Tests for various substances in the blood are one example of the power of “biomarkers,” measurable biological traits that tell doctors a patient either has or is at risk for a particular illness. While such tests so far have mostly eluded psychiatry, a large new brain-scan study identified four categories of biological activity, or “biotypes,” of depression that may help doctors choose more effective treatments – just as a blood test might guide treatment of a cancer or heart disease.

When researchers used a machine learning program to divide over 450 depression patients into categories based on biomarkers in their brain activity patterns, they found four categories associated with distinct sets of clinical symptoms, according to their report in the journal Nature Medicine.

Strikingly, patients in one of these four categories were about three times more likely to respond to a noninvasive treatment known as transcranial magnetic stimulation (TMS) than patients in two of the other categories. TMS is a therapy in which magnetic fields stimulate specific regions of the brain, and has been particularly useful in cases of treatment-resistant depression.

Many of the scientists on the team have received support from the BBRF during their careers. The lead investigator on the study, Conor Liston, M.D., is a Young Investigator grantee of 2013. The same award was conferred upon contributors Desmond Jay Oathes, Ph.D., in 2016; Amit Etkin, M.D., Ph.D., in 2012; Jennifer Keller, Ph.D., in 2009; Helen S. Mayberg, M.D., in 1991; and Marc J. Dubin, M.D., Ph.D., in 2010. Dr. Mayberg received an Independent Investigator grant in 1995, as did Alvaro Pascual-Leone, M.D., Ph.D., in 1998, and a Distinguished Investigator grant in 2002. Dr. Mayberg also serves on the BBRF’s Scientific Council, along with 2005 Falcone Prizewinner Alan F. Schatzberg, M.D., and 2015 Ruane Prizewinner BJ Casey, Ph.D.

The team used functional magnetic resonance imaging (fMRI), a type of noninvasive brain scan that measures brain activity, to look for patterns in patients’ brains while in the “resting state”—the brain’s state of activity when not engaged in a conscious task, like reading. They examined how 258 different brain areas interacted with one another while in the resting state, and these brain circuit-level differences revealed four biotypes of depression.

Brains of patients who had depressive anxiety tended to have fewer connections in the brain networks involved in responses to fear and negative emotional stimuli. Those with difficulty feeling pleasure, a condition called anhedonia, had more connections in networks that regulate reward processing and control over movement.

Noting that “biomarkers have already transformed the diagnosis and management of cancer, diabetes, heart disease and even pain syndromes,” the researchers express hope that the biotypes they have identified will allow doctors to more specifically diagnose depression and determine the most effective treatment plan.