Findings from a large genome-wide association study indicated that genetic liability of psychotic experiences may be shared with several psychiatric disorders in addition to schizophrenia, including major depressive disorder, bipolar disorder and neurodevelopmental disorders.
Prior genome-wide association studies indicate that psychotic experiences in adolescence may specifically increase the risk for schizophrenia later in life; however, epidemiologic evidence also suggests a possible nonspecific increased risk for broader psychopathologic characteristics, Sophie E. Legge, PhD, of the MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, U.K., and colleagues wrote in JAMA Psychiatry.
Researchers performed analyses of genetic correlation, polygenic risk scores and copy number variation using data from participants in the UK Biobank to determine whether genetic liability to psychotic experiences was shared with schizophrenia and/or other neuropsychiatric disorders and traits. They also conducted genome-wide association studies to identify novel genetic loci tied to psychotic experience phenotypes.
Analyses included 6,123 individuals reporting any psychotic experience, 2,143 reporting distressing psychotic experiences, 3,337 reporting multiple occurrences of psychotic experiences, and 121,843 comparators (i.e. individuals who did not report a psychotic).
Legge and colleagues reported that psychotic experiences were genetically associated with MDD, schizophrenia, autism spectrum disorder and ADHD. Also, analyses of polygenic risk scores indicated correlations between psychotic experiences and genetic liability for MDD, schizophrenia, bipolar disorder, autism spectrum disorder, and ADHD.
“However, given the possibility of sample overlap between the UK Biobank and the training sets, the [polygenic risk score] findings should be treated with caution,” the researchers wrote.
The results showed that participants who reported psychotic experiences showed a greater burden of copy number variations tied to schizophrenia (OR = 2.04; 95% CI, 1.39-2.98) and neurodevelopmental disorders (OR = 1.75; 95% CI, 1.24-2.48). Furthermore, according to the genome-wide association studies, four novel genetic loci were tied to psychotic experience phenotypes, including a locus in Ankyrin-3 (OR = 1.16; 95% CI, 1.1-1.23) and a locus in cannabinoid receptor 2 gene (OR = 0.66; 95% CI, 0.56-0.78).
“The combination of environmental and genetic composite scores may lead to improved insight into individualized pathways toward psychotic experiences, highlighting genetic vulnerabilities to specific stressors likely to lead to phenotypic expression,” Albert R. Powers III, MD, PhD, from the Connecticut Mental Health Center at Yale University School of Medicine, wrote in a related editorial.
“Ultimately, this will require a more sophisticated mapping between phenomenology and biology than currently exists,” he continued. “To enable this, genetic approaches should be combined with deep phenotyping and behavioral analysis within a theoretical framework capable of linking all relevant explanatory levels, from symptom expression to neurophysiology.” – by Savannah Demko
Disclosures: Three authors reported a grant from Takeda Pharmaceuticals; no other authors report any relevant financial disclosures. Powers reports support from the Burroughs-Wellcome Fund, the NIMH and the Yale University School of Medicine and department of psychiatry.