An international research team of neuroscientists says it has identified the clearest evidence to date, involving genes and brain chemistry, for the cause of schizophrenia.
Searching for an underlying cause, they say their findings strongly implicate the disruption of a delicate balance of chemicals inside the brain as a central factor in the mental disorder that affects about 1 percent of the world's population.
That disruption is the result of disease-linked mutations affecting specific groups of genes involved in excitatory and inhibitory signaling, the balancing of which in a healthy brain plays a vital role in development and function, they report in the journal Neuron.
Their conclusion comes after an analysis of genetic data from 11,355 schizophrenia patients, compared with a control group of 16,416 people not suffering from the disorder.
They focused on a kind of mutation known as copy number variants, or CNVs, in which significant strings of DNA are either missing or have been duplicated.
Such mutations in persons suffering from schizophrenia tended to affect genes responsible for certain particular aspects of brain function, they discovered.
The finding "marks a significant step towards understanding the biology underpinning schizophrenia," says lead author Dr. Andrew Pocklington from Cardiff University in Wales. "We're finally starting to understand what goes wrong in schizophrenia."
Proper functioning in a healthy brain is down to a precise balance between the brain chemicals involved in exiting and inhibiting nerve cell activity, the researchers explain.
In two studies published last year in the journal Nature, Cardiff researchers had first suggested the schizophrenia might involve genetic mutations that interfere with how those chemical signals operate, based on work begun in 2011.
While the fact that schizophrenia often runs in families has always suggested a genetic component to the disorder, the exact mutation mechanism has been difficult to ascertain before now, the researchers note.
"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," says Hugh Perry, chair of the Neuroscience and Mental Health Board of the UK's Medical Research Council.
The researchers, noting that CNV's are thought to be involved in other neurodevelopment disorders like autism spectrum disorder and ADHD, say their findings could have worth to researchers in a number of areas of neuroscience.
Schizophrenia can result in extremely disruptive symptoms including delusions, hallucinations and behavioral changes that can negatively affect a sufferer's ability to lead a normal life, experts say.