Chuck Bednar for redOrbit.com – Your Universe Online
Schizophrenia is not a single disease, but a group of eight genetically distinct disorders – each with its own unique set of symptoms, according to new research published online Monday in The American Journal of Psychiatry.
Dr. C. Robert Cloninger, one of the senior investigators of the study as well as a professor of psychiatry and genetics at the Washington University School of Medicine in St. Louis, and his colleagues believe their findings could be the first step towards improving how the condition is diagnosed and treated.
According to the researchers, approximately 80 percent of schizophrenia risk is inherited, but scientists have struggled to identify the exact genes responsible for the debilitating psychiatric illness. Now, after conducting detailed analysis of genetic influences on over 4,000 people with schizophrenia, the study authors have identified distinct gene clusters which they said contribute to eight different classes of the disorder.
“Genes don’t operate by themselves. They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact,” Dr. Cloninger, whose team matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients, said in a statement.
The investigators looked at nearly 700,000 sites within the genome where a single DNA unit is changed, also known as a single nucleotide polymorphism (SNP), in 4,200 people with schizophrenia and 3,800 healthy controls. The goal was to discover how individual genetic variations interacted with one another in order to produce the illness.
For example, in some patients suffering from delusions or hallucinations, they matched distinct genetic features to the symptoms and demonstrated with 95 percent certainty the genetic variations that would have caused that type of schizophrenia. In a second group, they discovered a link between disorganized speech and behavior with a unique set of DNA variations that carried a 100 percent risk of schizophrenia.
“What we’ve done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the ‘orchestra’ is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia,” explained Dr. Cloninger.
While individual genes only have weak and somewhat inconsistent associations with the disease, groups of gene clusters that interact with each other can result in a 70 percent to 100 percent risk of developing schizophrenia. The study authors said that this makes it nearly impossible for people with those specific variations to avoid the condition. In all, they identified 42 clusters of genetic variations which dramatically increase schizophrenia risk.
“In the past, scientists had been looking for associations between individual genes and schizophrenia,” explained Dr. Dragan Svrakic, a study co-author and Washington University psychiatry professor. “When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don’t act independently. They work in concert to disrupt the brain’s structure and function, and that results in the illness.”
Dr. Svrakic noted that he and his colleagues were only able to see how these specific clusters of DNA variations acted together to cause specific types of symptoms once they were able to organize genetic variations and patients symptoms into groups. They then divided patients into groups based on the type and severity of their symptoms, including hallucinations and delusions, lack of initiative, and disconnect between thoughts and emotions.
In all, they developed symptom profiles that described eight qualitatively distinct disorders based on underlying genetic conditions. They also were able to replicate their findings using two additional DNA databases of schizophrenia patients, indicating that identifying the gene variations that are working together is a valid avenue for research and a possible way to improve diagnosis and treatment in the future.
“People have been looking at genes to get a better handle on heart disease, hypertension and diabetes, and it’s been a real disappointment,” Dr. Cloninger said. “Most of the variability in the severity of disease has not been explained, but we were able to find that different sets of genetic variations were leading to distinct clinical syndromes. So I think this really could change the way people approach understanding the causes of complex diseases.”
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