Study reveals new insights into genetic risk for psychotic experiences

Largest study of its kinds identifies shared genetic liability with multiple psychiatric disorders

A team of researchers led by Professors James Walters and Stanley Zammit at Cardiff University has found a shared genetic liability between psychotic experiences and psychiatric and neurodevelopmental disorders.

Professor Stanley Zammit, Professor of Psychiatric Epidemiology at the MRC Centre for Neuropsychiatric Genetics and Genomics said: “The risk factors and causes of psychotic experiences are unclear, as is the relationship between these experiences and schizophrenia or clinical psychosis.

“In this study, we have found evidence that supports a shared genetic liability between psychotic experiences and not only schizophrenia but also a broad range of other disorders including major depression, bipolar, ADHD and autism spectrum disorder.”

Up to 1 in 10 people report having a psychotic experience during their lifetimes. While these experiences can be different in nature, they often include hallucinations or delusions; believing that something is happening that isn’t based in reality or that others cannot understand.

The majority of people who report psychotic experiences do not have a clinical psychiatric disorder. Although they are key features of schizophrenia and some other conditions, they are only considered to be symptomatic of illness if they have had a negative impact on someone’s level of functioning, and are present with other symptoms, like difficulty concentrating or feeling less motivated.

Using data from the UK Biobank, researchers compared genetic markers between over 6,000 people who reported having a psychotic experience, but no diagnosis of a psychotic disorder or schizophrenia, and more than 120,000 people who did not report any psychotic experiences.

The team identified genetic variants within two genes, ANK3 and CRN2, had an association with psychotic experiences. Crucially, a number of previous studies have identified an association between these genes and a range of psychiatric disorders.

Dr Sophie Legge, a postdoctoral research fellow at the MRC Centre said: “ANK3 is one of the strongest and most replicated genes linked with bipolar disorder, and variants within this gene have been associated with autism spectrum disorder.

“In addition, the association with CRN2 adds support to the role of the cannabinoid system in psychotic experiences, although the underlying mechanisms behind this association are still unclear.”

Professor James Walters, Professor of Psychiatry at the MRC Centre, added: “These results tell us that there is some genetic contribution to the risk of psychotic experiences and that this genetic contribution is shared with a broad range of clinical mental health conditions, and not specifically with schizophrenia.

“However, further work is needed to understand how these genes affect the risk of someone having a psychotic experience and to understand the biological mechanism that causes these types of experiences

The paper, ‘Association of genetic liability to psychotic experiences with neuropsychiatric disorders and traits’ is published open access in JAMA Psychiatry.