The disease-linked mutations observed by the researchers affect the balance of chemicals in the brain that regulate nerve cell activity.
The mutations disrupt genes that regulate excitatory and inhibitory neurotransmission, which needs to be delicately balanced to ensure the brain functions properly.
"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," says lead author Dr. Andrew Pocklington of Cardiff University, Wales.
"We now have what we hope is a pretty sizable 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."
Experts have known for some time that schizophrenia is a highly heritable disorder. While schizophrenia occurs in 1% of the general population, it occurs in 10% of people who have a first-degree relative with the condition. The identical twin of someone with schizophrenia has a 40-65% chance of developing the disorder themselves.
The healthy functioning of a brain is dependent on the balance between chemical signals that regulate the activity of nerve cells. In the past, psychiatric disorder experts have suggested that disruption of this balance could contribute to the development of schizophrenia.
In 2011, the authors - based at Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics - found evidence that schizophrenia mutations interfere with excitatory chemical signaling.
Their new study, published in Neuron, not only confirms these findings but also provides strong evidence that the disruption of inhibitory signaling also contributes to schizophrenia.
Mutations may contribute to other disorders such as autism spectrum disorder
For the study, the team compared the genetic data of 11,355 people diagnosed with schizophrenia with data for 16,416 people without the disorder. These data were obtained from three separate studies: the International Schizophrenia Consortium, the Molecular Genetics of Schizophrenia and a UK-based study of patients with schizophrenia taking an antipsychotic drug.
The researchers examined the genetic data, searching specifically for types of mutation referred to as copy number variants (CNVs) - mutations whereby large stretches of DNA are either missing or multiplied.
CNVs in the participants with schizophrenia typically disrupted genes that were involved in neurotransmission in the brain, compared with CNVs found in people without the disorder. The findings indicate that disruption of this signaling is of direct causal relevance.
These mutations are also believed to be implicated in the development of other neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
"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," says Prof. Hugh Perry, chair of the Medical Research Council Neuroscience and Mental Health Board in the UK.
"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."
Previously, Medical News Today reported on a Canadian study that found immigrants from Bermuda and the Caribbean and refugees from East Africa and South Asia are up to two times as likely to develop psychotic disorders in comparison with the general population.