Second Type of Neuroanatomical Schizophrenia Discovered


This cohort included 307 patients with schizophrenia and 364 healthy controls who were 45 years old and younger.

Two distinct neuroanatomical subtypes of schizophrenia were discovered after analyzing the brain scans of more than 300 patients, according to a study conducted by Penn Medicine. The first type showed lower widespread volumes of gray matter compared with healthy controls, whereas the second type had volumes largely similar to normal brains. The findings suggest that accounting for these differences could inform more personalized treatment options in the future, according to the study authors.

Researchers at Penn Medicine spanned their schizophrenia patient population across 3 continents—the United States, China, and Germany. This cohort included 307 patients with schizophrenia and 364 healthy controls who were 45 years old and younger.

Brain scans were analyzed by the research team using the machine learning method Heterogeneity Through Discriminative Analysis (HYDRA) to help identify “true disease subtypes” by limiting the influence of confounding variables, such as age, sex, imaging protocols, and other factors, according to the study authors.

After applying HYDRA to the brain images, the researchers discovered that 115 patients with schizophrenia did not have the typical pattern of reduced gray matter volume that is historically linked to the disorder. These patients showed increases of brain volume in the middle of the brain in the striatum, which plays a role in voluntary movement. However, when controlling the differences in medication, age, and other demographics, the researchers could not find any clear explanation for the variation.

“The treatments for schizophrenia work really well in a minority of people, pretty well in most people, and hardly at all in a minority of people. We mostly can’t predict that outcome, so it becomes a matter of trial and error,” co-senior author Daniel Wolf, MD, PhD said in a press release. “Now that we are starting to understand the biology behind this disorder, then we will hopefully one day have more informed, personalized approaches to treatment.”

Future research will provide a more detailed picture of these schizophrenia subtypes in relation to other aspects of brain structure and function, clinical symptoms, disease progression, and etiology, according to the study authors.


Researchers discover second type of schizophrenia. Penn Medicine News. Published February 27, 2020. Accessed April 15, 2020.

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