Objective: To investigate the incidence, course and outcome of psychotic experiences from childhood through early adulthood in the general population, and prediction of psychotic disorder.Methods: A population-based cohort study using the semi-structured Psychosis-like Symptoms interview of psychotic experiences at ages 12, 18, and 24 (N=7900 with any data). Incidence rates were estimated using flexible parametric modelling, and positive predictive values (PPV), sensitivity, specificity, and area under the curve estimated for prediction. Results:The incidence rate of psychotic experiences increased between ages 13-24 years, peaking during late adolescence. Of 3866 interviewed at age 24, 313 (8.1%, 95%CI 7.2%, 9.0%) had a definite psychotic experience since age 12. 109 individuals (2.8%) met criteria for a psychotic disorder up to age 24, of whom 70% had sought professional help.Prediction of current psychotic disorder at age 24 (N=47, 1.2%) by both self-report and interviewerrated measures of psychotic experiences at age 18 (PPVs 2.9% and 10.0% respectively) was improved by incorporating information on frequency and distress (PPVs 13.3% and 20.0% respectively), although sensitivities were low. The PPV of an at-risk mental state at age 18 predicting incident disorder ages 18-24 was 21.1% (95%CI 6.1%-45.6%; sensitivity 14.3%, 95%CI 4.0%-32.7%). Conclusions:Our study shows a peak in incidence of psychotic experience during late adolescence, and an unmet need for care in young people with psychotic disorders. Because of the low sensitivity, targeting individuals in non-help-seeking samples based only on more severe symptom cut-off thresholds will likely have little impact on population-levels of first-episode psychosis.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. This publication is the work of all authors and SZ will serve as guarantor for the contents of this paper.

A recent development in the genetic architecture of schizophrenia suggested that an omnigenic model may underlie the risk for this disorder. The aim of our study was to use polygenic profile scoring to quantitatively assess whether a number of experimentally derived sets would contribute to the disorder above and beyond the omnigenic effect. Using the PGC2 secondary analysis schizophrenia case-control cohort (N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.

Background Psychotic experiences are reported by 5–10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance. Aims To investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors. Method Using data from 8045 individuals from a birth cohort study, longitudinal profiles of psychotic experiences based on semi-structured interviews conducted at 12, 18 and 24 years were defined. Environmental, cognitive, psychopathological and genetic determinants of these profiles were investigated, along with concurrent changes in psychopathology and cognition. Results Following multiple imputations, the distribution of longitudinal profiles of psychotic experiences was none (65.7%), transient (24.1%), low-frequency persistent (8.4%) and high-frequency persistent (1.7%). Individuals with high-frequency persistent psychotic experiences were more likely to report traumatic experiences, other psychopathology, a more externalised locus of control, reduced emotional stability and conscientious personality traits in childhood, compared with those with transient psychotic experiences. These characteristics also differed between those who had any psychotic experiences and those who did not. Conclusions These findings indicate that the same risk factors are associated with incidence as with persistence of psychotic experiences. Thus, it might be that the severity of exposure, rather than the presence of specific disease-modifying factors, is most likely to determine whether psychotic experiences are transient or persist, and potentially develop into a clinical disorder over time.