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Brain Scan Analysis Reveals Two Distinct Schizophrenia Subtypes

March 12, 2020

An analysis of brain scans from more than 300 patients suggests two distinct neuroanatomical subtypes of schizophrenia. Researchers published the findings online in the journal Brain.

“In the future, we’re not going to be saying, ‘This patient has schizophrenia.’ We’re going to be saying, ‘This patient has this subtype’ or ‘this abnormal pattern,’ rather than having a wide umbrella under which everyone is categorized,” said principal investigator Christos Davatzikos, PhD, the Wallace T. Miller Professor of Radiology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

brain scans graphic

The study involved 307 patients with schizophrenia and 364 healthy control subjects, age 45 or younger, from the United States, China, and Germany. Researchers analyzed brain scans of participants using a machine-learning method called HYDRA (Heterogeneity Through Discriminative Analysis), which is designed to identify disease subtypes by limiting the influence of age, sex, imaging protocols, and other confounding variables, the authors explained.

Olanzapine Use Associated With Change in Brain Structure

The analysis revealed two subtypes of schizophrenia. The first subtype showed lower widespread volumes of gray matter compared with healthy controls, a pattern historically linked with schizophrenia. However, 40% of patients with schizophrenia had a different pattern: gray matter volumes largely similar to healthy brains except for increases in brain volume in the striatum, an area of the brain involved in voluntary movement.

Researchers did not have an explanation for the variation.

“This is where we are puzzled right now,” Dr. Davatzikos said. “We don’t know. What we do know is that studies that are putting all schizophrenia patients in one group when seeking associations with response to treatment or clinical measures might not be using the best approach.”

—Jolynn Tumolo


Chand GB, Dwyer DB, Erus G, et al. Two distinct neuroanatomical subtypes of schizophrenia revealed using machine learning. Brain. 2020 February 27;[Epub ahead of print].

Researchers discover second type of schizophrenia [press release]. Philadelphia, Pennsylvania: University of Pennsylvania School of Medicine; February 26, 2020.

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