Implications

All precursors that were associated with persistence in our study were also associated with incidence of psychotic experience, whereas for almost all precursors examined, risk for transient experiences lay somewhere between that for no psychotic experiences and persistent psychotic experiences. Our findings provide little evidence to support the presence of specific disease-modifying factors, i.e. characteristics that have little impact on aetiology, but primarily affect severity after onset. Insights gained into aetiology and prevention strategies are therefore likely to be very similar, whether we want to prevent the onset of psychotic experiences or impede the persistence of these and subsequent transition to psychotic disorder over time. It is possible, however, that other measures not included in our study, such as proteomic, lipidomic or other biomarkers, might affect only persistence or severity rather than onset of psychotic phenomena, as has been described, albeit rarely, in other areas of medicine.^{Reference Onitilo, Engel, Glurich, Stankowski, Williams and Doi42}

Our results, if reflecting causal effects, suggest there might be multiple avenues for prevention of onset and persistence of psychotic experience, including treating childhood psychopathology and parasomnias, improving cognitive skills and emotional stability, and reducing exposure to trauma (for example, through parenting or bullying-reduction programmes^{Reference Chen and Chan43,Reference Gaffney, Ttofi and Farrington44} ) or addressing post-traumatic symptoms (for example, through trauma-focused therapies^{Reference van den Berg, de Bont, van der Vleugel, de Roos, de Jongh and Van Minnen45}). These highlight the importance of current initiatives aimed at early identification and treatment of mental health problems in children and young people. Furthermore, the constellation of characteristics (borderline traits, emotional instability, self-harm, nightmares and trauma history) associated with the high-frequency persistent psychotic experiences group indicates similarity to complex post-traumatic stress disorder, consistent with conceptualisations of psychotic disorders as complex manifestations of post-traumatic psychological mechanisms.^{Reference Hardy46}

In our study, over 75% of those with high-frequency persistent psychotic experiences met the ICD-10 criteria for an anxiety disorder or for moderate or severe depression at either age 18 or 24 years, compared with 44% of those with transient experiences, and the cumulative risk of these disorders is likely to have been even higher if we had measures of depression and anxiety that spanned the whole period from adolescence to early adulthood. Similarly, approximately 80 and 60%, respectively, of those with high-frequency and low-frequency persistent psychotic experiences had self-harmed by 24 years of age, highlighting that individuals with recurrent or persistent psychotic experiences represent a group of young people with a substantial need for clinical intervention or support.

It was not possible to determine the temporal relationship between the psychotic experience profiles and other psychopathology over the same time period, which may have facilitated inference of causality, although the strength of support for causal effects of most exposures that we examine here on psychotic experiences has previously been documented.^{Reference van Os, Linscott, Myin-Germeys, Delespaul and Krabbendam19,Reference Linscott and van Os47} Nevertheless, our findings suggest that the vast majority of those with high-frequency persistent psychotic experiences will have required help for other mental health problems at some stage, and thus there are likely to be opportunities for identifying and monitoring those who are at highest risk of developing a clinical psychotic disorder.^{Reference Sullivan, Kounali, Cannon, David, Fletcher and Holmans2,Reference Dominguez, Wichers, Lieb, Wittchen and van Os9,Reference Zammit, Kounali, Cannon, David, Gunnell and Heron11,Reference Hanssen, Bak, Bijl, Vollebergh and van Os12}

Strengths and limitations

This study has a number of strengths, including the use of prospectively assessed and often repeated measures of precursors and correlates of psychotic experience profiles, allowing for a more comprehensive examination of characteristics that discriminate between persistent and non-persistent experiences than previous studies. Ours is also the first study to use semi-structured interview measures to assess psychotic experiences, thus minimising information bias. Additionally, although previous studies (with one exception^{Reference Rossler, Riecher-Rossler, Angst, Murray, Gamma and Eich6}) examined trajectories over relatively short periods of time (2–6 years), our study is able to provide information on longer-term persistence of psychotic experiences over a timespan of more than 12 years, with our findings being similar when examining profiles at different developmental stages (ages 12–18 years and 18–24 years). Nevertheless, the findings described here must also be interpreted in the context of a number of limitations.

First, as with most other large cohort studies that span long periods of time, there was a substantial amount of missing data. To address this we used multiple imputation and included a large number of covariates to make the missing at random assumption more plausible; nevertheless, it remains possible that our results are affected by selection bias. Second, for variables included in our repeat-measure correlates, we were unable to tease out the direction of effect in relation to the psychotic experience profiles. However, the aim of our study was not to determine whether the associations we observed are likely to be causal or not, but to identify markers that characterise persistence of psychotic experiences once they occur, and which could potentially inform future studies of prediction of psychotic disorder. Third, although we examined a broad range of measures encompassing markers of sociodemographic status, genetic risk, psychopathology, cognition and behaviours in relation to psychotic experience profiles, we did not examine all cognitive or psychological constructs, or other biological or neuroimaging data.

Finally, we used an empirical approach rather than a latent model approach to derive our profiles of psychotic experiences over time, as, because of the small numbers in the non-zero classes, no latent model was sufficiently stable despite the size of our study. We utilised information on frequency and persistence of experiences to help create profiles to represent psychotic experience trajectories that were guided by our research questions; nevertheless, there may be some misclassification of individuals. Additionally, it would have been of interest to include information on distress in the derivation of the psychotic experience profiles as distress, as both distress and frequency are likely to index psychotic experience severity,^{Reference Fusar-Poli, Yung, McGorry and van Os48} but unfortunately this was not available at all assessments.

Summary

In this study, we identified a number of characteristics that differentiated between longitudinal profiles of psychotic experiences across adolescence and early adulthood, including other psychopathology, substance use, cognitive deficits and biases, personality traits and childhood trauma. There was little evidence, however, that any of these characteristics affected only the course rather than the onset of psychotic experiences, suggesting that it is the severity of exposure rather than specific disease-modifying factors that most strongly determines whether psychotic experiences are transient or persist over time.