Schizophrenia linked with change in brain’s wiring

Schizophrenia associated widespread change brain’s wiring nui Galway study
Science Conferring at NUI Galway. Photograph by Aengus McMahon

A major worldwide study co-led by NUI Galway has found that schizophrenia is associated with widespread changes in how the brain is wired.

The main focus of the study, co-led by Professor Gary Donohoe at the School of Psychology at NUI Galway in conjunction with the University of Southern California, was to identify changes in white matter, often thought as the brain’s wiring system that causes this disability.

Cumulative evidence has led to a ‘dysconnectivity’ hypothesis that schizophrenia may involve abnormal or inefficient communication between brain regions, due to disturbances in the underlying pattern of white matter.

It was the first-ever large-scale coordinated study of white matter microstructural differences in schizophrenia.

Until now several small studies have tried to identify white matter changes with inconclusive results, which saw researchers come together from around the world as part of the ‘ENIGMA consortium’.

The study involved an unprecedented sample of 4,322 individuals scanned across 29 cohorts from Australia, Asia, Europe, South Africa and North America.

Definitive proof

Professor Gary Donohue, said: “It’s almost 40 years since we had the first clues that schizophrenia was associated with changes in brain structure.

“What the ENIGMA consortium has achieved here is to provide definitive proof that these changes are not specific to any one area of the brain, but rather reflect subtle yet widespread changes throughout the brain.

“In terms of the idea that schizophrenia might be caused by a mis-wiring of the brain, this study provides unequivocal evidence that this is the case. The next steps will be to identify the individual genetics variants that lead to this mis-wiring.”

Using an approach known as diffusion tensor imaging, or DTI, the results from the study showed that throughout the brain, the so-called ‘white matter’ fibres which connect different brain regions are slightly altered, or frayed, making communication between different brain regions sub-optimal.

Schizophrenia associated widespread change brain’s wiring nui Galway study
Image of the human brain. Photo NUI Galway

In schizophrenia, these changes are likely to help explain several clinical symptoms such as hallucinations and delusions, but also the cognitive difficulties that people experience and that strongly predict a level of disability.

Professor Donohoe added: “….this study is pointing us in a particular direction to treat schizophrenia as a disorder affecting the whole brain rather than one part of it.”

Schizophrenia is a debilitating psychiatric disorder with a considerable societal burden and has been a major focus of neuroimaging studies for decades, yet its neurobiology remains only partially understood.

The World Health Organisation has described schizophrenia as a “leading cause of disability, and more disabling that paraplegia or blindness in 18-35 year olds.”

To read the full paper in Molecular Psychiatry, visit:

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