Genetic tests could help predict which psychosis patients will develop schizophrenia

New research from King's College London suggests that genetic tests could one day help to predict which patients are most likely to develop schizophrenia after experiencing psychosis for the first time.

While there is no single change in a gene that is responsible for psychosis and schizophrenia, an increasing body of evidence suggests that hundreds or thousands of different genetic variants contribute to an individual’s risk of developing psychosis or schizophrenia.  

Each genetic variant has a subtle influence on an individual’s likelihood of developing psychosis, schizophrenia, or other mental illnesses, but collectively these genes have a substantial influence.  Research has also shown that, for people with schizophrenia, early treatment can greatly improve outcomes, so earlier confirmation of diagnoses could make a big difference to patients.

Because human traits are so complex and influenced by thousands of gene variants with very small individual effects, researchers have developed a way of assessing the joint effects of all of these trait-associated variants, called a “polygenic risk score”. The value of polygenic risk scores is that they allow researchers to estimate the genetic effects on mental illness, or any other trait, at an individual level, based on a person’s DNA.

The new findings, which are published in the journal Biological Psychiatry, show that a polygenic risk score for patients who are admitted to hospital after experiencing psychosis for the first time can partly predict who will go on to receive a diagnosis of schizophrenia, rather than recovering completely or being diagnosed with another mental disorder.

Dr Evangelos Vassos and colleagues from the MRC Social Genetic and Developmental Psychiatry Centre at King’s College London undertook genetic analyses of nearly 450 first-episode psychosis patients receiving treatment at South London & Maudsley NHS Foundation Trust, and over 250 healthy individuals.

The results showed that polygenic risk scores were able to explain around 10% of the risk of developing schizophrenia compared to developing other psychotic disorders or who recovering completely. The finding was replicated in a second sample of patients with a longer history of schizophrenia and other disorders.

Dr Vassos explains: “Although polygenic risk scores are unlikely to ever be powerful enough to screen the general population for their risk of developing schizophrenia, our findings indicate that they could potentially help clinicians, when used in combination with other evidence, in situations where a diagnosis is unclear.”

“Vast progress has been made recently in understanding the genetics of psychiatric and other complex disorders, but it has been unclear how genetics might be useful in the clinic,” adds Dr Gerome Breen, senior author of the study.  “This work clearly shows the potential of this approach - bringing ‘Polygenic Medicine’ to the clinic - and it is very exciting.”

The study also examined the genetic differences between people with different diagnoses and ethnicities, providing valuable insights for future work in this area, particularly in diverse areas such as south east London, where the Maudsley Hospital is located.

Study reference: http://dx.doi.org/10.1016/j.biopsych.2016.06.028


Tags: Publications - Precision psychiatry - BioResource - Clinical disorders and health behaviours - Psychosis & neuropsychiatry -

By NIHR Maudsley BRC at 27 Sep 2016, 12:19 PM


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