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Genetics study helps explain causes of schizophrenia

8 June 2015
Appeared in BioNews 805

New research into schizophrenia has identified genetic mutations in patients which affect the balance between chemical signalling systems in the brain.

The findings have been described as the 'strongest evidence yet' of what causes the condition, and could lead to a basis for further understanding of how it develops.

'We're finally starting to understand what goes wrong in schizophrenia,' said Dr Andrew Pocklington, of Cardiff University and a lead author of the study. '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.'

In the study, published in Neuron, scientists looked at the genetic code of 11,355 patients with schizophrenia and compared them with 16,416 people without the condition.

They looked at mutations called copy number variants (CNVs), where long sequences of DNA are duplicated or deleted. CNV mutations have been implicated in schizophrenia before and are also thought to contribute to other conditions such as ADHD and autism.

They found that the genes affected by this type of mutation were involved in the ways by which signals are passed between nerve cells in the brain.

Different chemical systems are used to carry 'excitatory' signals, which increase a cell's signalling activity, and 'inhibitory' systems, which cause a decrease in activity. A balance between these major systems is necessary for correct brain development and function.

Previous work by the group showed that the excitatory systems were affected in schizophrenia. The current research confirmed these findings and showed genetic evidence for the first time that the inhibitory systems are also involved in causing the condition.

The team says that the effects on both systems disrupt the balance between them and could be behind the symptoms and development of schizophrenia. They write that their findings provide 'firm foundations for studies aimed at dissecting disease mechanisms'.

'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,' said Professor Hugh Perry, chair of the Medical Research Council's Neuroscience and Mental Health Board.

Schizophrenia can give rise to a variety of symptoms, including changes in behaviour and thought, hallucinations and delusions. It is estimated that one in 100 people will experience schizophrenia over their lifetime.

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