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The symptoms of schizophrenia vary greatly from person to person. A new study shows how these differences manifest themselves in the structure of the brain.
Schizophrenia is a complex mental health condition that affects perception, thought and emotions. This complexity is reflected in the individual manifestations of the disease: for some patients, perceptual disturbances are the main problem, while for others, cognitive impairments are more prevalent. “In this sense, there is not one schizophrenia, but many, each with different neurobiological profiles,” says Wolfgang Omlor, first author of the study and senior physician at the University Hospital of Psychiatry Zurich.
To do justice to each of these types of schizophrenia, a precision medicine approach would have to be adopted – for example, with therapies that precisely match the respective neurobiological profile. “This requires approaches that look for both individual differences and similarities at the neurobiological level,” explains Omlor.
Comprehensive international study of patients’ brain structures
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.
Less flexible brain development in early childhood revealed
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.”
Prof. Dr. med. univ. Philipp Homan, PhD
Department of Adult Psychiatry and Psychotherapy
University of Zurich and Psychiatric University Hospital Zurich
+41 58 384 33 65
philipp.homan@bli.uzh.ch
Dr. med. Dr. sc. nat. Wolfgang Omlor
Department of Adult Psychiatry and Psychotherapy
University of Zurich and Psychiatric University Hospital Zurich
+41 58 384 2111
wolfgang.omlor@bli.uzh.ch
Wolfgang Omlor, Finn Rabe, et al., Philipp Homan. Estimating Multimodal Structural Brain Variability in Schizophrenia Spectrum Disorders: A Worldwide ENIGMA Study. Am J Psychiatry 2025; 0:1–16; DOI: 10.1176/appi.ajp.20230806
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