More than 25 million people world wide are affected by schizophrenia. Highly hereditable, it is one of the most severe mental illnesses with a high economic burden on countries worldwide.
Since Schizophrenia was first described over a century ago, it has long been among the most mysterious mental illness, with little known about the biological process that causes the brain to become schizophrenic during adolescence. Efforts to shed light on the condition have so far failed, leaving it very difficult to diagnose schizophrenia or create models for testing new drugs. Drug treatments currently available blunt some of the symptoms but are ineffective in touching the underlying cause.
A landmark study by researchers from the Broad Institute’s Stanley Centre for Psychiatric Research, Harvard Medical School, and Boston Children’s Hospital has made a major breakthrough in understanding a genetic link to the disorder, and therefore a potential molecular process that triggers schizophrenia in the brain. This study has answered many of the big questions surrounding the disorder such as suggesting a reason for the late adolescent development.
The cause
The study analysed the DNA of 100,000 people with schizophrenia from 30 different countries and aimed to locate regions of the human genome which harboured genetic variants that increased the risk of the disorder. The scientists uncovered that the gene variant C4 on chromosome 6 had a high degree of structural variability, meaning there can be a number of different types of the gene and copy numbers found in the population. They used this data to determine the C4 activity in the genomes of 65,000 people both with and without schizophrenia. The study showed a strong correlation between C4 and risk of schizophrenia, patients with a certain structural form of C4 showed higher expression of the gene and an increased risk of developing the disorder.
The effect
From these breakthrough results came more questions, most importantly, how does C4 cause the increased risk of developing schizophrenia? It was found that C4 plays an important role in pruning synapses which are no longer needed as the brain develops into adulthood. Despite this being a normal process, in schizophrenia it is believed that high expression of C4 causes too many cells to be targeted for elimination and a loss of grey matter in the brain.
These findings offer possible answers for longstanding questions surrounding schizophrenia. It may explain why the brains of people with schizophrenia have thinner cerebral cortices and fewer synapses than those who aren’t affected. And it may explain why the symptoms of schizophrenia tend to have an onset in late adolescence.
Looking forward
In addition to providing the first insights into the biological process behind schizophrenia, the findings provide hope for the development of a therapy which not only targets a few symptoms of schizophrenia but rather the conditions root causes. The aim is to be able to detect the disorder early, before the condition takes hold and start preventative treatment.
Just as importantly the research may go a long way to improve how the disease itself is perceived and may convince health systems to do more for those suffering. Currently, large number of people with schizophrenia are abandoned by our society and health care systems to homelessness and jail rather than being cared for in a proper way. Potentially, thanks to research such as this, schizophrenia and other biological illnesses will stop being trivialized as ‘mental health problems and issues’ and we can start seeing these conditions as the devastating biological illnesses they are.
It will likely be years before this recent genetic research can be developed into an effective treatment, but before that happens, attitudes towards this condition should start to change to improve how those currently suffering are treated.
Amy Cleaver
Image courtesy of Craig Finn, image hosted on Wikipedia.