Researchers believe they have solved a riddle that has challenged scientists for more than 70 years – how the brain chemical dopamine relates to schizophrenia.
The brain disorder is characterised by delusional thinking, hallucinations and other forms of psychosis.
According to the study, there is physical evidence that cells in the nervous system (neuronal cells) are unable to precisely control levels of dopamine.
Scientists also identified the genetic mechanism that controls the dopamine flow.
Daniel Weinberger, chief executive and director of the Lieber Institute in America and co-author of the study, said: “Until now, scientists have been unable to decipher whether the dopamine link was a causative factor or solely a way to treat schizophrenia.
“We have the first evidence that dopamine is a causative factor in schizophrenia.”
Dopamine acts as a chemical messenger that sends signals between neurons – nerve cells in the brain – to change their activity and behaviour.
The chemical is the reward neurotransmitter that enables people to feel pleasure.
According to the World Health Organisation, the condition affects one in 300 people worldwide.
Symptoms typically start in late adolescence or early adulthood, although cognitive impairment and unusual behaviour sometimes appear in childhood.
Current treatments include antipsychotic drugs that address the symptoms of psychosis, but not the cause.
Dr Jennifer Erwin, an investigator at the institute and one of the authors on the report, said: “One of the major side effects of the drugs used to treat schizophrenia is lack of pleasure and joy.
“In theory, if we could target the dopamine receptor specifically with drugs, that could be a new strategy for treatment that would not limit a patient’s joy as much.”
For years scientists have known that irregular levels of dopamine have some connection to psychosis and are a critical factor in schizophrenia, Alzheimer’s disease and other neuropsychiatric disorders.
Drugs that increase dopamine in the brain, such as amphetamines, are known to cause psychosis, while drugs that treat psychosis do so by reducing dopamine activity.
In the study researchers examined hundreds of post-mortem specimen brains donated to the Lieber Institute from more than 350 people, some with schizophrenia and others without psychiatric illness.
The researchers found the mechanisms that make dopamine receptors a risk factor.
The mechanism exists specifically in a subtype of the dopamine receptor, called the autoreceptor, which regulates how much dopamine is released.
If autoreceptors are compromised, the flow of dopamine within the brain is poorly controlled, and too much dopamine flows for too long.
Decreased expression of this autoreceptor in the brain explains the genetic evidence of risk for illness, the scientists say.
Neuroscientist Dr Sol Snyder, who discovered that antipsychotic drugs work by reducing brain dopamine, hailed the study as a breakthrough many decades in the making.
He said: “There’s lots of muddled data indicating the relevance of dopamine and dopamine receptors in schizophrenia.
“The key thing these researchers have done is to collect data that puts it all together and in a fashion that is persuasive in establishing that dopamine systems are out of kilter in schizophrenia, and that is causal to the disease.
“For decades, people have debated the dopamine connection to schizophrenia.
“They used to say, ‘Well, this is interesting to speculate about, but there’s no solid evidence.’
“But now that we have much more rigorous data available, we keep coming back to the same story. You don’t have to call it a hypothesis anymore.”
Their findings are published in the journal Nature Neuroscience.