Course of psychotic symptoms, depression and global functioning in persons at clinical high risk of psychosis: Results of a longitudinal observation study over three years focusing on both converters and non-converters
Introduction
The clinical high-risk (CHR) state as a means to screen vulnerable persons at increased risk for manifest psychosis is now an established feature of modern evidence-based medicine. Thus far, most work has centred on the predictive validity of CHR criteria, related brain biomarkers and on estimates of conversion rates (for reviews see: Addington and Heinssen, 2012, Cannon, 2016, Fusar-Poli et al., 2013, Klosterkotter et al., 2011). These reviews concluded that the CHR approach is a promising prognostic tool aimed at detecting early prodromal signs in order to prevent onset of first episode psychosis. However, CHR screening in its present form has also been criticised on various grounds (Fusar-Poli et al., 2014, McGorry and Nelson, 2016, van Os and Murray, 2013). Critical issues particularly involve the discriminant and prognostic validity of CHR screening.
For instance, a study by Lin et al. (2011) over a mean observation period of 7.3 years found that among participants with the poorest functional outcome only 49% were converters. The remaining 51% of these severely impaired persons were thus non-converters. Ziermans et al. (2011) showed that youths meeting ultrahigh-risk (UHR) criteria were at least three times more likely to remit from their CHR status than to develop psychosis during a two-year follow-up. In addition, Schlosser et al. (2012) showed a conversion rate of 30% and a rate of 66% for symptomatic remission or functional recovery over a 2-year observation period, while Velthorst et al. (2011) reported a conversion rate of 26% contrasted with a rate of 56% for full remission over a three-year period. These findings indicate that full remission and recovery is the more likely outcome in CHR-positive subjects than a conversion to psychosis. Accordingly, over a three-year follow-up period the false-positive rate of psychosis based on a CHR-positive screening was estimated at 64%, suggesting that approximately two-thirds of CHR-positive subjects do not develop psychosis even over an extended timespan (Fusar-Poli et al., 2012). Although low conversion rates do not necessarily imply poor construct validity, they could nevertheless compromise the cost-benefit ratio of CHR screening and hence its public health significance. Moreover, a screening test's high false-positive rate compromises clinical utility when treatments carry the risk of severe side-effects and long-term consequences (Fusar-Poli and Schultze-Lutter, 2016). For instance, it is not clear whether mammography screening for breast cancer does more harm than good, as the ratio of positive (life prolonged) to negative consequences (unnecessary lumpectomy or mastectomy) is negative (Gotzsche and Nielsen, 2011).
To better gauge the utility (or possible risk) of CHR screening, it is necessary to focus on the course of symptoms in both converters and non-converters, as only a direct comparison allows for estimating what is actually at stake (hence, contrasting false-positive with true-positive diagnoses). Addington et al. (2011) examined the course of psychotic syndromes for non-converters over a 30-month follow-up period, but they did not contrast these symptom trajectories with the clinical outcome for converters. Concerning the discriminant validity of CHR screening, it has further been suggested that many conversions could be trivial and clinically irrelevant, which typically occurs when criteria for psychosis are liberal or arbitrary (Fusar-Poli et al., 2014, Yung et al., 2010). It has also been stressed that some persons assumed to be CHR are in fact already suffering some kind of first psychosis episode (Fusar-Poli et al., 2014, McGorry and Nelson, 2016). That is, specifically within converters there is possibly no clear delineation between the at-risk state and the onset of manifest psychosis. However, one can only critically address such questions when the outcomes of interest comprise the course of continuous measures of symptom severity rather than a rough distinction between psychotic and non-psychotic. To the best of our knowledge, no such test has been provided to date.
This is the first study, therefore, to focus on the course of psychotic symptoms, depression and global functioning over a three-year observation period in both converters and non-converters. The main objective was to examine whether symptom trajectories could provide evidence for discriminant validity, firstly, between converters and non-converters, and secondly, between CHR-state and manifest psychosis specifically within converters.
Section snippets
Participants and procedure
The “Early Recognition of High Risk of Bipolar Disorder and Psychosis” project is part of “The Zurich Program for Sustainable Development of Mental Health Services” (ZInEP) at the University Hospital of Psychiatry, Zurich. An information-campaign was launched in newspapers, magazines, brochures and flyers to raise awareness of early recognition of psychotic and bipolar disorders within the general public and among healthcare professionals. The majority of subjects were referred to the early
Results
We first tested whether sex, age, positive and negative psychotic symptoms, depressive symptoms as well as antipsychotic or anti-depressive medication at baseline (t0) predicted subsequent dropouts. The only predictor that significantly related to dropouts was baseline negative symptoms (b = 0.585, 95%-CI = 0.265–0.905, p < 0.001). However, and most importantly, missing value analysis based on maximum likelihood expectation-maximization revealed that all outcomes of interest met the criteria of MCAR
Discussion
Various original studies have examined the validity of clinical and neurobiological characteristics for the prediction of conversion rates (for comprehensive reviews see: Addington and Heinssen, 2012, Cannon, 2016, Fusar-Poli et al., 2013), but none has provided a detailed analysis of the longitudinal course of psychosis spectrum symptoms and other continuous clinical outcomes in both converters and non-converters. Therefore, we believe that this is the first paper on the course of psychotic
Conflict of interest
All authors declare no conflict of interest.
Contributors
MPH drafted the manuscript and conducted all analyses. He had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. AT and KH significantly contributed to writing of this manuscript and interpretation of the results. KH, DD, SW, WR and AT significantly contributed to study design and data acquisition. All authors revised the manuscript and approved the final version.
Role of funding source
This work was supported by a private donor that wants to remain anonymous. The sponsor had no further role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Acknowledgments
All authors declare no conflict of interest. This work was supported by a private donor who wants to remain anonymous. The sponsor had no further role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. MPH drafted the manuscript and conducted all analyses. He had full access to all the data in the study and takes responsibility for the
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2020, PsychoneuroendocrinologyPredictive validity of conversion from the clinical high risk syndrome to frank psychosis
2020, Schizophrenia ResearchCitation Excerpt :One key component of the CHR paradigm has received relatively little direct investigative attention: the criteria for conversion or transition to frank psychosis. While there is substantial evidence for the validity of the CHR converter designation as compared to non-converters (Sun et al., 2009; Takahashi et al., 2009; Walterfang et al., 2008; Wood et al., 2011; Yung et al., 2010; Yung et al., 2003), there has been relatively little attention to the predictive validity of the conversion assessment for clinical outcome over time (Hengartner et al., 2017) and in comparison to separate first episode samples. It is not sufficient that no CHR subjects receive psychosis diagnoses on Structured Interview for DSM (SCID) or that all CHR structured interview-defined psychosis subjects do (Woods et al., 2009), because the SCID and CHR judgments are generally not made independently in CHR research clinics.
Future directions in risk research
2020, Risk Factors for Psychosis: Paradigms, Mechanisms, and PreventionChecking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis
2017, European PsychiatryCitation Excerpt :The projected conversion rate was accordingly 17.5% (see Fig. 1). As detailed in a previous report [5], antipsychotic medication across the three-year observation period had no impact on the course of psychotic symptoms. The prognostic validity of various CHR criteria is shown in Table 2.