Scientists produce strongest evidence yet of schizophrenia's causes

An international team of scientists led by Cardiff University researchers has provided the strongest evidence yet of what causes schizophrenia - a condition that affects around 1% of the global population.

Published today (17:00BST, 03/06/2015) in the journal Neuron, their work presents strong evidence that disruption of a delicate chemical balance in the brain is heavily implicated in the disorder.

In the largest ever study of its kind, the team found that disease-linked mutations disrupt specific sets of genes contributing to excitatory and inhibitory signalling, the balance of which plays a crucial role in healthy brain development and function.

The breakthrough builds on two landmark studies led by members of the Cardiff University team, published last year in the journal Nature.

"We're finally starting to understand what goes wrong in schizophrenia," says lead author Dr Andrew Pocklington from Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.

"Our study marks a significant step towards understanding the biology underpinning schizophrenia, which is an incredibly complex condition and has up until very recently kept scientists largely mystified as to its origins.

"We now have what we hope is a pretty sizeable piece of the jigsaw puzzle that will help us develop a coherent model of the disease, while helping us to rule out some of the alternatives.

"A reliable model of disease is urgently needed to direct future efforts in developing new treatments, which haven't really improved a great deal since the 1970s."

Professor Hugh Perry, who chairs the Medical Research Council Neuroscience and Mental Health Board said: "This work builds on our understanding of the genetic causes of schizophrenia - unravelling how a combination of genetic faults can disrupt the chemical balance of the brain.

"Scientists in the UK, as part of an international consortium, are uncovering the genetic causes of a range of mental health issues, such as schizophrenia.

"In the future, this work could lead to new ways of predicting an individual's risk of developing schizophrenia and form the basis of new targeted treatments that are based on an individual's genetic makeup."

A healthy brain is able to function properly thanks to a precise balance between chemical signals that excite and inhibit nerve cell activity. Researchers studying psychiatric disorders have previously suspected that disruption of this balance contributes to schizophrenia.

The first evidence that schizophrenia mutations interfere with excitatory signalling was uncovered in 2011 by the same team, based at Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.