Complex origins of disease revealed
At the core of the psychiatric dilemma has always been an inability to directly view the inner mechanisms that cause a person to act a certain way. Physical nicks and scrapes are visible, and their direct effects on the body are easy to chart – psychiatric disorders and illnesses of the mind are less simple.
To its credit, psychiatric science has come a long way.
Researchers at the Washington University School of Medicine (WUSM) in St. Louis, Missouri recently discovered that one of psychiatric medicine’s most notoriously difficult to diagnose and treat illnesses – schizophrenia – might just be the amalgamation of eight genetically distinct disorders.
The team was led by Dr. C. Robert Cloninger, the Wallace Renard Professor of Psychiatry and WUSM. Their findings were published in the American Journal of Psychiatry on Sept. 15, 2014.
The study analyzed 4200 individuals diagnosed with schizophrenia, 3800 control subjects, and almost 700,000 single nucleotide polymorphisms (SNPs) within the genome.
“Genes don’t operate by themselves,” said Dr. Cloninger, in a WUSM press release. “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.”
Schizophrenia is known to cause auditory and visual hallucinations, as well as feelings of paranoia and delusion. However, not every patient diagnosed with the illness shows every possible symptom. About 80 per cent of the risk for schizophrenia is known to be genetic, but medical science has been unable to isolate the individual genes that produced the illness. Up until now, medical experts assumed that the disease manifested itself in different ways, with certain patients experiencing different symptoms.
By studying individual cases of schizophrenia and comparing the genes of those suffering with the disease to those not diagnosed with the illness, Dr. Cloninger and his team were able to isolate symptoms with a percentage certainty of schizophrenia. For example, some patients with hallucinations or delusions had genetic variations that created a 95 per cent certainty of schizophrenia. Others had genetic variations that created a 100 per cent certainty of schizophrenia, and so forth.
“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.
In all, Dr. Cloninger and his team isolated and identified 42 clusters of genetic variations that increased the risk of schizophrenia.
“In the past, scientists had been looking for associations between individual genes and schizophrenia,” said Dr. Dragan Svrakic, co-investigator and professor of psychiatry at WUSM. “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 illness.”
Once the team was able to isolate clusters of variation, they were able to categorize and divide patients according to the type and severity of their symptoms. The results showed symptoms that correlated with eight genetically distinct disorders, all rooted in genetic causes.
Dr. Cloninger and his team’s results are exciting for two distinct reasons. First, for those suffering from “schizophrenia,” this research is a step towards better treatment and management of the disease. Finally, for those suffering from any type of mental illness, the team’s research is indicative of a strong need to rethink the way mental health is studied and researched.