6,000 Brain Scans Reveal the Many Faces of Schizophrenia

Researchers analyzed thousands of brain scans to uncover how schizophrenia varies at a structural level. While some brain areas differ greatly between patients, others share a common developmental trait, suggesting early brain formation plays a key role.

Schizophrenia affects people in many different ways, and a new study reveals that these variations are reflected in brain structure.

As a complex mental health condition, schizophrenia impacts perception, thinking, and emotions in diverse ways. Some individuals experience severe perceptual disturbances, while others struggle more with cognitive impairments. “In this sense, there is not one schizophrenia, but many, each with different neurobiological profiles,” explains Wolfgang Omlor, the study’s first author and a senior physician at the University Hospital of Psychiatry Zurich.

Treating schizophrenia effectively may require a precision medicine approach, where therapies are tailored to an individual’s specific neurobiological profile. “This requires approaches that look for both individual differences and similarities at the neurobiological level,” says Omlor.

Examining Brain Structure on a Global Scale

In an international multicenter study, Wolfgang Omlor and the research team at the University of Zurich examined the variability of brain structure in patients with schizophrenia: Which brain networks show a high degree of individuality and which a high degree of similarity? The researchers examined several characteristics, including the thickness and surface area of the cerebral cortex, as well as the folding pattern and volume of deeper brain regions.

The data was taken from the ENIGMA collaboration, an international research project that combined imaging data from more than 6,000 people in 22 countries. By comparing the brain structures of several thousand patients with schizophrenia and healthy individuals, the variability of brain structure could be studied with a high degree of reliability.

Early Brain Development and Its Lasting Impact

While variable brain structures in schizophrenia may reflect differences in symptoms between patients, the uniformity of brain folding in the mid-frontal brain area suggests a developmental trait common to people with schizophrenia. Because brain folding is largely completed in early childhood, brain development during this period appears to be less flexible in schizophrenia patients, particularly in areas responsible for linking thinking and feeling processes.

“These findings broaden our understanding of the neurobiological basis of schizophrenia,” says Philipp Homan professor at the University of Zurich and corresponding author of the study. “While uniform brain folding may indicate possible mechanisms of disease development, regions with high variability in brain structure may be relevant for the development of individualized treatment strategies.”

Reference: “Anticholinergic Burden and Cognitive Function in Psychosis: A Systematic Review and Meta-Analysis” by Valentina Mancini, Caren Latreche, Jack B. Fanshawe, Ioana Varvari, Chambrez-Zita Zauchenberger, Nova McGinn, Ana Catalan, Toby Pillinger, Philip K. McGuire and Robert A. McCutcheon, 26 February 2025, American Journal of Psychiatry.