October 2017 Definitive International Study Reveals Schizophrenia is Associated with Widespread Change in Brain’s Wiring

 NUI Galway has co-led a major worldwide study with the University of Southern California showing that schizophrenia is associated with widespread changes in how the brain is wired. The study was published today (17 October 2017) in the major impact journal, Molecular Psychiatry.

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.”

The main focus of the study, co-led by Professor Gary Donohoe at the School of Psychology at NUI Galway, 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. Until now several small studies have tried to identify white matter changes with inconclusive results.

In an effort to overcome the problems of previous studies, researchers from around the world came together as part of the ‘ENIGMA consortium’ to carry out the first ever large-scale coordinated study of white matter microstructural differences in schizophrenia. In an unprecedented sample of 4,322 individuals scanned across 29 cohorts from Australia, Asia, Europe, South Africa and North America, data from patients and controls were re-analysed in a manner that allowed greater power to identify changes across the brain. The study also determined if disease-related factors (including duration of illness, age at onset of schizophrenia, antipsychotic medication, smoking, and severity of positive and negative symptoms) are also associated with differences in white matter microstructure.

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. While these differences were larger in some areas of the brain than others, an important finding from the study was that these changes were seen right across the brain and not just in one area. 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.

Commenting on the study, the studies’ senior author Professor Gary Donohue from NUI Galway, 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.”

Professor Donohoe added: “Schizophrenia can be enormously disabling and is frequently misunderstood. These studies are essential both for explaining the difficulties that those affected experience, but also to bring us further along the pathway to developing new therapies. Towards that end, 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.”

To read the full paper in Molecular Psychiatry, visit: http://www.nature.com/mp/journal/vaop/ncurrent/full/mp2017170a.html?foxtrotcallback=true

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