relief with transcranial magnetic stimulation (TMS), a non-pharmaceutical method that uses electromagnetic impulses to stimulate a sluggish brain.

More research is needed, but these findings are both heartening and promising, Liston says. Depression “is not just one biological thing.”


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