TORONTO – Little is known about the causes of schizophrenia, but an international consortium of researchers has made a significant discovery about its genetic underpinnings that should improve understanding of this devastating mental illness.
Scientists from around the world, including Canadians, have identified more than 100 locations in the human genome associated with the risk of developing schizophrenia, a brain disorder characterized by hallucinations, delusions and disordered thinking.
The research, published Tuesday in the journal Nature, pinpoints 83 newly discovered locations of genetic variations in the DNA of people with schizophrenia, bringing the number known to 108.
“It gives us a whole new avenue for research,” said Jo Knight, a senior scientist at the Centre for Addiction and Mental Health in Toronto, who was part of the research group.
“It’s like being handed a huge haystack in which we know there are a whole bunch of needles,” she said Monday. “We’ve just been given a haystack and now we have to find all the needles. But we know they’re in there and we know now this is the haystack to be looking in.”
Those needles are genetic mutations that give rise to schizophrenia, which often emerges in the teens and early 20s and affects one in every 100 people worldwide. The price tag of health care, social costs and lost productivity resulting from the debilitating mental illness is estimated at $6.85 billion a year in Canada alone.
Knight said there are many theories as to why someone might be susceptible to developing schizophrenia, which is believed to be caused by a combination of many genes as well as environmental triggers.
The new findings implicate genes expressed in brain tissue, particularly those related to the functioning of neurons and the pathways that enable chemical and electrical signalling between these brain cells, known as synapses.
They also give weight to a theory that genes active in immune-system functioning may also be involved with schizophrenia, suggesting that it could be an autoimmune disease, at least in part.
“When you start getting at the genetic architecture, you start having much more of an understanding of the pathology,” said Knight. “And once you know why someone is becoming schizophrenic, you’re much more likely to be able to develop a drug to act on the mechanism or develop preventive measures that stop an individual following that route.”
The study follows several years of work by the Schizophrenia Working Group of the Psychiatric Genomics Consortium, an international collaboration founded in 2007 to conduct broad-scale analyses of genetic data for psychiatric disease.
In the study, the authors looked at almost 37,000 genetic samples from schizophrenia patients and about 113,000 healthy volunteers and found 108 specific locations in the human genome associated with the risk of schizophrenia.
“The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases,” said senior study author Dr. Michael O’Donovan, deputy director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine.
“The wealth of new findings has the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years,” O’Donovan said in a release, referring to the lack of new drugs for the disorder in the last six decades.
Taryn Tang, manager of research at the Schizophrenia Society of Ontario, called the study “a huge and impressive undertaking.”
“Schizophrenia is one of the most debilitating mental illnesses, so any work and certainly a work of this magnitude is great in that we are providing new hope and possibilities for improved understanding and care for patients,” said Tang, who was not involved in the research.
She said that while antipsychotic drugs can help control such symptoms as auditory and visual hallucinations, they have no effect on so-called “negative” symptoms, such as lack of motivation, cognitive deficits and memory loss. Antipsychotics can also cause a number of unpleasant side-effects, among them weight gain and persistent muscle spasms.
“So people who live with schizophrenia not only hear voices and have belief systems that you or I might not, but they can’t get out of bed to go to their doctor,” said Tang. “They can’t get a job or hold down a job. They can’t be independent and earn income for themselves. They can’t remember to take their medication or are not motivated to take their medication regularly. They can’t hold down social relationships — so all of the things that give life meaning really.”
While it’s accepted wisdom that the cause of schizophrenia is multifaceted — likely a melding of genetic makeup and various environmental triggers — the findings of the genomic study provide a good jumping-off point for further investigating the disease, she said.
“This is a start. What we would like to see is moving this knowledge into practice, for the clients and their families who are looking for real-world solutions,” said Tang, adding that new drugs are needed to improve functioning in concert with psychological therapies aimed at easing apathy and other negative symptoms.
Knight said that although the study won’t immediately change the lives of those with schizophrenia or their loved ones, it should spur renewed hope that research will at some point provide a breakthrough in treating the disease.