Brain imaging analysis shows schizophrenia is more than a single disorder

By John Murphy, MDLinx
Published October 15, 2015

Key Takeaways

Researchers have gathered evidence to show that schizophrenia is not a single disorder but rather a variety of disorder subgroups. The findings, published online October 15, 2015 in NeuroImage, could be a step toward individualizing diagnosis and personalizing treatment of schizophrenia, the researchers suggest.

“By looking at the brain’s anatomy, we’ve shown there are distinct subgroups of patients with a schizophrenia diagnosis that correlate with symptoms,” said senior investigator C. Robert Cloninger, MD, PhD, the Wallace Renard Professor of Psychiatry and a professor of genetics at Washington University School of Medicine in St. Louis, MO. “This gives us a new way of thinking about the disease. We know that not all patients with schizophrenia have the same issues, and this helps us understand why.”

Other research has attempted to use brain imaging and analysis to study white matter in hopes of corresponding abnormalities to schizophrenia, but findings have been inconsistent.

In this investigation, researchers evaluated diffusion-weighted magnetic resonance imaging (MRI) scans in 47 people diagnosed with schizophrenia and 36 healthy volunteers. Next, they incorporated a purely data-driven and unbiased “unsupervised machine learning approach” to decompose the images from different schizophrenia patients into clusters.

“We didn’t start with people who had certain symptoms and then look to see whether they had corresponding abnormalities in the brain,” said corresponding author Igor Zwir, PhD, an instructor in psychiatry at Washington University and an associate professor in the Department of Computer Science and Artificial Intelligence at the University of Granada, Spain. “We just looked at the data, and these patterns began to emerge.”

What emerged were clusters that mapped directly onto specific brain structures in portions of the corpus callosum, a structure considered critical to neural communication. When the researchers looked at these abnormalities across the corpus callosum, they found that certain characteristics revealed in the brain scans matched specific symptoms of schizophrenia.

For example, patients with specific features in one part of the corpus callosum typically displayed bizarre and disorganized behavior. In other patients, irregularities in a different part of that structure were associated with disorganized thinking and speech, and symptoms such as a lack of emotion. Other brain abnormalities in the corpus callosum were associated with delusions or hallucinations.

“This kind of granular information, combined with data about the genetics of schizophrenia, one day will help physicians treat the disorder in a more precise way,” Dr. Zwir said.

In 2014, the same team of researchers reported evidence that distinct sets of genes were strongly associated with particular clinical symptoms, which suggested that schizophrenia is not a single disease but a group of 8 genetically distinct disorders, each with its own set of symptoms.

“We’ve shown that there are distinct subgroups among people with schizophrenia, and they differ in terms of networks of genes, specific brain structures, and different clinical syndromes,” Dr. Cloninger said.

“Our results may provide clues about distinct pathophysiological processes that produce different forms of schizophrenia,” the authors concluded. “This approach may be a pioneering contribution towards a foundation for precise person-centered diagnosis and treatment of psychotic disorders.”

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