Abstract
Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10−4) and rs9960767 (p-value = 6.23×10−4). Replication in an independent sample of 16-year-olds (N = 3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed.
Highlights
The notion of the psychosis continuum postulates that psychosis is a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder are its extreme manifestations [1]
Females scored significantly higher than males on Cognitive Disorganisation and males scored significantly higher than females on Grandiosity, Anhedonia and Parent-rated Negative Symptoms (p,0.001)
This is further supported by the evidence from a number of genetic association studies and a twin study, which show that symptom variation within clinical psychosis is partly influenced by ‘modifier genes’(genes that influence clinical features of a disease but not its liability) [38,39], which might influence adolescent psychotic experiences
Summary
The notion of the psychosis continuum postulates that psychosis is a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder are its extreme manifestations [1] (see [2]). High scores on psychotic experiences in childhood (age 11) were shown to be an indication of an increased risk of developing a psychotic disorder later in life (age 26)[4]. It is typically not until adolescence/early adulthood that psychotic symptoms first emerge [6] and the association between psychotic experiences and a number of psychiatric disorders strengthens [7]. The predictive power of these psychotic experiences for a number of psychiatric disorders strengthened with an increase in age These findings highlight the potential value of studying psychotic experiences in midadolescence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
