What causes schizophrenia has long baffled scientists. But in what is deemed the largest ever molecular genetic study of schizophrenia, a team of international researchers has pinpointed 108 genes linked to the condition – 83 of which are newly discovered – that may help identify its causes and pave the way for new treatments.
Schizophrenia is a mental health condition that affects approximately 24 million people worldwide. Although symptoms of the condition can vary, the most common are delusions, hallucinations, abnormal thoughts and agitated body movements.
Despite years of research, the exact causes of schizophrenia remain unclear. Study leader of this latest research Prof. Michael O’Donovan, of the Cardiff University School of Medicine in the UK, told Medical News Today that identifying the causes of schizophrenia is notoriously difficult.
“There are no ‘tests’ that allow to select patients that are likely to be very similar in their causes, which means we examine groups of people with probably multiple forms of the disorder, and this dilutes the relationships between risk factors and outcome,” he explained, adding:
“We can’t easily access the brain in a direct way to obtain tissue from living people, so studying the disorder through many traditional approaches in medicine is more difficult. And because the assessment is by interview and careful observation, recruiting large numbers of people into studies is more costly than for simpler, easier-to-diagnose conditions.”
However, recent studies have found that people with schizophrenia tend to have certain genetic mutations, which may play a part in its development.
For example, Medical News Today recently reported on a study by researchers from University College London in the UK, which detailed the discovery of a rare gene variant present in around 1 in every 200 people that may increase the risk of developing schizophrenia, as well as bipolar disorder and alcohol dependence.
Another study, by researchers from Johns Hopkins University School of Medicine in Baltimore, MD, detailed how one variation in a schizophrenia-related gene called 15q11.2 influences brain development.
In this latest study, Prof. O’Donovan and fellow researchers from the Schizophrenia Working Group of the Psychiatric Genomics Consortium – an international collaboration of more than 300 scientists set up in 2007 to conduct large-scale research into psychiatric disorders – uncovered an array of genetic risk factors for schizophrenia, shedding light on the condition’s biological cause.
To reach their findings, the researchers analyzed 36,989 genetic samples from people with schizophrenia, alongside genetic samples from 113,075 healthy individuals.
The analysis – results of which are published in the journal Nature – revealed 108 specific locations in the human genome linked to schizophrenia. Of these, 83 had not been previously associated with the condition.
The team found that many of these genes were expressed in brain tissue, some of which are related to the functioning of neurons and synapses – responsible for the electrical and chemical signaling between neurons. Furthermore, the team also found that some of the genes were expressed in the immune system, supporting previous theories that schizophrenia is associated with immunological mechanisms.
Prof. O’Donovan and colleagues at Cardiff University explain the findings in more detail in the video below:
Prof. O’Donovan notes that over the past 60 years, the development of new treatments for schizophrenia has “stalled.” Since the cause of the condition is unclear, current treatments – such as antipsychotic medications – focus on alleviating the symptoms.
But he hopes these latest findings will change this, particularly since the team’s research revealed that a gene called dopamine receptor D2 (DRD2) was linked to schizophrenia. This gene is responsible for the production of a protein that current schizophrenia medication can block.
Explaining the relevance of these findings, Prof. O’Donovan told Medical News Today:
“The fact that our study was able to identify a direct genetic link to the only known target for treatment suggests that proteins made by some of the other genes we identified may also themselves be therapeutic targets. So if we are lucky, there may be some short-term (5 years or so) benefits.
But even if those genes and the proteins they make themselves are not suitable or effective treatment targets, at a minimum, the wealth of findings provides a rational starting point for multiple avenues of investigation that are likely to deliver a much better understanding of the disorder, and it is then reasonable to hope, a new range of treatments.”
Prof. O’Donovan added that although these findings are exciting, they must not be interpreted. “Our study is a necessary, important, large step forward, but on its own is not sufficient,” he said.
However, he told us that this research does provide a solid foundation for neuroscientists to follow up:
“Genetics only provides pointers to aspects of biology, but other research is needed to follow up those pointers and translate that into a detailed understanding of disease mechanisms. So by providing lots of genetic clues, we have provided an unprecedented number of openings to study the biology of the disorder.”
And Prof. O’Donovan is sure that further research will uncover more genes linked to schizophrenia and bring us one step closer to the desired new and effective treatments for the condition.
“We need biologists and psychologists to do experiments to understand the relationships between the DNA changes and changes in gene function, how changes in gene function affect the proteins, and how changes in those proteins affect cells, tissues, and whole person function. That’s a lot of work,” he added, “but the process is started. That understanding is what’s really needed to convert the genetics to treatments.”
Core funding for this study was provided by the National Institute of Mental Health.